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1
Murray, Shannon. "Foamy virus-host interactions /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/4987.
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Hütter, Sylvia, Irena Zurnic, and Dirk Lindemann. "Foamy Virus Budding and Release." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127060.
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Like all other viruses, a successful egress of functional particles from infected cells is a prerequisite for foamy virus (FV) spread within the host. The budding process of FVs involves steps, which are shared by other retroviruses, such as interaction of the capsid protein with components of cellular vacuolar protein sorting (Vps) machinery via late domains identified in some FV capsid proteins. Additionally, there are features of the FV budding strategy quite unique to the spumaretroviruses. This includes secretion of non-infectious subviral particles and a strict dependence on capsid-glycoprotein interaction for release of infectious virions from the cells. Virus-like particle release is not possible since FV capsid proteins lack a membrane-targeting signal. It is noteworthy that in experimental systems, the important capsid-glycoprotein interaction could be bypassed by fusing heterologous membrane-targeting signals to the capsid protein, thus enabling glycoprotein-independent egress. Aside from that, other systems have been developed to enable envelopment of FV capsids by heterologous Env proteins. In this review article, we will summarize the current knowledge on FV budding, the viral components and their domains involved as well as alternative and artificial ways to promote budding of FV particle structures, a feature important for alteration of target tissue tropism of FV-based gene transfer systems.
3
Hartl, Maximilian Johannes. "Foamy virus enzymes : activity, regulation and resistance." kostenfrei, 2009. http://opus.ub.uni-bayreuth.de/volltexte/2010/676/.
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Eastman, Scott Walton. "The mechanisms of foamy virus capsid assembly /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/11516.
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Meiering, Christopher David. "The complexity of persistent foamy virus infection /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/11527.
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Stenbak, Carolyn Rinke. "Foamy virus polymerase : enzymatic activities and assembly /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/11510.
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Patton, Gillian Sarah. "Production and application of foamy virus-derived vectors." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429910.
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Russell, Rebecca Alice. "Prototype foamy virus gene expression and hybrid vector development." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408262.
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Sweeney, Nathan Paul. "Foamy virus vector integration and application in gene therapy." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/50704.
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Foamy viruses (FVs) are unique ancient retroviruses that infect all non-human primates, but do not cause disease. We aimed to understand the FV pre-integration complex by isolating it from infected cells and characterising its protein constituents. Using a PCR to quantify integration in infected cells, we determined that integration occurs from 10 hours post-transduction. In synchronised cells, the peak of integration correlated well with cells passing through mitosis. However, we were unable to detect in vitro strand-transfer activity to indicate that active pre-integration complexes had been isolated. We conclude that FV pre-integration complexes are likely to be inactive in the conditions tested. A further aim was to optimise FV vectors for use in mesenchymal stem cells and test this vector in mouse models of sphingolipidoses, namely metachromatic leukodystrophy and Krabbe disease. We permitted transduction of cells at a high multiplicity of infection by exchanging the envelope from the prototype FV to that of the macaque. We tested various FV vectors in mesenchymal stem cells and determined that the non-toxic macaque envelope increased transduction efficiency from under 65% to over 95% in a single round of transduction. We achieved high and sustained transgene expression using the phosphoglycerate kinase promoter. Transduced MSCs delivered to the brains of the mouse model for metachromatic leukodystrophy caused only a modest improvement in sulphatide storage, the primary biochemical output for efficacy, although results are inconclusive. In the mouse model for Krabbe disease, transduced MSCs delivered to the brain or the peritoneum had no effect on disease progression. In conclusion, FV vectors are suited to gene therapy of MSCs since they offer the highest transduction efficiency from a single round of transduction, while MSC based gene therapy strategies for Krabbe disease or metachromatic leukodystrophy are unlikely to offer clinical benefit.
10
Renault, Noémie. "Trafic intracellulaire de la protéine Gag du virus Foamy." Paris 7, 2009. http://www.theses.fr/2009PA077154.
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Les virus foamy sont des rétrovirus complexes qui appartiennent à la famille des spumaviridae. Ces rétrovirus présentent de nombreuses particularités qui les différencient des orthorétrovirus comme l'existence d'ADN viral infectieux dans la particule virale ou celle d'un ARNm codant pour la polyprotéine Pol, ou encore l'absence d'un facteur de régulation post-transcriptionnelle de type Rev ou Rex. De la même manière, les protéines Gag ne présentent pas les caractéristiques fondamentales retrouvées chez les autres rétrovirus comme le clivage en matrice, capside et nucléocapside. Nous avons focalisé notre travail sur ces protéines structurales et sur leurs rôles tant lors des étapes précoces que tardives. Lors des étapes précoces, la polyprotéine Gag protège le génome viral et le guide sur le réseau microtubulaire jusqu'à la membrane nucléaire. Dans les cellules qui cyclent, les particules,virales enfantes du virus foamy sont retrouvées intactes au centrosome à partir de 4 h post-infection. La capside subit alors un désassemblage en partie dépendant de la protéase virale. A l'inverse, dans les cellules quiescentes, nous montrons que les capsides restent structurées autour centrosome. A la reprise du cycle cellulaire, le cycle réplicatif viral reprend avec le déshabillage de la capside et l'intégration du provirus. Les protéases cellulaires et virales, qui interviennent lors de la décapsidation, semblent ainsi inactives lorsque les cellules sont en phase GO. De manière non exclusive, les sites de clivage de ces protéases sur les protéines structurales du virus pourraient être inaccessibles dans ces conditions. Les protéines Gag jouent également un rôle clé lors des étapes tardives de l'infection, en étant responsables de l'assemblage des capsides qui a lieu dans le cytoplasme, autour du centrosome. De manière intéressante, avant l'assemblage, ces protéines transitent dans le noyau. Nous nous sommes intéressés à cette étape nucléaire et montrons que la protéine Gag est exportée du noyau grâce à un signal d'export nucléaire riche en leucine et sensible à la leptomycine B, présent dans la partie N-terminale de la protéine. Une protéine Gag mutée dans ce domaine est non seulement incapable de quitter le noyau mais interfère négativement avec la réplication d'un virus sauvage. Nous suggérons que les protéines Gag des virus foamy pourraient intervenir dans l’export nucléaire de l’ARN viral lors des étapes tardives de l'infectionFoamy viruses (FVs) are complex exogenous animal retroviruses that differ in many aspects of their life cycle from the orthoretroviruses such as human immunodefîciency virus (HIV). In particular, in FVvs, Gag and Pol proteins are expressed independently of one another, and both proteins undergo single clivage events. None of the conventional Gag landmarks of exogenous retroviruses, such as the major homology region or Cys-His motifs, are found in this protein. Instead, FV Gag harbors conserved C-terminal basic motifs, referred to as Gly-Arg (GR) boxes. Although the first GR (GRI) box binds viral nucleic acids and is required for viral genome packaging, the second (GRII) harbors a nuclear localization sequence (NLS) at its C-terminus, targeting Gag to the nucleus early after infection. GRII also contains a chromatin binding sequence (CBS) in its N-terminus, tethering the FV incoming pre-integration complex onto host chromosomes. The present work focuses on the structural Gag proteins, in early and late stages of infection. Troviral Gag proteins are involved in early stages of infection such as trafficking of incoming viruses nd nuclear import. FV Gag protein uses the microtubule network to reach the nucleus. In cycling cells,FV articles are structured at the centrosome 4 h post-infection. Then, the viral protease helps capsid for ncoating. In quiescent cells, we have shown that viral particles remain structured at the centrosome during everal weeks and that uncoating does not occur : this step is a limiting factor for infection although viral articles are still infectious. Upon cells reactivation, viral capsids undergo proteolysis and disassembly, llowing infection to proceed. During the late stages of infection, Gag undergoes transient nuclear trafficking after it synthesis, before returning back to the cytoplasm for capsid assembly and virus egress. The functional role of this nuclear stage, as well as the molecular mechanisms responsible for Gag nuclear export, are not understood. Here, we identify a leptomycin-sensitive nuclear export sequence (NES) within the N-terminus of the primate foamy virus Gag protein that is absolutely required for the completion of late stages of virus replication. Point mutation of conserved residues within this motif leads to nuclear retention of Gag and dramatically affects viral replication. Moreover, complementation experiments demonstrate that nuclear export-defective Gag mutants negatively interfere with virus release by sequestering wild-type Gag in the nucleus
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Lehmann-Che, Jacqueline. "Etudes des étapes précoces de l'infection des virus foamy." Paris 7, 2006. http://www.theses.fr/2006PA077126.
