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Littérature scientifique sur le sujet « Flaviviru »

Auteur : Grafiati

Publié le 1 avril 2023

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Articles de revues sur le sujet "Flaviviru"

Morita, Eiji, et Youichi Suzuki. « Membrane-Associated Flavivirus Replication Complex—Its Organization and Regulation ». Viruses 13, n^o 6 (3 juin 2021) : 1060. http://dx.doi.org/10.3390/v13061060.

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Flavivirus consists of a large number of arthropod-borne viruses, many of which cause life-threatening diseases in humans. A characteristic feature of flavivirus infection is to induce the rearrangement of intracellular membrane structure in the cytoplasm. This unique membranous structure called replication organelle is considered as a microenvironment that provides factors required for the activity of the flaviviral replication complex. The replication organelle serves as a place to coordinate viral RNA amplification, protein translation, and virion assembly and also to protect the viral replication complex from the cellular immune defense system. In this review, we summarize the current understanding of how the formation and function of membrane-associated flaviviral replication organelle are regulated by cellular factors.

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Fontoura, Marina Alves, Rebeca Fróes Rocha et Rafael Elias Marques. « Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection ». Life 11, n^o 7 (20 juillet 2021) : 717. http://dx.doi.org/10.3390/life11070717.

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Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.

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Wee, Sheena, Asfa Alli-Shaik, Relus Kek, Hannah L. F. Swa, Wei-Ping Tien, Vanessa W. Lim, Yee-Sin Leo, Lee-Ching Ng, Hapuarachchige C. Hapuarachchi et Jayantha Gunaratne. « Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis ». Proceedings of the National Academy of Sciences 116, n^o 14 (18 mars 2019) : 6754–59. http://dx.doi.org/10.1073/pnas.1817867116.

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Targeted proteomic mass spectrometry is emerging as a salient clinical diagnostic tool to track protein biomarkers. However, its strong analytical properties have not been exploited in the diagnosis and typing of flaviviruses. Here, we report the development of a sensitive and specific single-shot robust assay for flavivirus typing and diagnosis using targeted mass spectrometry technology. Our flavivirus parallel reaction monitoring assay (fvPRM) has the ability to track secreted flaviviral nonstructural protein 1 (NS1) over a broad diagnostic and typing window with high sensitivity, specificity, extendibility, and multiplexing capability. These features, pivotal and pertinent to efficient response toward flavivirus outbreaks, including newly emerging flavivirus strains, circumvent the limitations of current diagnostic assays.fvPRM thus carries high potential in positioning itself as a forerunner in delivering early and accurate diagnosis for disease management.

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van den Elsen, Kaïn, Jun Ping Quek et Dahai Luo. « Molecular Insights into the Flavivirus Replication Complex ». Viruses 13, n^o 6 (21 mai 2021) : 956. http://dx.doi.org/10.3390/v13060956.

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Flaviviruses are vector-borne RNA viruses, many of which are clinically relevant human viral pathogens, such as dengue, Zika, Japanese encephalitis, West Nile and yellow fever viruses. Millions of people are infected with these viruses around the world each year. Vaccines are only available for some members of this large virus family, and there are no effective antiviral drugs to treat flavivirus infections. The unmet need for vaccines and therapies against these flaviviral infections drives research towards a better understanding of the epidemiology, biology and immunology of flaviviruses. In this review, we discuss the basic biology of the flavivirus replication process and focus on the molecular aspects of viral genome replication. Within the virus-induced intracellular membranous compartments, flaviviral RNA genome replication takes place, starting from viral poly protein expression and processing to the assembly of the virus RNA replication complex, followed by the delivery of the progeny viral RNA to the viral particle assembly sites. We attempt to update the latest understanding of the key molecular events during this process and highlight knowledge gaps for future studies.

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Thibodeaux, Brett A., et John T. Roehrig. « Development of a Human-Murine Chimeric Immunoglobulin M Antibody for Use in the Serological Detection of Human Flavivirus Antibodies ». Clinical and Vaccine Immunology 16, n^o 5 (18 mars 2009) : 679–85. http://dx.doi.org/10.1128/cvi.00354-08.