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Dans le cycle réplicatif des rétrovirus, les étapes tardives de l'infection ont été élucidées ces dernières années alors que les étapes précoces, allant de l'entrée du virus jusqu'à l'intégration du génome dans celui de la cellule hôte, restent encore peu connues. Par le présent travail, nous avons tenté de répondre à un certain nombre de questions concernant ces étapes cruciales en prenant les rétrovirus foamv comme modèle. A l'aide d'un virus mutant pour la protéase virale, nous avons impliqué pour la première fois, cette enzyme dans le processus de décapsidation d'un rétrovirus. Ainsi la protéase assure le clivage des protéines Gag du core viral entraînant sa déstructuration et l'exposition en surface des signaux de localisation nucléaire permettant un import nucléaire du complexe de préintégration. Dans un modèle de cellules arrêtées en phase GO du cycle cellulaire, nous avons mis en évidence que l'absence de déshabillage des particules virales rend compte du défaut réplicatif dans ces cellules. Il semble que l'étape de décapsidation puisse être une étape limitante à l'origine de l'inefficacité de l'infection dans les cellules quiescentes. Nous avons également identifié une séquence dans Gag responsable d'un ancrage du PIC au chromosome de la cellule infectée qui peut être impliquée dans le maintien et/ou le ciblage de l'intégration. La compréhension précise de ces étapes semble indispensable à l'amélioration des vecteurs de transfert de gène appliqués aux cellules quiescentes et post-mitotigues mais également à la maîtrise de l'intégration rétrovirale dans le génome hôte conduisant à l'utilisation raisonnée des rétrovirus en tant gué vecteurs de transfert de gèneAlthough retroviral egress and buddinq have been partly unraveled little is known on earlv stages of the replication cycle. In particular, retroviral uncoating a process during which incoming retroviral cores are progressively modified to allow integration of the viral genome into host chromosomes is poorly understood. To get insights into these early events of the retroviral cycle, foamy viruses (FVs) were used as a model. In the present work, we provide strong evidence that FV uncoating depends on the proteolytic activity of the viral protease. A protease-defective virus is still able to bud efficiently, to enter thé target œil, and to reach the centrosome (IWTOC) but remain noninfectious. In the mutant virus, uncoating is altered and leads to the accumulation of uncoated capsids at the centrosome. Interestingly, a similar situation was observed following infection of resting cells by wild-type virus. Therefore, virus uncoating. Likely involving the viral protease, is the limiting stage in such cells. Finally, we also identified a stretch of basic 13 amino-acids in the structural Gag protein displaying efficient chromosome tethering properties, contrlbuting to integration site specificitv or/and maintenance of unintegrated DMA genome during mitosis. Understanding precisely these early stages is essentiel to discover new therapeutic approaches and to generate efficient and safer therapeutic vectors for gene therapy
12
Tanaka, Elly M., Dirk Lindemann, Tatiana Sandoval-Guzmán, Nicole Stanke, and Stephanie Protze. "Foamy virus for efficient gene transfer in regeneration studies." BioMed Central, 2013. https://tud.qucosa.de/id/qucosa%3A28877.
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Background
Molecular studies of appendage regeneration have been hindered by the lack of a stable and efficient means of transferring exogenous genes. We therefore sought an efficient integrating virus system that could be used to study limb and tail regeneration in salamanders.
Results
We show that replication-deficient foamy virus (FV) vectors efficiently transduce cells in two different regeneration models in cell culture and in vivo. Injection of EGFP-expressing FV but not lentivirus vector particles into regenerating limbs and tail resulted in widespread expression that persisted throughout regeneration and reamputation pointing to the utility of FV for analyzing adult phenotypes in non-mammalian models. Furthermore, tissue specific transgene expression is achieved using FV vectors during limb regeneration.
Conclusions
FV vectors are efficient mean of transferring genes into axolotl limb/tail and infection persists throughout regeneration and reamputation. This is a nontoxic method of delivering genes into axolotls in vivo/ in vitro and can potentially be applied to other salamander species.
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Tanaka, Elly M., Dirk Lindemann, Tatiana Sandoval-Guzmán, Nicole Stanke, and Stephanie Protze. "Foamy virus for efficient gene transfer in regeneration studies." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-176868.
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Background
Molecular studies of appendage regeneration have been hindered by the lack of a stable and efficient means of transferring exogenous genes. We therefore sought an efficient integrating virus system that could be used to study limb and tail regeneration in salamanders.
Results
We show that replication-deficient foamy virus (FV) vectors efficiently transduce cells in two different regeneration models in cell culture and in vivo. Injection of EGFP-expressing FV but not lentivirus vector particles into regenerating limbs and tail resulted in widespread expression that persisted throughout regeneration and reamputation pointing to the utility of FV for analyzing adult phenotypes in non-mammalian models. Furthermore, tissue specific transgene expression is achieved using FV vectors during limb regeneration.
Conclusions
FV vectors are efficient mean of transferring genes into axolotl limb/tail and infection persists throughout regeneration and reamputation. This is a nontoxic method of delivering genes into axolotls in vivo/ in vitro and can potentially be applied to other salamander species.
14
Berka, Ursula, Martin Volker Hamann, and Dirk Lindemann. "Early Events in Foamy Virus - Host Interaction and Intracellular Trafficking." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127078.
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Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.
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Mackler, Randi Michelle. "Understanding Prototype Foamy Virus Integrase Site Selection, Activity, and Stability." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1542306356468134.
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Lindemann, Dirk, Ursula Berka, and Martin Volker Hamann. "Early Events in Foamy Virus - Host Interaction and Intracellular Trafficking." MDPI, 2013. https://tud.qucosa.de/id/qucosa%3A28912.
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Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.
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Lindemann, Dirk, Ursula Berka, and Martin Volker Hamann. "Early Events in Foamy Virus - Host Interaction and Intracellular Trafficking." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-178848.
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Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.
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Lüftenegger, Daniel. "Einfluss posttranslationaler Modifikationen auf die Funktion des Prototyp Foamy Virus Hüllproteins." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1207905094649-72075.
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Die Familie der Retrovirinae wird in zwei Unterfamilien untergliedert, die Orthoretrovirinae und die Spumaretrovirinae. Foamyviren stellen aufgrund einiger besonderer Eigenschaften die einzigen Vertreter dieser Unterfamilie, die sie als Bindeglied zwischen den Retroviren und den Hepadnaviren erscheinen lassen. So erfolgt beispielsweise die reverse Transkription des viralen Genoms nicht erst nach Eintritt in die Zielzelle, sondern, anders als bei Orthoretroviren, bereits in der Produzentenzelle noch während oder kurz nach der Morphogenese. Diese Eigenschaft teilen Foamyviren mit den Hepadnaviren ebenso wie die obligate Koexpression der Kapsidproteine mit den viralen Hüllproteinen für die Freisetzung von Viruspartikeln. Im Gegensatz zu Orthoretroviren sind Foamyviren folglich nicht in der Lage virusähnliche Partikel (VLP) zu sekretieren und die spezifische Funktion des PFV Env Proteins kann nicht durch heterologe Hüllproteine übernommen werden. Die Synthese des PFV Env Vorläuferproteins erfolgt am rER, wobei es eine Typ III Membrantopologie erhält, mit sowohl dem N- als auch dem C-Terminus im Zytoplasma. Während des Transports des Proteins zum Ort der Partikelknospung, wird es posttranslational im Golgi-Apparat, oder dem trans-Golgi Netzwerk, durch Furin oder eine Furin-ähnliche Protease in drei partikelassoziierte Untereinheiten prozessiert. Eine Partikelassoziation retroviraler Signalpeptide ist bislang nur für Foamyviren nachgewiesen worden, genauso wie eine essentielle Rolle dieses Proteins bei der Interaktion zwischen dem
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Cain, Dionne Marie. "Aspects of foamy virus replication : dimerisation and the role of BET." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314185.
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Menon, Dev Christophe. "The development of prototypic foamy virus as a gene therapy vector." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506165.
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Prototypic foamy virus (PFV)-based vectors are currently made by transient transfection. Continuous vector production by cells in which PFV proteins are stably led would allow rapid, reproducible generation of large quantities of vector. Previous attempts at constructing packaging cell lines have resulted in very low titre production. Here, we utilise a method described to generate a stable HIV-1 producing cell-line in an attempt to produce high titres of PFV vector. PFV gag-pol or env genes were stably transduced into a variety of cell lines using an MLV-based delivery system. The resultant cell lines were positive for stable DNA integration and for high levels of protein expression, and produced between 10³ and 10⁵ infectious units of PFV vector. However the cells gradually reduced protein production which finally ceased completely after 4-5 weeks, possibly due to cytotoxicity.
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Baldwin, David Norris. "The mechanisms of Pol expression and assembly for human foamy virus /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/11509.
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Lüftenegger, Daniel. "Einfluss posttranslationaler Modifikationen auf die Funktion des Prototyp Foamy Virus Hüllproteins." Doctoral thesis, Technische Universität Dresden, 2007. https://tud.qucosa.de/id/qucosa%3A23754.
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Die Familie der Retrovirinae wird in zwei Unterfamilien untergliedert, die Orthoretrovirinae und die Spumaretrovirinae. Foamyviren stellen aufgrund einiger besonderer Eigenschaften die einzigen Vertreter dieser Unterfamilie, die sie als Bindeglied zwischen den Retroviren und den Hepadnaviren erscheinen lassen. So erfolgt beispielsweise die reverse Transkription des viralen Genoms nicht erst nach Eintritt in die Zielzelle, sondern, anders als bei Orthoretroviren, bereits in der Produzentenzelle noch während oder kurz nach der Morphogenese. Diese Eigenschaft teilen Foamyviren mit den Hepadnaviren ebenso wie die obligate Koexpression der Kapsidproteine mit den viralen Hüllproteinen für die Freisetzung von Viruspartikeln. Im Gegensatz zu Orthoretroviren sind Foamyviren folglich nicht in der Lage virusähnliche Partikel (VLP) zu sekretieren und die spezifische Funktion des PFV Env Proteins kann nicht durch heterologe Hüllproteine übernommen werden. Die Synthese des PFV Env Vorläuferproteins erfolgt am rER, wobei es eine Typ III Membrantopologie erhält, mit sowohl dem N- als auch dem C-Terminus im Zytoplasma. Während des Transports des Proteins zum Ort der Partikelknospung, wird es posttranslational im Golgi-Apparat, oder dem trans-Golgi Netzwerk, durch Furin oder eine Furin-ähnliche Protease in drei partikelassoziierte Untereinheiten prozessiert. Eine Partikelassoziation retroviraler Signalpeptide ist bislang nur für Foamyviren nachgewiesen worden, genauso wie eine essentielle Rolle dieses Proteins bei der Interaktion zwischen dem
23
Lecellier, Charles-Henri. "Etude des mécanismes moléculaires responsables de la persistance des virus foamy." Paris 7, 2004. http://www.theses.fr/2004PA077112.