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ABSTRACT Current diagnosis of human flaviviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Broad application of this assay is hindered by a lack of standardized human positive-control sera that react with the wide variety of flaviviruses that can cause human disease, e.g., dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), and St. Louis encephalitis virus (SLEV). We have created a human-murine chimeric antibody combining the variable regions of the broadly flavivirus cross-reactive murine monoclonal antibody (MAb) 6B6C-1 and the constant region of human IgM to produce a standardized reagent capable of replacing human positive-control sera in a MAC-ELISA for the diagnosis of all human flaviviral infections. The human-murine chimeric IgM antibody secreted from plasmid-transformed Sp2/0-Ag14 cells had a level of serological activity identical to that of 6B6C-1 as measured by ELISA, immunoblotting, and MAC-ELISA for multiple members of the flavivirus genus, including WNV, SLEV, YFV, DENV, and JEV.

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Seo, Min-Goo, Hak Seon Lee, Sung-Chan Yang, Byung-Eon Noh, Tae-Kyu Kim, Wook-Gyo Lee et Hee Il Lee. « National Monitoring of Mosquito Populations and Molecular Analysis of Flavivirus in the Republic of Korea in 2020 ». Microorganisms 9, n^o 10 (2 octobre 2021) : 2085. http://dx.doi.org/10.3390/microorganisms9102085.

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The Korea Disease Control and Prevention Agency has established centers at 16 locations to screen vector populations and pathogens. The aims of this study were to determine the relative spatiotemporal distributions of mosquitoes that are flavivirus vectors, and to correlate them with instances of flaviviral disease in the Republic of Korea (ROK). We collected 67,203 mosquitoes in traps at 36 collection sites in 30 urban regions and migratory bird habitats in 2020. The trap index was 36.6, and the predominant mosquito species were the Culex pipiens complex, Armigeres subalbatus, Aedes albopictus, Aedes vexans, and Culex tritaeniorhynchus. The mosquitoes were pooled into 4953 pools to monitor flavivirus infection. We determined that the minimum infection rate of flavivirus was 0.01%. Japanese encephalitis virus (JEV) was detected in only seven pools of Culex orientalis from Sangju, and we isolated JVE from two pools. All detected JEV was found to be genotype V by phylogenetic analysis. To the best of our knowledge, this is the first study to isolate genotype V JVE from Culex orientalis in the ROK. Subsequent geographical and ecological studies on mosquitoes will help improve our understanding of the relative risk of flavivirus infection. Future studies should analyze mosquito species distribution and improve flavivirus monitoring and long-term surveillance.

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Qiu, Yang, Yan-Peng Xu, Miao Wang, Meng Miao, Hui Zhou, Jiuyue Xu, Jing Kong et al. « Flavivirus induces and antagonizes antiviral RNA interference in both mammals and mosquitoes ». Science Advances 6, n^o 6 (février 2020) : eaax7989. http://dx.doi.org/10.1126/sciadv.aax7989.

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Mosquito-borne flaviviruses infect both mammals and mosquitoes. RNA interference (RNAi) has been demonstrated as an anti-flavivirus mechanism in mosquitoes; however, whether and how flaviviruses induce and antagonize RNAi-mediated antiviral immunity in mammals remains unknown. We show that the nonstructural protein NS2A of dengue virus-2 (DENV2) act as a viral suppressor of RNAi (VSR). When NS2A-mediated RNAi suppression was disabled, the resulting mutant DENV2 induced Dicer-dependent production of abundant DENV2-derived siRNAs in differentiated mammalian cells. VSR-disabled DENV2 showed severe replication defects in mosquito and mammalian cells and in mice that were rescued by RNAi deficiency. Moreover, NS2As of multiple flaviviruses act as VSRs in vitro and during viral infection in both organisms. Overall, our findings demonstrate that antiviral RNAi can be induced by flavivirus, while flavivirus uses NS2A as a bona fide VSR to evade RNAi in mammals and mosquitoes, highlighting the importance of RNAi in flaviviral vector-host life cycles.

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Wu, Bingan, Zhongtian Qi et Xijing Qian. « Recent Advancements in Mosquito-Borne Flavivirus Vaccine Development ». Viruses 15, n^o 4 (23 mars 2023) : 813. http://dx.doi.org/10.3390/v15040813.