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Lambert, Caroline. "Les anticorps neutralisants contre l'infection des virus foamy simiens chez l'homme." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC328/document.
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Les virus foamy simiens (VFS) sont la troisième famille des rétrovirus complexes exogènes infectant l'Homme. Ces virus, zoonotique, sont transmis par des fluides biologiques (principalement la salive), lors d'un contact direct entre un individu et un singe infecté. Ils établissent une infection chronique chez l'hôte infecté. À ce jour, aucune pathologie n'a été associée à au cas d'infections humaines par le VFS, et aucun cas de transmission secondaire n'a été rapporté dans la population. L'infection VFS représente un modèle naturel de la restriction de l'émergence d'un rétrovirus simien chez l'Homme. Lors de ma thèse, j'ai caractérisé la réponse humorale contre les VFS chez des personnes vivant au Cameroun ou au Gal infectées suite à des morsures lors d'épisodes de chasse. J'ai montré la présence d'anticorps neutralisants les VFS dans 48 sujets infectés, à des titres élevés. La population étudiée est infectée par des virus de deux génotypes qui diffèrent dans le domaine central de la protéine impliqué dans la liaison au récepteur cellulaire. J'ai montré des réponses neutralisantes spécifiques de chaque génotype des sujets étudiés et des réactivités croisées chez 40% d'entre-eux. Parmi ces derniers, la moitié est infectée par deux souches virales. En conclusion, mon travail de thèse est la première caractérisation des anticorps neutralisants chez des personnes infectées chroniquement par un VFS zoonotique : ces anticorps sont fréquemment détectés, à des titres élevés et sont dirigés contre des épitopes conservés entre les VFS de chimpanzé et de gorilleSimian foamy virus (SFV) are the third family of exogenous complex retroviruses infecting humans. These viruses, of origins, are transmitted by body fluids (mainly saliva), through a direct contact between an individual and an infected m establish a chronic infection in the infected human host. To date, neither pathology, nor secondary transmission has be to be associated with SFV infection in humans. Therefore, SFV represents a natural model of restriction emerging simiar in humans. During my PhD, I characterized the humoral response against SFV in people living in Cameroon and Gabon, mainly infected bites during hunting episodes. I showed the presence of SFV neutralizing antibodies in the plasma of 48 infected individ titers. Our study population is infected with viruses of 2 different genotypes, which differ in the central region of the En region involved in binding to the cellular receptor.While in 60% of cases, neutralizing response was specific to a single genotype, 40% of cases showed cross-reactivity. Cr( was associated in 50% of cases with co-infection with viruses from both genotypes.In conclusion, my PhD is the first study to characterize neutralizing antibodies in individuals chronically infected with a zoonotic SFV : these antibodies are frequently detected at high titers and are directed against epitopes commonly found in chimpanzee and gorilla SFV
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Ruboyianes, Ryan, and Michael Worobey. "Foamy-like endogenous retroviruses are extensive and abundant in teleosts." OXFORD UNIV PRESS, 2016. http://hdl.handle.net/10150/624082.
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Recent discoveries indicate that the foamy virus (FV) (Spumavirus) ancestor may have been among the first retroviruses to appear during the evolution of vertebrates, demonstrated by foamy endogenous retroviruses present within deeply divergent hosts including mammals, coelacanth, and ray-finned fish. If they indeed existed in ancient marine environments hundreds of millions of years ago, significant undiscovered diversity of foamy-like endogenous retroviruses might be present in fish genomes. By screening published genomes and by applying PCR-based assays of preserved tissues, we discovered 23 novel foamy-like elements in teleost hosts. These viruses form a robust, reciprocally monophyletic sister clade with sarcopterygian host FV, with class III mammal endogenous retroviruses being the sister group to both clades. Some of these foamy-like retroviruses have larger genomes than any known retrovirus, exogenous or endogenous, due to unusually long gag-like genes and numerous accessory genes. The presence of genetic features conserved between mammalian FV and these novel retroviruses attests to a foamy-like replication biology conserved for hundreds of millions of years. We estimate that some of these viruses integrated recently into host genomes; exogenous forms of these viruses may still circulate.
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Müller-Hermelink, Maya. "Verwandlung eines komplexen Retrovirus in ein einfaches am Beispiel des Foamy Virus." kostenfrei, 2008. http://nbn-resolving.de/urn/resolver.pl?urn=nbn:de:bvb:20-opus-26755.
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Blasse, Anja [Verfasser]. "Modalities of Transmission of Simian Foamy Virus in Wild Chimpanzees / Anja Blasse." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1060044854/34.
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Lindemann, Dirk, Kristin Stirnnagel, Daniel Lüftenegger, Annett Stange, Anka Swiersy, Erik Müllers, Juliane Reh, et al. "Analysis of Prototype Foamy Virus particle-host cell interaction with autofluorescent retroviral particles." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-176566.
Full textAbstract:
Background
The foamy virus (FV) replication cycle displays several unique features, which set them apart from orthoretroviruses. First, like other B/D type orthoretroviruses, FV capsids preassemble at the centrosome, but more similar to hepadnaviruses, FV budding is strictly dependent on cognate viral glycoprotein coexpression. Second, the unusually broad host range of FV is thought to be due to use of a very common entry receptor present on host cell plasma membranes, because all cell lines tested in vitro so far are permissive.
Results
In order to take advantage of modern fluorescent microscopy techniques to study FV replication, we have created FV Gag proteins bearing a variety of protein tags and evaluated these for their ability to support various steps of FV replication. Addition of even small N-terminal HA-tags to FV Gag severely impaired FV particle release. For example, release was completely abrogated by an N-terminal autofluorescent protein (AFP) fusion, despite apparently normal intracellular capsid assembly. In contrast, C-terminal Gag-tags had only minor effects on particle assembly, egress and particle morphogenesis. The infectivity of C-terminal capsid-tagged FV vector particles was reduced up to 100-fold in comparison to wild type; however, infectivity was rescued by coexpression of wild type Gag and assembly of mixed particles. Specific dose-dependent binding of fluorescent FV particles to target cells was demonstrated in an Env-dependent manner, but not binding to target cell-extracted- or synthetic- lipids. Screening of target cells of various origins resulted in the identification of two cell lines, a human erythroid precursor- and a zebrafish- cell line, resistant to FV Env-mediated FV- and HIV-vector transduction.
Conclusions
We have established functional, autofluorescent foamy viral particles as a valuable new tool to study FV - host cell interactions using modern fluorescent imaging techniques. Furthermore, we succeeded for the first time in identifying two cell lines resistant to Prototype Foamy Virus Env-mediated gene transfer. Interestingly, both cell lines still displayed FV Env-dependent attachment of fluorescent retroviral particles, implying a post-binding block potentially due to lack of putative FV entry cofactors. These cell lines might ultimately lead to the identification of the currently unknown ubiquitous cellular entry receptor(s) of FVs.
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Leo, Berit [Verfasser], and Birgitta [Akademischer Betreuer] Wöhrl. "Foamy Virus RNase H - Aktivität, Struktur und Funktion / Berit Leo. Betreuer: Birgitta Wöhrl." Bayreuth : Universität Bayreuth, 2013. http://d-nb.info/1059352982/34.
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Lindemann, Dirk, Kristin Stirnnagel, Daniel Lüftenegger, Annett Stange, Anka Swiersy, Erik Müllers, Juliane Reh, et al. "Analysis of Prototype Foamy Virus particle-host cell interaction with autofluorescent retroviral particles." BMC, 2010. https://tud.qucosa.de/id/qucosa%3A28868.
Full textAbstract:
Background
The foamy virus (FV) replication cycle displays several unique features, which set them apart from orthoretroviruses. First, like other B/D type orthoretroviruses, FV capsids preassemble at the centrosome, but more similar to hepadnaviruses, FV budding is strictly dependent on cognate viral glycoprotein coexpression. Second, the unusually broad host range of FV is thought to be due to use of a very common entry receptor present on host cell plasma membranes, because all cell lines tested in vitro so far are permissive.
Results
In order to take advantage of modern fluorescent microscopy techniques to study FV replication, we have created FV Gag proteins bearing a variety of protein tags and evaluated these for their ability to support various steps of FV replication. Addition of even small N-terminal HA-tags to FV Gag severely impaired FV particle release. For example, release was completely abrogated by an N-terminal autofluorescent protein (AFP) fusion, despite apparently normal intracellular capsid assembly. In contrast, C-terminal Gag-tags had only minor effects on particle assembly, egress and particle morphogenesis. The infectivity of C-terminal capsid-tagged FV vector particles was reduced up to 100-fold in comparison to wild type; however, infectivity was rescued by coexpression of wild type Gag and assembly of mixed particles. Specific dose-dependent binding of fluorescent FV particles to target cells was demonstrated in an Env-dependent manner, but not binding to target cell-extracted- or synthetic- lipids. Screening of target cells of various origins resulted in the identification of two cell lines, a human erythroid precursor- and a zebrafish- cell line, resistant to FV Env-mediated FV- and HIV-vector transduction.
Conclusions
We have established functional, autofluorescent foamy viral particles as a valuable new tool to study FV - host cell interactions using modern fluorescent imaging techniques. Furthermore, we succeeded for the first time in identifying two cell lines resistant to Prototype Foamy Virus Env-mediated gene transfer. Interestingly, both cell lines still displayed FV Env-dependent attachment of fluorescent retroviral particles, implying a post-binding block potentially due to lack of putative FV entry cofactors. These cell lines might ultimately lead to the identification of the currently unknown ubiquitous cellular entry receptor(s) of FVs.
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Delelis, Olivier. "Un nouveau modèle de replication retrovirale : exemple des spumavirus." Paris 6, 2004. http://www.theses.fr/2004PA066083.
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ROZAIN, FRANCIS. "Identification et caracterisation des proteines d'un isolat humain de spumaretrovirus, le virus foamy hfv." Paris 7, 1993. http://www.theses.fr/1993PA077098.
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Nous avons demontre que les composantes extracellulaire (su) et transmembranaire (tm) des proteines d'enveloppe de hfv sont deux glycoproteines de 70 et 48 kd et que le precurseur des proteines d'enveloppe est la gp130. Quant a la gp160, elle possede des sequences propres aux proteines env et bel. Nous avons mis en evidence une proteine de 62 kd essentiellement cytoplasmique pouvant correspondre a la proteine bet car reconnue par des anticorps specifiques des proteines bel1 et bel2. Cette proteine, detectee aussi dans le noyau des cellules infectees et dans leur surnageant de culture, est la seule a etre maintenue au cours des infections latentes etablies in vitro. Ces donnees pourraient lui conferer un role regulateur. La presence des precurseurs gag p72 et p68 dans le cytoplasme des cellules infectees ainsi que dans les particules virales pourrait etre due a un defaut d'activite de la protease virale. Un clivage partiel se produit cependant apres un temps relativement important de contact du virus avec la cellule cible. Le clivage des precurseurs gag mais aussi de la proteine bet a pu etre obtenu par traitement a la dnase a force ionique elevee. Cela laisse supposer que des interactions existent entre ces proteines et l'adn proviral pouvant masquer certains sites d'action de la protease dont l'activite augmente avec la force ionique
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Richard, Léa. "Détection et caractérisation moléculaire des rétrovirus d'origine simienne chez l'Homme : cas du virus foamy et du virus T-lymphotrope de type 4." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC211/document.
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Les primates non-humains (PNH) sont un important réservoir de pathogènes et notamment de rétrovirus. Plusieurs agents infectieux ont émergé dans la population humaine à partir de ce réservoir animal, comme par exemple le virus de l’immunodéficience humaine ou le virus T lymphotrope humain (HTLV) de type 1 qui se sont répandus mondialement et causent de graves pathologies. L’émergence de rétrovirus chez l’Homme nécessite plusieurs étapes passant par la transmission primaire du virus du PNH à l’Homme, la persistance du virus dans l’organisme,la transmission secondaire inter-humaine et enfin sa diffusion dans la population. Mes deux projets de thèse ont porté sur l’étude de deux rétrovirus qui ont un potentiel d’émergence chez l’Homme, le virus foamy simien (SFV) et le virus T-lymphotrope de type 4, dans des cohortes d’individus à risque vivant au Cameroun et au Gabon. Les SFV sont des rétrovirus ubiquitaires chez de nombreux PNH. Plus d’une centaine de cas d’infection d’humains par des SFV ont été observés à ce jour, l’origine étant un contact(principalement par morsure) avec un PNH. L’infection est chronique et semble asymptomatique.De plus, aucune transmission secondaire n’a été détectée à ce jour. Le laboratoire a pu isoler, chez deux individus camerounais, deux souches de SFV de gorille et a constaté une forte variabilité génétique au niveau du gène d’enveloppe. Nous avons donc étudié la variabilité du gène d’enveloppe de SFV de gorille mais également de chimpanzé infectant une soixantaine de chasseurs camerounais et gabonais et une trentaine de PNH. Nous avons pu mettre en évidence la co-circulation de souches de SFV présentant des variants moléculaires du gène d’enveloppe différents chez les gorilles et les chimpanzés. Ces mêmes souches peuvent être transmises à l’Homme à l’occasion de morsures, les deux variants pouvant être transmis simultanément. Ces variants diffèrent au niveau d’une région de 753 pb située dans la région codant la glycoprotéine de surface, au niveau du domaine de liaison au récepteur. Ils pourraient ainsi avoir des propriétés fonctionnelles différentes, notamment au niveau de l’élicitation de la réponse immunitaire de l’hôte. Ces variants sont potentiellement issus d’événements de recombinaison.HTLV-4 a été détecté chez un unique individu, un chasseur camerounais, aujourd’hui décédé.En 2014, le réservoir simien a été identifié comme étant les gorilles. Nous avons recherché la présence de HTLV-4 chez 300 individus camerounais et gabonais qui avaient été mordus par un PNH. Nous avons identifié deux chasseurs gabonais infectés par HTLV-4, qui avaient été mordus par des gorilles 9 à 15 ans avant d’être prélevés. Nous confirmons donc la présence de HTLV-4 infectant de manière persistante des humains et étendons sa répartition au Gabon. Nous suggérons très fortement une origine zoonotique de ces infections. L’une des souches isolées est divergente par rapport aux souches déjà connues et permet donc de définir le sous-type B deHTLV-4.Ces travaux confortent la notion que les PNH, et notamment les gorilles, sont une source importante d’agents infectieux pour l’Homme. Des études supplémentaires seront nécessaires pour mieux caractériser l’infection chez l’Homme et notamment l’éventuelle pathogénicité et transmissibilité de ces deux virusNon-human primates (NHPs) are an important reservoir of pathogens, including retroviruses. Several retroviruses have emerged in human population from NHP reservoir, like the human immunodeficiency virus and the human T-lymphotropic virus type 1 who have spread globally and are the causative agents of serious pathologies. During my PhD, I interested in two retroviruses who have an emerging potential in human population, the simian foamy virus (SFV) and the human T-lymphotropic virus type 4 (HTLV-4), in cohorts of individuals at risk in Central Africa. SFV are retroviruses ubiquituous in NHPs. A hundred of human infections with SFV are known, originating from contacts with NHP. The infection is chronic, asymptomatic although no secondary transmission has been observed yet. We showed that two envelope molecular variants of SFV are co-circulating in gorilla and chimpanzee populations. These strains can be transmitted to humans through bites. The variants differ in the receptor binding domain on the envelope and could have different functional properties. HTLV-4 had been detected in a single individual (a cameroonese hunter) and the simian reservoir idenfied as gorillas. We have detected two gabonese hunters infected with HTLV-4, who had been bitten by gorillas. Then we confirm the presence of HTLV-4 in humans in Central Africa. One of the strains is divergent and defines the prototype of a new subtype of HTLV-4
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McNichol, Ryan Matthew. "Characteristics of a Foamy Virus-Derived Vector that allow for safe Autologous Gene Therapy to correct Leukocyte Adhesion Deficiency Type 1." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1189781066.
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German, Allison Christina. "Investigations into feline foamy virus and its development as a vector for gene therapy applications in the cat." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407030.
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Han, Guanzhu. "Paleovirology: Using Endogenous Retroviruses Within Animal Genomes To Understand The Deep History Of Retroviruses." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/338758.
Full textAbstract:
Retroviruses infect a wide range of vertebrates. The understanding of the deep history and host distribution of retroviruses remains far from complete. Retroviruses can be integrated into their host genomes and occasionally become vertically inherited genomic loci. These integrated retroviruses, known as endogenous retroviruses (ERVs), provide "molecular fossils" for past retroviral infections and are useful for studying the deep history and ecology of retroviruses. ERVs are highly abundant in vertebrate genomes. However, endogenous foamy viruses and lentiviruses appear to be extremely rare. The primary focus of the research presented here is to discover and analyze novel endogenous foamy viruses and lentiviruses in animal genomes. Foamy virus has been thought to exclusively infect three placental mammal superorders (Laurasiatheria, Euarchontoglires, and Xenarthra). The discovery of endogenous foamy viral elements (CoeEFV) in the genome of the coelacanth (Latimeria chalumnae) extends the host range of foamy viruses to fish lineages (Appendix A). I demonstrate that foamy viruses have likely codiverged with their vertebrate hosts for more than 407 million years. The discovery of CoeEFV provides evidence for an ancient marine origin of retroviruses. Endogenous foamy virus-like elements (PSFVaye) were also identified within the genome of a Malagasy lemur, the aye-aye (Daubentonia madagascariensis) (Appendix B). Phylogenetic analysis shows that PSFVaye is divergent from all currently known simian foamy viruses, suggesting a potentially ancient association between foamy viruses and primate species. Another novel endogenous foamy virus (CaEFV) was identified in the genome of the Cape golden mole (Chrysochloris asiatica). The discovery of CaEFV reveals foamy virus infection in the placental mammal superorder Afrotheria and the long-term cospeciation between foamy viruses and placental mammals (Appendix C). Lentivirus has been thought to have a relatively recent origin. Endogenous lentivirus insertions (MELV) were discovered within the genomes of some species of the Weasel family (Mustelidae) (Appendix D). I verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, which suggests that the lentiviral invasion likely occurred between 8.8 and 11.8 million years ago. Phylogenetic analysis suggests MELV might represent a novel lentiviral group. The discovery of MELV extends the host range of lentiviruses to the Caniformia. Endogenous lentiviruses (GvaELV) were also identified in the genome of the Sunda flying lemur (Galeopterus variegatus) (Appendix E). Phylogenetic analysis shows that GvaELV is a sister group of all known lentiviruses. The discovery of GvaELV might give a clue to the early evolution of lentiviral genome architecture. In summary, the discoveries and analyses of these novel ERVs provide important insights into the deep history and ecology of foamy viruses and lentiviruses as well as the retroviruses as a whole.
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Jaoui, Fatima-Zahra. "Etudes sur les relations entre l'interferon et le prototype humain des spumaretrovirus : hfv (human foamy virus) induction et sensibilite." Paris 5, 1996. http://www.theses.fr/1996PA05S027.