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Lately, the global incidence of flavivirus infection has been increasing dramatically and presents formidable challenges for public health systems around the world. Most clinically significant flaviviruses are mosquito-borne, such as the four serotypes of dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus and yellow fever virus. Until now, no effective antiflaviviral drugs are available to fight flaviviral infection; thus, a highly immunogenic vaccine would be the most effective weapon to control the diseases. In recent years, flavivirus vaccine research has made major breakthroughs with several vaccine candidates showing encouraging results in preclinical and clinical trials. This review summarizes the current advancement, safety, efficacy, advantages and disadvantages of vaccines against mosquito-borne flaviviruses posing significant threats to human health.

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Bidet, Katell, et Mariano A. Garcia-Blanco. « Flaviviral RNAs : weapons and targets in the war between virus and host ». Biochemical Journal 462, n^o 2 (7 août 2014) : 215–30. http://dx.doi.org/10.1042/bj20140456.

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Flaviviruses are a genus of (+)ssRNA (positive ssRNA) enveloped viruses that replicate in the cytoplasm of cells of diverse species from arthropods to mammals. Many are important human pathogens such as DENV-1–4 (dengue virus types 1–4), WNV (West Nile virus), YFV (yellow fever virus), JEV (Japanese encephalitis virus) and TBEV (tick-borne encephalitis). Given their RNA genomes it is not surprising that flaviviral life cycles revolve around critical RNA transactions. It is these we highlight in the present article. First, we summarize the mechanisms governing flaviviral replication and the central role of conserved RNA elements and viral protein–RNA interactions in RNA synthesis, translation and packaging. Secondly, we focus on how host RNA-binding proteins both benefit and inhibit flaviviral replication at different stages of their life cycle in mammalian hosts. Thirdly, we cover recent studies on viral non-coding RNAs produced in flavivirus-infected cells and how these RNAs affect various aspects of cellular RNA metabolism. Together, the article puts into perspective the central role of flaviviral RNAs in modulating both viral and cellular functions.

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Blahove, Maria Raisa, et James Richard Carter. « Flavivirus Persistence in Wildlife Populations ». Viruses 13, n^o 10 (18 octobre 2021) : 2099. http://dx.doi.org/10.3390/v13102099.

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A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also infect wildlife at a considerable rate, persistently cycling between ticks/mosquitoes and small mammals and reptiles and non-human primates and humans. Substantially increasing evidence of viral persistence in wildlife continues to be reported. In addition to in humans, viral persistence has been shown to establish in mammalian, reptile, arachnid, and mosquito systems, as well as insect cell lines. Although a considerable amount of research has centered on the potential roles of defective virus particles, autophagy and/or apoptosis-induced evasion of the immune response, and the precise mechanism of these features in flavivirus persistence have yet to be elucidated. In this review, we present findings that aid in understanding how vector-borne flavivirus persistence is established in wildlife. Research studies to be discussed include determining the critical roles universal flavivirus non-structural proteins played in flaviviral persistence, the advancement of animal models of viral persistence, and studying host factors that allow vector-borne flavivirus replication without destructive effects on infected cells. These findings underscore the viral–host relationships in wildlife animals and could be used to elucidate the underlying mechanisms responsible for the establishment of viral persistence in these animals.

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Thèses sur le sujet "Flaviviru"

Lequime, Sébastian. « Interactions flavivirus-moustiques : diversité et transmission ». Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066081/document.

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Les flavivirus sont des virus à ARN parmi lesquels certains sont des arbovirus transmis entre hôtes vertébrés par des vecteurs arthropodes, notamment des moustiques. L'interaction avec les moustiques est centrale dans la biologie des flavivirus par son influence sur leur diversité génétique et transmission, mais certains de ses aspects restent méconnus. Au cœur de cette thèse, des approches basées sur les « big data », générées par des technologies modernes ou par compilation de travaux plus anciens, ont éclairé d’un jour nouveau la complexité des relations moustique-flavivirus. En explorant des génomes de moustiques anophèles, nous avons identifié et caractérisé des éléments viraux endogènes d'origine flavivirale chez Anopheles sinensis et An. minimus, suggérant l'existence de flavivirus infectant les anophèles et révélant une facette insoupçonnée de leur diversité. Par ailleurs, nous avons exploré, par séquençage haut-débit, la fine interaction entre le génotype du moustique Aedes aegypti et la diversité intra-hôte du virus de la dengue-1. Nos résultats montrent un fort effet de la dérive génétique lors de l'infection initiale, diminuant l'importance relative de la sélection naturelle, et une modulation de la diversité génétique intra-hôte du virus par le génotype du moustique. Enfin, nous avons compilé la littérature sur la transmission verticale des arbovirus chez les moustiques, c'est-à-dire de la femelle infectée à sa descendance, afin d'identifier des facteurs techniques et biologiques sous-jacents. Nos résultats améliorent la compréhension de ce mode de transmission et des stratégies employées par les arbovirus pour persister dans l’environnement
Flaviviruses are RNA virus among which some are arboviruses transmitted between vertebrate hosts and arthropod vectors, like mosquitoes. The interaction with mosquitoes is key in the biology of flaviviruses because it influences their genetic diversity and transmission. However, some aspects however are still poorly understood. At the heart of the work presented in this dissertation, strategies based on ‘big data’, both by taking advantage of modern technologies and by compiling older literature, highlighted new aspects of the complex relationships between flaviviruses and mosquitoes. While exploring Anopheles mosquito genomes, we identified and characterized endogenous viral elements of flaviviral origin in Anopheles sinensis and An. minimus, which supports the existence of flaviviruses infecting Anopheles mosquitoes and highlights new aspected of their diversity. Besides, we explored, by deep sequencing, the fine-tuned interaction between genotypes of the mosquito Aedes aegypti and the intra-host diversity of dengue virus 1. Our results showed a strong effect of genetic drift during initial infection, reducing the relative importance of natural selection, and a modulation of the intra-host viral genetic diversity by the mosquito genotype. Finally, we assembled the litterature on arbovirus vertical transmission in the mosquito vector, i.e. from an infected female to her offspring, in order to identify underlying technical and biological predictors. Our results increase our understanding of this transmission mode and the strategies employed by arboviruses to persist in their environment

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Khou, Cécile. « Etude du neurotropisme des Flavivirus neuropathogènes ». Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC305/document.