Full textAbstract:
Les spumavirus ou virus spumeux (foamy virus) constituent un des sept genera de la famille taxonomique des retroviridae. Ils comportent un genome complexe avec des genes additionnels de regulation et se caracterisent par leur capacite a induire un effet cytopathogene (ecp) singulier en culture de tissus. In vivo, s'ils ne semblent donner lieu chez leur hotes naturels a aucune entite nosologique specifique, ces virus determinent tres souvent des infections chroniques et latentes. Cependant, jusqu'a present leur implication directe dans une pathologie donnee n'a pu etre demontree. Dans ce contexte, nous avons etudie, in vitro, les interrelations entre hfv et l'interferon (ifn) dans des lignees d'origine differente : epitheliale, neurale, lymphocytaire et monocytaire. Nous avons ainsi demontre que hfv n'induit pas, au cours des infections aigue et chronique, de production d'ifn. Le virus est, toutefois, au cours d'une infection aigue, tres sensible a l'action de l'ifn recombinant humain qui inhibe son ecp, reduit le taux de transcriptase inverse present dans les surnageants des cultures traitees, et diminue tres fortement le nombre de particules observables par microscopie electronique. Le mecanisme d'action de l'ifn sur hfv semble s'exercer, alors, par blocage des syntheses initiales de l'adn proviral, ce qui conduit a l'inhibition des arn specifiques du virus et de ses polypeptides. Dans le cas d'infection chronique de cellules lymphocytaires t4 (lignee h9), la production virale est egalement bloquee tres efficacement par l'ifn. Cette inhibition semble dependre d'un mecanisme d'action post-integration de l'adn proviral. L'effet de l'ifn sur hfv, en infection aigue est assez proche de celui exerce sur hiv-1. Cette action antivirale semble differente de celle decrite pour les retrovirus de type b, c, et d, qui se situe au niveau du bourgeonnement et de la liberation des virions. En resume, nous avons demontre au cours de notre etude, que des preparations hautement purifiees d'ifn humain peuvent inhiber le cycle replicatif du hfv au cours d'une infection aigue ou chronique. Au dela de l'interet fondamental de ces donnees, nous rappellerons que les spumaretrovirus pourraient etre associes a certaines entites pathologiques humaines et que, dans ce cas, l'ifn pourrait representer un espoir therapeutique.
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Beasley, Miranda L. "Developing a Model System to Probe Biological Mechanisms of Post-Translational Modifications that Destabilize the Nucleosome." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1408961013.
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Ekstedt, Elias, Inna Fryckstedt, Hanna Hyllander, Josefin Jonsson, Elin Ring, and Felix Wærn. "The future of viral vectors for gene therapy." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-444138.
Full textAbstract:
Gene therapy is a fast growing technology that offers treatments for genetic diseases. The method is based on introducing genetic material into a patient to replace the disease-causing gene, using a vector. This report examines the potential of some viral vectors for gene therapy, to give Bio-Works Technologies a recommendation on what the future market demands. Oncolytic viruses, vaccines and gene editing are not treated in the report as a delimitation. Viral vectors have different biological properties and require different purification methods, making them suitable for different applications in gene therapy. In the purification of the viruses it can be challenging to obtain a high purity and large-scale manufacturing. One major drawback with most purification methods is that they are not specific to just one virus, which leads to contaminants in the solution and lower purity. The viral vectors handled in the report are the adenovirus, adeno-associated virus, gammaretrovirus, lentivirus, alpharetrovirus, foamy virus, herpes simplex virus and baculovirus. These were chosen as they are relevant vectors for gene therapy and stay within the scope of the report. Lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) will dominate the gene therapy field in the coming years. This is based on the information that the use of AAVs and LVs in clinical trials have increased in recent years, while the other vectors mentioned above have slightly decreased or show no apparent change. However, challenges still remain in the purification processes. Ligands used in affinity chromatography for purification of AAVs are effective at removing most contaminants, but cannot distinguish between empty and loaded capsids, which can induce immune response when used clinically. This is the main challenge when purifying AAVs. The empty capsids can be removed with ion exchange chromatography, which results in higher purity but also lower recovery. There is no specific purifying method for LVs, therefore a lentivirus-specific affinity ligand, such as an antibody ligand, would be beneficial for the purification and manufacturing procedure. In addition to AAVs and LVs, baculoviral vectors and foamy viral vectors show great potential in a long-term perspective but they only have been researched in preclinical studies. Moreover, herpes simplex viral vectors and adenoviral vectors show potential in cancer treatments or as vaccines rather than in augmentation gene therapy.
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Reh, Juliane, Annett Stange, Anne Götz, Marlene Rönitz, Arend Große, and Dirk Lindemann. "An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127152.
Full textAbstract:
Background: Foamy viruses (FVs) have developed a unique budding strategy within the retrovirus family. FV release requires co-expression and a highly specific interaction between capsid (Gag) and glycoprotein (Env), which cannot be complemented by heterologous Env proteins. The interaction domain in FV Env has been mapped in greater detail and resides mainly in the N-terminal tip of the cytoplasmic domain of the Env leader peptide subunit. In contrast, the corresponding domain within Gag is less well defined. Previous investigations suggest that it is located within the N-terminal part of the protein.
Results: Here we characterized additional Gag interaction determinants of the prototype FV (PFV) isolate using a combination of particle release, GST pull-down and single cycle infectivity analysis assays. Our results demonstrate that a minimal PFV Gag protein comprising the N-terminal 129 aa was released into the supernatant, whereas proteins lacking this domain failed to do so. Fine mapping of domains within the N-terminus of PFV Gag revealed that the N-terminal 10 aa of PFV Gag were dispensable for viral replication. In contrast, larger deletions or structurally deleterious point mutations in C-terminally adjacent sequences predicted to harbor a helical region abolished particle egress and Gag – Env protein interaction. Pull-down assays, using proteins of mammalian and prokaryotic origin, support the previous hypothesis of a direct interaction of both PFV proteins without requirement for cellular cofactors and suggest a potential direct contact of Env through this N-terminal Gag domain. Furthermore, analysis of point mutants within this domain in context of PFV vector particles indicates additional particle release-independent functions for this structure in viral replication by directly affecting virion infectivity.
Conclusions: Thus, our results demonstrate not only a critical function of an N-terminal PFV Gag motif for the essential capsid - glycoprotein interaction required for virus budding but also point out additional functions that affect virion infectivity.
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Reh, Juliane, Annett Stange, Anne Götz, Marlene Rönitz, Arend Große, and Dirk Lindemann. "An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity." BioMed Central, 2013. https://tud.qucosa.de/id/qucosa%3A27282.
Full textAbstract:
Background: Foamy viruses (FVs) have developed a unique budding strategy within the retrovirus family. FV release requires co-expression and a highly specific interaction between capsid (Gag) and glycoprotein (Env), which cannot be complemented by heterologous Env proteins. The interaction domain in FV Env has been mapped in greater detail and resides mainly in the N-terminal tip of the cytoplasmic domain of the Env leader peptide subunit. In contrast, the corresponding domain within Gag is less well defined. Previous investigations suggest that it is located within the N-terminal part of the protein.
Results: Here we characterized additional Gag interaction determinants of the prototype FV (PFV) isolate using a combination of particle release, GST pull-down and single cycle infectivity analysis assays. Our results demonstrate that a minimal PFV Gag protein comprising the N-terminal 129 aa was released into the supernatant, whereas proteins lacking this domain failed to do so. Fine mapping of domains within the N-terminus of PFV Gag revealed that the N-terminal 10 aa of PFV Gag were dispensable for viral replication. In contrast, larger deletions or structurally deleterious point mutations in C-terminally adjacent sequences predicted to harbor a helical region abolished particle egress and Gag – Env protein interaction. Pull-down assays, using proteins of mammalian and prokaryotic origin, support the previous hypothesis of a direct interaction of both PFV proteins without requirement for cellular cofactors and suggest a potential direct contact of Env through this N-terminal Gag domain. Furthermore, analysis of point mutants within this domain in context of PFV vector particles indicates additional particle release-independent functions for this structure in viral replication by directly affecting virion infectivity.
Conclusions: Thus, our results demonstrate not only a critical function of an N-terminal PFV Gag motif for the essential capsid - glycoprotein interaction required for virus budding but also point out additional functions that affect virion infectivity.
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Stange, Annett. "Determinanten und Mechanismen der foamyviralen Partikelfreisetzung." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1210174421492-57147.
Full textAbstract:
Die Spumaretrovirinae, mit ihrer einzigen Gattung der Foamyviren (FV), nehmen aufgrund einer recht ungewöhnlichen Replikationsstrategie und Ähnlichkeiten mit den Hepadnaviren eine Sonderstellung innerhalb der Familie der Retroviren ein. Eine Besonderheit der FV ist, daß sie für die Partikelfreisetzung, im Gegensatz zu den Orthoretroviren, die beiden strukturellen Proteine Gag und Env benötigen. Das Gag- Protein trägt alle für den Kapsidzusammenbau nötigen strukturellen Komponenten, kann jedoch durch eine fehlende Membranbindungsdomäne nicht mit Zellmembranen assoziieren. Der Membrantransport der bereits im Zytoplasma zusammen gebauten FV Kapside wird vermutlich durch das FV Env-Protein vermittelt. Das FV Hüllprotein ist jedoch auch alleine zur Freisetzung von Kapsidlosen, Hüllprotein-haltigen subviralen Partikeln (SVP) fähig. Da eine Envunabhängige Freisetzung virus-ähnlicher Partikel durch ein FV Gag-Protein mit künstlichem Membrananker möglich ist, scheint das FV Gag-Protein auch essentielle strukturelle Elemente für die Partikelfreisetzung zu enthalten. In den letzten Jahren wurden große Fortschritte in der Erforschung der Freisetzung von membranumhüllten Viren und den daran beteiligten viralen Determinanten und zellulären Mechanismen gemacht. Wobei den meist in den viralen Kapsidproteinen vorkommenden Late (L)-Domänen und deren Interaktion mit dem zellulären Proteinsortierungsweg in Multivesikuläre Körperchen (MVB) eine besondere Bedeutung zu kommt. Über die FV virale und subvirale Partikelfreisetzung und die dabei involvierten strukturellen viralen Domänen und zellulären Proteinen war jedoch bisher wenig bekannt. Im Rahmen dieser Arbeit konnte durch Mutationsanalysen von drei potentiellen L-Domän Sequenzmotiven im Prototyp FV (PFV) Gag-Protein ein, innerhalb der Primaten FV konserviertes, PSAP Konsensusmotiv als funktionelle L-Domäne charakterisiert werden. Dessen Mutation führte zu klassischen L-Domän Defekten mit verringerter Partikelfreisetzung, sowie einer elektronenmikroskopisch sichtbaren Arretierung der Virusknospung und seine Funktion war durch homo- und heterologe L-Domän Motive anderer Retroviren teilweise oder vollständig ersetzbar. Ein PPPI Motiv in PFV Gag, mit Ähnlichkeit zur L-Domän PPXY Konsensussequenz, schien jedoch keinen Einfluß auf die FV Freisetzung zu besitzen. Die Charakterisierung eines in allen FV Gag-Proteinen konservierten YXXL Motivs ließ eher auf eine wichtige Rolle beim korrekten Kapsidzusammenbau, als auf eine klassische LDomän Funktion schließen. Eine korrekte Kapsidmorphogenese schien entscheidend für die reverse Transkription des Virusgenoms zu sein. Durch Koexpression verschiedener dominant-negativer Mutanten des zellulären ESCRT-Proteinssortierungsweges konnte gezeigt werden, daß die virale Partikelfreisetzung von PFV augenscheinlich dem generellen Model der Freisetzung vieler membranumhüllter Viren über das VPS-System folgt. Eine spezifische Interaktion des PFV Gag PSAP L-Domän Motivs mit TSG101, einer frühen Komponente der ESCRT-Komplexe, verbindet PFV mit dem VPS-Sortierungsweg der Zelle. Die besondere Fähigkeit des FV Env-Proteins zur Freisetzung von SVPs wurde bereits vor einiger Zeit entdeckt, dennoch war bisher nichts über die viralen und zellulären Determinanten bekannt, die zu einer Knospung des Env-Proteins in Vesikel führten. Durch eine Reihe von Deletions- und Mutationsanalysen des PFV Env-Proteins konnten in dieser Arbeit zwei für die SVP-Freisetzung inhibitorische Abschnitte am N- und C-Terminus der zytoplasmatischen Domänen des Env- Proteins ermittelt werden. Weiterhin wurden essentielle Sequenzen im Leaderpeptid, sowie die Notwendigkeit der Membranspannenden Domäne der Transmembran- Untereinheit für die SVP-Freisetzung festgestellt. Obwohl das PFV Env-Protein kein bekanntes L-Domän Sequenzmotiv enthält, konnte ein Einfluß später Komponenten der ESCRT-Maschinerie auf die SVP-Bildung beobachtet werden. Wobei die genaue Eintrittsstelle in den VPS-Weg im Rahmen dieser Arbeit nicht definiert werden konnte. Die vorgenommen Analysen lassen vermuten, daß die Bildung von SVPs durch die Konzentration der Env-Proteine in der Zellmembranen reguliert wird. Welche genauen Mechanismen dabei zu Grunde liegen und wieweit die zelluläre Ubiquitinylierungsmaschinerie involviert ist, bedarf jedoch weiterer Erforschung. Die Ergebnisse dieser Arbeit verdeutlichen erneut die Sonderstellung der FV innerhalb der Familie der Retroviren. Auf der einen Seite folgt die foamyvirale Viruspartikelfreisetzung den typischen Mechanismen der retroviralen Virusknospung. Andererseits zeigt die Freisetzung von subviralen Partikeln, die bei keinem anderen Retrovirus bisher beobachtet wurde, eine weitere Parallele zur Replikationsstrategie der Hepadnaviren auf.
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Goto, Akira. "Co-evolution of simian foamy viruses (SFVs) with primates: comparative functional analyses of miRNAs expressed from SFVs." Kyoto University, 2020. http://hdl.handle.net/2433/253169.
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Regad, Tarik. "Rôle et devenir des corps nucléaires PML en réponse à l' interféron et lors des infections virales par le HFV et le virus de la rage." Paris 7, 2002. http://www.theses.fr/2002PA077221.
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Rua, Réjane. "Caractérisation génétique, moléculaire et immunologique de l'infection zoonotique par le virus Foamy in vitro et in vivo : étude de la transmission rétrovirale inter-espèces." Paris 7, 2013. http://www.theses.fr/2013PA077223.
Full textAbstract:
Le virus Foamy est un rétrovirus complexe ubiquitaire chez les primates non humains(PNH) cnez lesquels il établit une infection persistante sans apparente pathologie associée. Le virus Foamy se réplique activement dans la cavité buccale des PNH. Il est transmis à l'homme lors de morsures par les PNH. Il y établit une infection chronique à long-terme actuellement considérée comme non pathogène. Aucun cas de transmission secondaire d'Homme à Homme n'étant rapporté à ce jour, nous recherchons les facteurs à l'origine de l'apparente «restriction» du virus Foamy chez l'Homme. Les objectifs de ma thèse se déclinent en deux axes :1-Caractérisation génétique, moléculaire et cellulaire de l'infection par le virus Foamy chez l'Homme in vivo. Chez les individus infectés par le virus Foamy, nous montrons que la charge virale est faible et que l'ARN viral n'est pas détectable au niveau salivaire. Ceci pourrait contribuer à l'absence de dissémination virale inter-humaine. Nous montrons également que cette restriction des virus Foamy chez l'Homme ne peut pas s'expliquer par des modifications délétères majeures au niveau du génome viral. 2- Caractérisation de la réponse Interféron-I au virus Foamy in vitro. Nous montrons que le virus Foamy induit une forte réponse IFN-I au contact des PBMCs humaines, et que ce sont principalement les cellules dendritiques plasmacytoïdes (pDC) qui sont responsables de cette réponse. En utilisant une lignée de cellules dendritiques plasmacytoïdes, nous montrons que cette détection passe par le senseur endosomal TLR7 et qu'elle ne nécessite par l'infection productive des pDCFoamy viruses are complex retroviruses which are ubiquitous in non-human primates (NHP). They induce a persistent infection without apparent pathology. Foamy viruses actively repllcate in the oral cavity of NHP. They are transmitted to humans through NHP bites. Human infection is also lifelong and appàrently non pathogenic. As no case of secondary transmission has been reported to date, we searched for viral factors behind the apparent 'restriction" of Foamy viruses in humans. The objectives of my thesis are 1-Genetic, molecular and cellular characterization of human infection with foamy virus in vivo ln indlviduals infected with Foamy virus, we show that viral loads are low and viral RNA is not present ln the saliva. This couic' contribute to the absence of inter-human viral spread. We aise show that the restriction of Foamy virus in humans can not be explained by major deleterious changes in the viral genome. 2 - Characterization of type 1-interféron response to Foamy virus in vitro. We show that Foamy virus induces a strong type I-interferon response in contact with human PBMCs, and that the plasmacytoid dendritic tells (pDCs) are the major tell type responsible for this induction. Using a plasmacytoid dendritic tell sine, we show that viral strisILLI ucurstluellrandloesnotLecaroductive infection of 'DCs
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Aiewsakun, Pakorn. "Paleovirology : connecting recent and ancient viral evolution." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:370e0a28-ee67-441f-bce6-42ad4cdf9365.
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Endogenous viral elements, or viral genomic fossils, have proven extremely valuable in the study of the macroevolution of viruses, providing important, and otherwise unobtainable, insights into the ancient origin of viruses, and how their ancestors might have co-evolved with their hosts in the distant past. This type of investigation falls within the realm of paleovirologyâthe study of ancient viruses. Investigations of extant viruses and paleovirological analyses, however, often give conflicting results, especially those concerning viral evolutionary rates and timescales. Reconciling these two types of analyses is a necessary step towards a better understanding of the overall long-term evolutionary dynamics of viruses. The main study system of this thesis is foamy viruses (FVs). FVs are characterised by their stable co-speciation history with their hosts, allowing their evolutionary dynamics to be modelled and investigated over various timescales. This unique evolutionary feature makes FVs one of the best subjects for connecting recent and ancient viral evolution. The work here reports the discovery of several endogenous mammalian FVs, and examines how mammalian FVs co-evolve with their hosts. Analyses reveal a co-diversifying history of the two that could be dated back to the basal radiation of eutherians more than 100 million years ago. However, a small number of ancient FV cross-species transmissions could still be found, mostly involving New World monkey FVs. Based on this extended FV-mammal co-speciation pattern, this thesis investigates the long-term evolutionary rate dynamics of FVs, and shows that the rate estimates of FV evolution appear to decrease continuously as the rate measurement timescale increases, following a power-law decay function. The work presented here also shows that this so-called 'time-dependent rate phenomenon' is in fact a pervasive evolutionary feature of all viruses, and surprisingly, the rate estimates of evolution of all viruses seem to decay at the same speed, decreasing by approximately half for every 3-fold increase in the measurement timescale. Based on this power-law rate-decay pattern, we could infer evolutionary timescales of modern-day lentiviruses that are consistent with paleovirological analyses for the first time. Finally, this thesis reports the discovery of basal FV-like endogenous retroviruses (FLERVs) in amphibian and fish genomes. Phylogenetic analyses reveal that the progenitors of ray-finned fish FLERVs co-diversify broadly with their fish hosts, but also suggest that there might have been several ancient viral cross-class transmissions, involving lobe-finned fish, shark, and frog FLERVs. Again, by using the power-law rate-decay model, analyses in this thesis suggest that this major retroviral clade has an ancient Ordovician marine origin, originating together with their jawed vertebrate hosts more than 450 million years ago. This finding implies that the origin of retroviruses as a whole must be in the early Paleozoic Era, if not earlier. The results presented here bridge ancient and recent viral evolution.