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Les Flavivirus neuropathogènes, tels que le virus de l’encéphalite japonaise (JEV), le virus West Nile (WNV), le virus de la fièvre jaune (YFV) et le virus Zika (ZIKV) causent des maladies neurologiques. Ces maladies sont dues à une infection des cellules du système nerveux central (CNS) par ces virus. Le CNS est un organe privilégié, isolé des agents pathogènes par une barrière entre le sang et le cerveau, appelée barrière hémato-encéphalique (BBB). Les Flavivirus neuropathogènes capables de traverser cette BBB afin d’atteindre leurs cellules cibles, localisées dans le CNS, sont neuroinvasifs. Le but de cette étude est de comprendre les mécanismes cellulaires permettant aux Flavivirus de traverser la BBB et les effets de l’infection par les virus ZIKV et WNV des cellules du CNS sur le développement de celles-ci.Le YFV est un virus hépatotrope, infectant majoritairement le foie et les reins. Deux vaccins vivants atténués dirigés contre le YFV, le vaccin FNV (pour French Neurotropic Virus) et le vaccin 17D, ont été obtenus empiriquement par passages successifs de souches virulentes de YFV sur cerveaux de souriceaux. Ces vaccins ne causent plus de maladies touchant les reins et le foie, mais peuvent parfois causer des encéphalites post-vaccinales. Ces cas d’encéphalites démontrent que ces souches vaccinales sont devenues neurovirulentes mais aussi neuroinvasives car les virus ont pu franchir la BBB. A cause d’une incidence trop élevée d’encéphalites post-vaccinales par rapport au vaccin 17D, le vaccin FNV a été retiré du marché dans les années 1980.Le JEV est un virus neurotrope, causant des encéphalites graves en Asie du Sud-Est. A ce jour, il existe un vaccin vivant atténué, le JEV SA14-14-2, obtenu empiriquement par passages successifs d’une souche virulente sur cellules de hamster. Ce vaccin est moins neurovirulent et moins neuroinvasif que les souches virulentes de JEV en modèle de souris, et protège contre des infections humaines par le JEV. Cependant, des cas d’encéphalites ont été rapportés après injection de ce vaccin. Il apparait donc que, dans certains cas, la souche vaccinale JEV SA14-14-2 est capable de traverser la BBB et d’infecter les cellules neuronales. Les dernières épidémies à virus ZIKV en Polynésie Française et en Amérique du Sud ont induit une augmentation de cas de malformations congénitales dans les zones touchées. Cela a soulevé de nouvelles questions quant à la capacité d’un Flavivirus à provoquer des malformations congénitales du CNS. Dans cette étude, nous avons identifié les mécanismes cellulaires permettant aux Flavivirus de traverser la BBB et les effets de l’infection par les virus ZIKV et WNV des cellules du CNS sur le développement de celles-ci.Nous avons utilisé deux systèmes in vitro permettant d’étudier le développement du CNS et la neuroinvasion des Flavivirus. Un premier système consiste en l’infection de coupes de cerveaux d’embryon de souris. En utilisant ce système, nous avons montré que le ZIKV a un tropisme préférentiel pour les cellules progénitrices de neurones, alors que le WNV a un tropisme préférentiel pour les neurones. Nous avons également montré que l’infection des progéniteurs neuronaux par le ZIKV induit un arrêt de la mitose cellulaire, alors que l’infection par le WNV n’a aucun effet sur la mitose. L’étude sur l’effet apoptotique de l’infection par les deux virus WNV et ZIKV n’a montré aucune différence entre les deux virus à des temps précoces d’infection.Un deuxième système a été mis au point pour l’étude de la neuroinvasion par les Flavivirus neuropathogènes. Ce système est composé de cellules endothéliales hCMEC/D3 pouvant former des jonctions serrées. Ces cellules ont été cultivées sur filtres d’insert de puits de culture cellulaire Transwell, placés au-dessus de cellules neuronales humaines. A l’aide de ce système, nous avons comparé la capacité à traverser la BBB de plusieurs Flavivirus
Neuropathogenic Flaviviruses, such as Japanese encephalitis virus (JEV), West Nile virus (WNV), yellow fever virus (YFV) and Zika virus (ZIKV), cause neurological diseases. These diseases are due to viral infection of central nervous system (CNS) cells. The CNS is a privileged organ, isolated from pathogenic agents by a barrier between the blood and the barrier, called the blood-brain barrier (BBB). Neuropathogenic Flaviviruses which can cross this BBB in order to reach their target cells in the CNS, are neuroinvasive. This study aims at understanding the cellular mechanisms by which YFV and JEV Flaviviruses cross the BBB and the effects of viral infection by WNV and ZIKV of the CNS cells during neocortex development.YFV is a hepatrotopic virus, which mostly infects the liver and the kidneys. The two live-attenuated vaccines against YFV, the FNV (for French Neurotropic Virus) vaccine and the 17D vaccine, were obtained empirically by several passages in suckling mouse brain of YFV virulent strains. These vaccines do not cause any disease targeting the liver or the kidneys, but can sometimes cause post-vaccine encephalitis. These encephalitis cases suggest that the vaccine strains have become neurovirulent and neuroinvasive. Due to high risks of post-vaccine encephalitis, the FNV vaccine use was discontinued in the 1980s.JEV is a neurotropic virus, causing acute encephalitis in South East Asia. To date, there is a live-attenuated vaccine against JEV, the JEV SA14-14-2 vaccine, which was obtained empirically by several passages in primary hamster kidney cells. This vaccine is less neurovirulent and less neuroinvasive than JEV virulent strains in mouse model, and it protects against JEV infections. However, some cases of post-vaccine encephalitis were reported. It thus seems that, in some cases, the vaccine strain JEV SA14-14-2 is able to cross the BBB and infect neuronal cells.The recent ZIKV epidemics in French Polynesia and South America were linked to an increase in the number of congenital malformations, rising questions regarding the capacity of a Flavivirus to induce CNS congenital malformations.In this study, we have identified cellular mechanisms involved in Flavivirus neuroinvasion and studied the effect of ZIKV and WNV infection of neuronal cells under development.To study CNS development, we have infected mouse embryos brain slices. We were able to show that ZIKV has a preferential tropism for neuronal progenitors, whereas WNV has a preferential tropism for neuronal cells. We also show that infection of neuronal progenitors by ZIKV impairs the cell life cycle, whereas no effect on the cell life cycle was observed for WNV-infected cells. Studies on apoptosis induction did not show any difference between both viruses at early time points of infection.To study Flavivirus neuroinvasion, we have used an in vitro model of BBB composed of human endothelial hCMEC/D3 cells that can form tight junctions. These cells were cultivated on Transwell inserts and placed above human neuronal cells. Using this system, we show that YFV FNV cross the BBB more efficiently than YFV 17D, suggesting that YFV FNV is more neuroinvasive than YFV 17D. This observation can explain the higher post-vaccine encephalitis risks associated with YFV FNV vaccine compared to YFV 17D vaccine. We also confirmed that JEV SA14-14-2 vaccine strain is less neuroinvasive than JEV RP9.We also examined how JEV crosses the BBB and the endothelial cell response following JEV treatment. We show that both JEV RP9 and SA14-14-2 are able to cross the BBB without infecting its endothelial cells and without disrupting the BBB. Preliminary results suggest that JEV RP9, but not JEV SA14-14-2, crosses the BBB by dynamin-dependant transcytosis. Transcriptomic analysis of endothelial cells treated by either virus show slight, but significant, differences in regulation of genes implicated in several pathways associated with CNS diseases