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Stange, Annett. "Determinanten und Mechanismen der foamyviralen Partikelfreisetzung." Doctoral thesis, Technische Universität Dresden, 2007. https://tud.qucosa.de/id/qucosa%3A23849.
Full textAbstract:
Die Spumaretrovirinae, mit ihrer einzigen Gattung der Foamyviren (FV), nehmen aufgrund einer recht ungewöhnlichen Replikationsstrategie und Ähnlichkeiten mit den Hepadnaviren eine Sonderstellung innerhalb der Familie der Retroviren ein. Eine Besonderheit der FV ist, daß sie für die Partikelfreisetzung, im Gegensatz zu den Orthoretroviren, die beiden strukturellen Proteine Gag und Env benötigen. Das Gag- Protein trägt alle für den Kapsidzusammenbau nötigen strukturellen Komponenten, kann jedoch durch eine fehlende Membranbindungsdomäne nicht mit Zellmembranen assoziieren. Der Membrantransport der bereits im Zytoplasma zusammen gebauten FV Kapside wird vermutlich durch das FV Env-Protein vermittelt. Das FV Hüllprotein ist jedoch auch alleine zur Freisetzung von Kapsidlosen, Hüllprotein-haltigen subviralen Partikeln (SVP) fähig. Da eine Envunabhängige Freisetzung virus-ähnlicher Partikel durch ein FV Gag-Protein mit künstlichem Membrananker möglich ist, scheint das FV Gag-Protein auch essentielle strukturelle Elemente für die Partikelfreisetzung zu enthalten. In den letzten Jahren wurden große Fortschritte in der Erforschung der Freisetzung von membranumhüllten Viren und den daran beteiligten viralen Determinanten und zellulären Mechanismen gemacht. Wobei den meist in den viralen Kapsidproteinen vorkommenden Late (L)-Domänen und deren Interaktion mit dem zellulären Proteinsortierungsweg in Multivesikuläre Körperchen (MVB) eine besondere Bedeutung zu kommt. Über die FV virale und subvirale Partikelfreisetzung und die dabei involvierten strukturellen viralen Domänen und zellulären Proteinen war jedoch bisher wenig bekannt. Im Rahmen dieser Arbeit konnte durch Mutationsanalysen von drei potentiellen L-Domän Sequenzmotiven im Prototyp FV (PFV) Gag-Protein ein, innerhalb der Primaten FV konserviertes, PSAP Konsensusmotiv als funktionelle L-Domäne charakterisiert werden. Dessen Mutation führte zu klassischen L-Domän Defekten mit verringerter Partikelfreisetzung, sowie einer elektronenmikroskopisch sichtbaren Arretierung der Virusknospung und seine Funktion war durch homo- und heterologe L-Domän Motive anderer Retroviren teilweise oder vollständig ersetzbar. Ein PPPI Motiv in PFV Gag, mit Ähnlichkeit zur L-Domän PPXY Konsensussequenz, schien jedoch keinen Einfluß auf die FV Freisetzung zu besitzen. Die Charakterisierung eines in allen FV Gag-Proteinen konservierten YXXL Motivs ließ eher auf eine wichtige Rolle beim korrekten Kapsidzusammenbau, als auf eine klassische LDomän Funktion schließen. Eine korrekte Kapsidmorphogenese schien entscheidend für die reverse Transkription des Virusgenoms zu sein. Durch Koexpression verschiedener dominant-negativer Mutanten des zellulären ESCRT-Proteinssortierungsweges konnte gezeigt werden, daß die virale Partikelfreisetzung von PFV augenscheinlich dem generellen Model der Freisetzung vieler membranumhüllter Viren über das VPS-System folgt. Eine spezifische Interaktion des PFV Gag PSAP L-Domän Motivs mit TSG101, einer frühen Komponente der ESCRT-Komplexe, verbindet PFV mit dem VPS-Sortierungsweg der Zelle. Die besondere Fähigkeit des FV Env-Proteins zur Freisetzung von SVPs wurde bereits vor einiger Zeit entdeckt, dennoch war bisher nichts über die viralen und zellulären Determinanten bekannt, die zu einer Knospung des Env-Proteins in Vesikel führten. Durch eine Reihe von Deletions- und Mutationsanalysen des PFV Env-Proteins konnten in dieser Arbeit zwei für die SVP-Freisetzung inhibitorische Abschnitte am N- und C-Terminus der zytoplasmatischen Domänen des Env- Proteins ermittelt werden. Weiterhin wurden essentielle Sequenzen im Leaderpeptid, sowie die Notwendigkeit der Membranspannenden Domäne der Transmembran- Untereinheit für die SVP-Freisetzung festgestellt. Obwohl das PFV Env-Protein kein bekanntes L-Domän Sequenzmotiv enthält, konnte ein Einfluß später Komponenten der ESCRT-Maschinerie auf die SVP-Bildung beobachtet werden. Wobei die genaue Eintrittsstelle in den VPS-Weg im Rahmen dieser Arbeit nicht definiert werden konnte. Die vorgenommen Analysen lassen vermuten, daß die Bildung von SVPs durch die Konzentration der Env-Proteine in der Zellmembranen reguliert wird. Welche genauen Mechanismen dabei zu Grunde liegen und wieweit die zelluläre Ubiquitinylierungsmaschinerie involviert ist, bedarf jedoch weiterer Erforschung. Die Ergebnisse dieser Arbeit verdeutlichen erneut die Sonderstellung der FV innerhalb der Familie der Retroviren. Auf der einen Seite folgt die foamyvirale Viruspartikelfreisetzung den typischen Mechanismen der retroviralen Virusknospung. Andererseits zeigt die Freisetzung von subviralen Partikeln, die bei keinem anderen Retrovirus bisher beobachtet wurde, eine weitere Parallele zur Replikationsstrategie der Hepadnaviren auf.
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Betsem, a. Betsem Edouard. "Aspects épidémiologiques et variabilité génétique moléculaire des virus FOAMY et HHV-8 dans des populations rurales du Sud Cameroun : des premières étapes de l'émergence virale à la persistance et transmission interhumaine." Paris 7, 2011. http://www.theses.fr/2011PA077155.
Full textAbstract:
Ce travail, décrit les aspects épidémiologiques de l'émergence par transmission inter-espèce des virus foamy simiens dans des régions du Sud Cameroun, de même que les aspects d'épidémiologie sérologique et moléculaire de l'HHV-8. Les virus foamy appartiennent appartiennent au genre Spumavirus dans la famille Retroviridae et infectent naturellement de nombreuses espèces de primates non-humains. Des cas humains d'infection par transmission interespèces ont été démontrés dans des situations professionnelles en Amérique du Nord et en Europe, et en milieu naturel en Asie et en Afrique. La transmission secondaire et la pathogénicité de ces virus restent non démontrés. Autour de la réserve du Dja, les populations les populations sont fréquemment en contact avec différentes espèces de PNH. Un «groupe contact» de 198 individus âgés à 80% de 15 à 40 ans a été testé et la séroprévalence de l'infection y est de 26,7% (53/198). De l'ADN viral a été amplifié chez 20,7% des individus (41/198) avec une durée moyenne de persistance virale de 17 ans. Dans la population générale, la séroprévalence chez 1321 (5 - 90 ans) personnes testées est de 2% (26/1321) et de l'ADN viral est retrouvé dans 0,2% (2/1321) des cas. Les morsures et les grands singes sont fortement associés à l'infection mais d'autres modes de transmission peuvent être évoqués. Les charges (pro)virales sont faibles (>1 - 145 copies/10⁵ copies), la transmission secondaire n'a pas pu être mise en évidence parmi 30 épouses et 12 enfants apparentés à des cas index. L'analyse de 38 séquences de 425 pb de gorille (30), de chimpanzé (3) et de cercopithèque (5) a montré une faible variabilité entre ces dernières. Une étude cas-témoins recherchant la pathogénicité du virus foamy chez les cas index est en cours. L'HHV-8 est un gammaherpès virus du genre Rhadinovirus. Il est responsable de toutes les formes du sarcome de Kaposi dont la forme endémique est très fréquente au Cameroun. Peu de données existent sur l'HHV-8 au Cameroun. Une population de 2063 individus (787 Pygmées de 2 à 83 ans et 1276 Bantous de 2 à 85 ans) testée révèle une séroprévalence HHV-8 de 37,2% (768/2063) plus élevée chez les Pygmées (x² =50. 08, p<10⁻⁶ ) sans différence entre les sexes. Les 29 séquences obtenues appartiennent aux sous-types circulant en Afrique A5 et B. Des études complémentaires incluant des patients avec un SK sont en coursThe present work describes epidemiological features of cross-species emergence of simian foamy viruses in remote human populations in South Cameroon, as well as serological and molecular epidemiology of human herpes virus 8. FV belong to the Spumavirus genera among the Retroviridae. Human cross-species infections from NHP have been demonstrated in occupational situations in North America and Europe, and in natural settings in Asia and Central Africa. Secondary transmission and pathogenicity in infected persons is still an open issue. Populations neighbouring the Dja nature reserve are frequently in contact with different species of NHP. We tested 198 individuals in a "contact group" (80 % aged 15 to 40 years), who reported a physical contact with a NHP, mostly during hunting (83% of these occurred during the last 20 years). SFV seroprevalence among these is 26. 7% (53/198). Viral DNA from the po/-ln and/or LTR were amplified in 20. 7% (41/198) of these individuals with an average persistence period of 17 years. In a group identified as "general population", we tested 1321 persons aged 5 to 90 years. SFV seroprevalence in this group is 2% (26/1321) and viral DNA was amplified in 0. 2% (2/1321). Factors associated to this infection are apes and bites, but other transmission modes can be considered. (Pro)viral loads are low (<1 to 145 copies / 10⁵ cells). Secondary transmission from an index case to a family member could not be demonstrated in 30 wives of 12 children despite a positive serology was found in a spouse. Analysis of 38 (425 bp) po/-ln sequences shows low variability. They belong to gorilla (30), chimpanzee (3) and Cercopithecus (5) species found in the areas, matching the hunters story. A case control study is underway in order to search for pathogenicity in infected individuals. HHV-8 belongs to the Gammaherpesvirinae subfamily and to the Rhadinovirus genera. This virus is responsible of all forms of Kaposi sarcoma, endemic in Cameroon. Data on the infection and the virus are very rare. A population of 1263 (787 Pygmies aged 2 to 83 years and 1276 Bantus aged 2 to 85 years) individuals was tested for HHV-8 and a high 37. 2% (768/2063) seroprevalence rate was found. Bantus are more infected than Pygmies (x² =50. 08, p<10⁻⁶ ) and no differences was observed according to sex. The 29 polymorphic 737 bp Kl (ORF_K1) sequences obtained belong to circulating A5 and B sequences found in Africa. Complementary analyses are underway including KS patients
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Mouinga, Ondeme Augustin Ghislain. "Infection naturelle des primates non humains par les spumavirus et transmission inter-espèces au Gabon." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20706/document.