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Silveira, Roberta Maraninchi. « Localização subcelular do vírus da Zika durante a infecção em células humanas ». Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17136/tde-13092018-105525/.

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O vírus da Zika (ZIKV) é um arbovírus emergente da família Flaviviridae, do gênero Flavivirus transmitido por mosquitos Aedes. Apesar da sua importância emergente na saúde pública, ainda pouco se conhece sobre os mecanismos moleculares envolvidos no ciclo replicativo do ZIKV em célula humanas. Assim, o objetivo geral deste estudo foi caracterizar a distribuição subcelular do ZIKV na célula hospedeira e elucidar fatores celulares que regulam o tráfego intracelular de proteínas envolvidos nesses processos. Mais especificamente, determinar os compartimentos celulares que servem de plataforma de montagem para o ZIKV. Além disso, também verificar se o funcionamento da maquinaria Endosomal Sorting Complexes Required for Transport (ESCRT) é requerido no ciclo replicativo de ZIKV. Para identificar a localização subcelular do ZIKV, foram utilizados diferentes marcadores celulares, e, de acordo com os resultados, foi demonstrado que com 3 horas pós infecção (h. p. i.) ocorre colocalização de proteínas do ZIKV com um marcador de endossomo primário, enquanto que com 15h p.i. já é possível detectar proteínas virais no Retículo Endoplasmático (RE). Subsequentemente, com 27h p.i. o ZIKV direciona-se para o complexo de Golgi. Juntos, esses resultados indicam o direcionamento do ZIKV através da via secretória ao longo do tempo. Além disso, foi testado o envolvimento da maquinaria dos ESCRTs por meio do silenciamento da expressão da proteína TSG101 de ESCRT-I em células infectadas com ZIKV. Os resultados obtidos, sugerem que ESCRT-I tem participação importante na replicação do ZIKV, ocorrendo a diminuição dos títulos virais quando TSG101 é depletada da célula. Em conjunto, os resultados permitem concluir que ao longo da infecção o ZIKV encontrase associado aos compartimentos da via secretória inicial (RE e complexo de Golgi), e que a proteína TSG101 de ESCRT-I exerce papel importante na replicação viral. Sendo assim, esse estudo possibilitou um melhor entendimento sobre a dinâmica de replicação do ZIKV em células humanas.
Zika virus (ZIKV) is an arbovirus of the Flaviviridae family, of the genus Flavivirus that is transmitted by Aedes mosquitoes. Despite its emerging importance in public health, little is known about the molecular mechanisms involved in the replicative cycle of ZIKV in human cells. Thus, the general objective of this study was to characterize the subcellular distribution of the ZIKV in the host cell and to elucidate cellular factors that regulate the intracellular trafficking of proteins involved in these processes. More specifically, to determine the cellular compartments that serve as assembly platforms for the ZIKV. In addition, the study aimed to verify if the functioning of the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery is required in the replicative cycle of ZIKV. In order to identify the subcellular localization of ZIKV, different intracellular markers were used, and, according to the results, it was demonstrated that at 3 hours post infection (h. p. i.) ZIKV proteins colocalize with an early endosome marker, whereas within 15h p.i. it is already possible to detect newlysynthesized viral proteins in the endoplasmic reticulum (ER). Subsequently, within 27h p.i., the ZIKV is directed to the Golgi complex. Together, these results delineate the targeting of ZIKV proteins through the secretory pathway over time. In addition, the involvement of the ESCRT machinery was tested by knocking down the expression of ESCRT-I protein TSG101 in ZIKV-infected cells. The results obtained suggest that ESCRT-I plays an important role in ZIKV replication, with viral titers decreasing when TSG101 levels are depleted in the cell. Together, the results allow us to conclude that ZIKV is associated with the initial secretory pathways (RE and Golgi complex) throughout the infection, and that the ESCRT-I TSG101 protein plays an important role in viral replication. Thus, this study contributes to a better understanding of the dynamics of ZIKV replication in human cells.