Full textAbstract:
Les spumavirus (SV) sont des rétrovirus exogènes de la sous-famille des Spumavirinae appartenant à la famille des Retroviridae. L’infection naturelle chez les primates non humains (PNH) est décrite dans la nature et en captivité, avec 75 à 100% de singes adultes infectés. Chez les PNH, la transmission des SV se fait à travers des morsures très graves. Par ailleurs, ces virus ont été isolés chez des travailleurs de zoo, exposés aux animaux infectés dans le cadre de leur travail. Récemment, des études ont aussi montré l’infection dans le milieu naturel chez des chasseurs au Cameroun. Cependant, aucune pathologie n’a jamais pu être associée à l’infection par ces virus. Au Gabon, les infections par des SV n’ont été que très peu étudiées. Les objectifs de cette thèse sont donc :1) D’évaluer au Gabon, la prévalence des SV dans la colonie de Mandrills en captivité au centre de primatologie (CDP) du CIRMF, ainsi que dans la nature chez un grand nombre d’espèces de primates non humains ;2) De caractériser sur le plan moléculaire les souches SV circulant au Gabon ;3) D’identifier chez des personnes mordues par un PNH des cas de transmission interespèces.Dans la première partie de ce travail, nous avons montré que 83% (70/84) des mandrills du CDP (38 males et 46 femelles) et 60% (9/15) des mandrills sauvages étaient infectés par le SV. L’infection augmentait avec l’âge et la différence entre les males et les femelles n’était pas significative (84% et 82%, respectivement). Un fragment de 425pb de l’integrase a été amplifié dans 60/69 et 53 nouvelles séquences ont été isolées. L’analyse phylogénétique a mis en évidence la circulation de 11 souches différentes dans la colonie, toutes étroitement liées sauf une. La confirmation de ces résultats à l’aide de séquences de virus chez des mandrills sauvages démontre l’existence de deux groupes de mandrills (nord et sud) localisés de part et d’autre du fleuve Ogooué. En plus, nous avons étudié 497 échantillons de plasma et tissus prélevés chez 13 espèces simiennes dans la nature. L’analyse sérologique a montré l’infection par SV chez 10.8% (31/286). Le fragment de l’integrase a été caractérisé dans 38/497 échantillons, avec la description de nouvelles infections naturelles chez les C. solatus, C. nictitans et C. cephus. Dans la deuxième partie, nous avons décrit l’infection chez 20% (4/20) des travailleurs du CDP. La caractérisation moléculaire a été faite chez deux d’entre eux: l’un a été mordu il y a 10 ans par un mandrill clairement identifié, et l’autre par un macaque 25 ans auparavant. En milieu naturel, nous avons testé 78 personnes mordues par un PNH. Au total, 19 personnes mordues (24%) étaient séropositives pour le SV. Sur ces 19 individus, 15 séquences virales ont été obtenues dont 12 de gorilles, 2 de chimpanzés et une de cercopithèque. Ces résultats montrent que les PNH du Gabon sont infectés par les SV et que la transmission inter espèces des SV intervient chez des personnes mordues par ces animauxFoamy viruses are members of the Spumavirus genus of the Retroviridae family. These complex exogenous retroviruses are highly prevalent in several animal species, including nonhuman primates (NHP). The seroprevalence of antibodies to Simian foamy virus (SFVs) in captive adult NHP populations can reach 75-100%. SFV infection has been reported in people occupationally exposed to nonhuman primates in zoos. Recently, naturally acquired SFV infections were described in a group of hunters living in Cameroon, central Africa.In Gabon, foamy viruses are less studied. In our study, we evaluated the natural history of SFV in a free-ranging colony of mandrills (CIRMF primate center) and in mandrills living in natura in Gabon (central Africa). We also determined the SFV prevalence in a series of 497 NHP living in different parts of Gabon. Lastly, we investigated the possible transmission of SFVs to humans.First, SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills.Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. Among the NHP, 10.8% (31/286) of the plasma/sera were SFV seropositive. Integrase gene was characterized in 38 samples with novel SFVs in several species of Cercopithecus.Second, the presence of SFV was also evaluated in 20 people who worked closely with mandrills and other NHP. Integrase region of 425 bp was found in 2/20 (10%) humans. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV-infected, both at the Primate Centre. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. The second man had a sequence close to SFVmac sequences. Of the 78 people, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high interspecies transmission of SFVs from gorilla bites
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Nistal, Markus. "Etablierung eines proviralen molekularen Klons des Equine Foamy Virus (EFV)." Doctoral thesis, 2010. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-48928.
Full textAbstract:
Foamyviren (FV) sind komplexe Retroviren, die sich in ihrem Replikationszyklus in vielerlei Hinsicht von den klassischen Retroviren (Orthoretrovirinae) unterscheiden. Funktional nehmen sie eine Mittelstellung zwischen Orthoretroviren und Hepadnaviren ein. Wichtige Unterschiede zu Orthoretroviren liegen in der Reifung und Ausschleusung viraler Partikel. Die Partikelreifung findet wie bei Typ B/D-Orthoretroviren an intrazytoplasmatischen Strukturen statt. Die Partikelfreisetzung wurde bei FV im Gegensatz zu Orthoretroviren hauptsächlich als Ausknospen an intrazellulären Membranen beschrieben. Neben anderen für das Ausknospen relevanten Motiven wurde im viralen Glykoprotein ein ER-Rückführungsmotiv gefunden, das in fast allen FV vorhanden ist und die Ausschleusung an intrazytoplasmatische Membranen dirigieren soll. Im Jahr 2000 wurde erstmals ein FV aus Pferden isoliert. Dieses Equine Foamy Virus (EFV) zeigte die beschriebenen Eigenschaften anderer FV, jedoch ein ausschließliches Ausknospen viraler Partikel an der Plasmamembran. Ein ER-Rückführungsmotiv ist im Genom von EFV nicht konserviert. In dieser Arbeit wurde aus mit EFV infizierten Zellkulturen mit Hilfe der PCR das virale Genom amplifiziert und kloniert. Die Genomanteile wurden zu einem proviralen molekularen Klon des Virus zusammengefügt. Eine vollständige Sequenzierung erlaubte die Identifikation expressionskritischer Veränderungen. Mittels weiterer Klonierungen und PCR-Mutagenese konnten eine Sequenzunterbrechung und verschiedene Stopp-Mutationen korrigiert werden. Verschiedene Zelllinien wurden mit dem proviralen Klon transfiziert, eine quantitativ relevante Anzucht von Viren in der Zellkultur gelang trotz Nachweis von viralem Genom durch PCR nach mehreren zellfreien Passagen nicht. Als Ursache der fehlenden Virusexpression sind Mutationen des Matrizengenoms vor der Klonierung zu vermuten, die für die effektive Replikation relevante, aber bisher noch nicht bekannte Positionen in regulatorischen Proteinen oder LTR-Regionen betreffenFoamy viruses are complex retroviruses, which differ from classic retroviruses in many aspects of their replication cycle. Their characteristics are between orthoretroviruses and hepadnaviruses. Important differences to orthoretroviruses concern particle maturation and budding. Particle maturation takes place at intracytoplasmatic structures like with type B/D retroviruses. Particle release in foamy viruses was described as budding from intracellular membranes in opposite to orthoretroviruses budding from plasma membrane. Besides other relevant budding motives an ER retrieval motif was found in almost all foamy viral glykoproteins which is supposed to direct particle budding to intracytoplasmatic membranes. In 2000 a foamy virus was isolated from horses. This equine foamy virus (EFV) showed the usual foamy viral characteristics, but an exclusive budding of viral particles from plasma membrane. An ER retrieval motif is mot conserved among EFV. For this study the viral genome was amplified from EFV-infected cell cultures by PCR and cloned. The genome parts were put together to a proviral molecular clone of EFV. Complete sequencing allowed identification of critical changes in comparison to the published sequence. A disruption of the sequence and several stop mutations could be corrected by subsequent cloning and PCR mutagenesis. Several adherent cell lines were transfected with the proviral clone, a quantitatively relevant culture of the virus was not achieved despite proof of viral genome by PCR after several cell-free passages. As a cause for the lack of expression has to be thought of mutations of the template genome before cloning. Those mutations may affect yet unknown positions in regulatory proteins or LTR regions relevant for effective replication