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Grard, Gilda. « Génomique et évolution des flavivirus transmis par les tiques et découverte d'un nouveau lignage du genre flavivirus ». Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX20679.

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Gollins, S. W. « Mechanisms of flavivirus neutralization and cellular infection ». Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355752.

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Dayaraj, Cecilia. « Molecular and immunological studies on flavivirus virulence ». Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279888.

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Carney, Jennifer. « Viral Determinants of Flavivirus Neurotropism in Humans ». Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526956.

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Pacca, Carolina Colombelli. « Screening de novos antivirais inibidores de flavivirus ». Faculdade de Medicina de São José do Rio Preto, 2013. http://bdtd.famerp.br/handle/tede/201.

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Introduction. Arboviruses, arthropod-borne viruses, are frequently associated with human outbreaks and represent a serious health problem. The genus Flavivirus, which includes both the Yellow Fever Virus (YFV) and Saint Louis Encephalitis Virus (SLEV), are important pathogens that result in high morbidity and mortality rates worldwide. In Brazil, YFV has a sylvatic cycle and occurs annually, despite the efficiency of the vaccine. Saint Louis Encephalitis is an infectious illness that can cause acute fever caused by SLEV, which is widely distributed in the Americas. The emergence of SLEV became a serious concern after the first related outbreak in Brazil in 2006, in the city of Sao Jose do Rio Preto. There is no specific antiviral drug for these viruses, only supporting treatment that can alleviate the symptoms and prevent complications. The need to develop effective and safe antiviral drugs is indispensable for the treatment of these infections. Objective. The aim of this work was to identify new possible antiviral drugs against the arboviruses that can cause acute fever and encephalitis (YFV and SLEV) and to evaluate the capacity of inhibition of these compounds in ABR mice. Material and Methods. Plaque reduction assay, flow citometry, immunofluorescence and cellular viability were used to test the compounds in vitro. ABR mice were inoculated with YFV, and the biological samples were tested for the presence of the virus through the use of plaque reduction assay and qPCR. Neutralization assay was also performed. Results. Treated cells showed efficient inhibition of viral replication at concentrations that presented minimal toxicity to the cells. The assays showed that ftalyl-tiazole and fenoxytiosemicarbazone were more effective, and that they reduced viral replication by 60% and 75% for YFV and SLEV, respectively. The analysis also revealed that the ABR mice inoculated with YFV had histopathological alterations in the liver; however, the samples did not present viral title. Neutralization assay showed a high concentration of antibodies in the serum. Conclusion. The inhibitions of viral replication were confirmed through the use of some assays in vitro, and the effectiveness of the selected compounds show that they are an option in the treatment of these viruses. More detailed studies are needed to determine the mechanism of action of these molecules. The mice were found to have histopathological alterations, which indicates viral infection; however, they also presented with high concentrations of antibodies. More studies about animal models are necessary to make in vivo experiments.
Introdução: Os arbovírus, vírus transmitidos por artrópodes, são freqüentemente associadas a surtos em seres humanos e representam um problema sério de saúde pública. Os vírus pertencentes ao gênero Flavivirus, tais como vírus da Febre Amarela (YFV) e vírus da Encefalite de Saint Louis (SLEV), são importantes patógenos que podem causar alta taxa de morbidade e mortalidade no mundo. No Brasil, YFV é mantido em ciclo silvestre notificados anualmente, a despeito da segurança e eficiência da vacina. A encefalite de Saint Louis é uma doença infecciosa febril aguda causada pelo SLEV amplamente distribuída nas Américas. A emergência do SLEV passou a ser um fato preocupante no Brasil a partir da constatação do primeiro surto no país em 2006, na cidade de São Jose do Rio Preto. Não existe tratamento específico para estas viroses, somente tratamento de suporte para ajudar a aliviar os sintomas e prevenir complicações. Desta forma, há uma grande necessidade de que sejam desenvolvidos antivirais efetivos e seguros para o tratamento destas infecções. Objetivos: O objetivo deste trabalho foi identificar potenciais compostos antivirais contra os arbovírus causadores de doença febril aguda e encefalites (YFV e SLEV) in vitro e avaliar a capacidade de inibição da replicação viral dos compostos in vivo em camundongos ABR. Materiais e Métodos: Para tanto, foram realizados ensaios de redução de placas, citometria de fluxo, imunofluorescencia, bem como testes de viabilidade celular para as analises in vitro. Além disto, camundongos ABR foram inoculados com YFV e seus materiais biológicos testados para a presença de partículas virais por ensaio de redução de placas e qPCR. Adicionalmente, foi realizado ensaio de neutralização do soro dos animais. Resultados: Celulas tratadas com os compostos mostraram eficiente inibição da replicação viral em concentrações que apresentam baixa citotoxicidade. Os ensaios mostraram que derivados de ftalyl-tiazole e fenoxytiosemicarbazone foram os mais eficazes na ação antiviral, apresentando redução de 60% e 75% para YFV e SLEV, respectivamente. Camundongos ABR inoculados com YFV apresentaram alterações histológicas no fígado, entretanto, não foi constatado título viral nas amostras testadas. O ensaio de neutralização mostra altas concentrações de anticorpos no soro dos animais. Conclusões: A inibição da replicação foi comprovada por vários ensaios in vitro evidenciando as moléculas como potentes alternativas para o tratamento dos vírus. Mais estudos são necessários para a determinação do mecanismo de ação destas moléculas. Os camundongos apresentaram alterações histopatológicas sendo um indicativo de infecção, entretanto, apresentam altas taxas de anticorpos. Mais estudos sobre modelo animal são necessários para a realização de ensaios in vivo.

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Singethan, Katrin. « Untersuchungen zur Inhibition Paramyxo- und Flavivirus-induzierter Membranfusion ». kostenfrei, 2009. http://www.opus-bayern.de/uni-wuerzburg/volltexte/2009/3634/.

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Cunha, Mariana Sequetin. « Validação e uso de transcrição reversa seguida da reação em cadeia pela polimerase em tempo real (RT-qPCR) para a vigilância e diagnóstico de flavivírus transmitidos por mosquitos circulantes no Brasil ». Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-16102018-113026/.

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Os flavivírus são considerados uma séria ameaça à saúde pública em diversas partes do mundo, pois muitos são agentes altamente patogênicos a seres humanos e animais, tais como os vírus da febre amarela, vírus do Oeste do Nilo, vírus da encefalite japonesa e vírus da dengue, capazes de causar encefalites ou febres hemorrágicas em seus hospedeiros. Muitos deles têm avançado a diferentes regiões geográficas onde sua circulação não havia sido detectada previamente, causando novos surtos. O diagnóstico clínico destas infecções é, muitas vezes, difícil, devido ao grande número de sintomas apresentados, que podem se confundir com outras enfermidades de diferentes causas etiológicas. Os principais métodos diretos utilizados atualmente no Brasil para detecção destes vírus são a inoculação intracerebral em camundongos neonatos, inoculação em culturas de células e RTPCR específica. O presente trabalho tem como objetivos avaliar a sensibilidade e validar a detecção dos vírus pertencentes ao gênero Flavivirus circulantes no Brasil por meio de uma reação single de RT-PCR em tempo real e implementá-la, tanto na rotina diagnóstica de casos com suspeita de arbovirose como na pesquisa de amostras de campo para monitoramento viral. Amostras dos flavivírus padrões da Febre Amarela, Bussuquara, Iguape, Ilheus, Encefalite de Saint Louis, Cacipacore e Zika foram quantificados por titulação em unidades formadoras de placa (UFP) ou TCID50 para se avaliar os limites de detecção para cada um deles por RT-qPCR que detecta o gênero Flavivirus. Os limites encontrados variaram de 0,01 UFP, para o vírus Ilheus, a 1 UFP, para os vírus da Febre Amarela e Iguape, e 1x101,6 TCID50/100µL para o vírus Bussuquara. Além disso, o presente trabalho foi capaz de identificar, após sequenciamento de cDNA gerado, os vírus Zika, isolado de um paciente febril, e os vírus Ilheus e Iguape, isolados a partir de diferentes espécies de Culicídeos, após uma única reação de RT-qPCR, e um possível novo flavivírus específico de insetos, isolado de mosquitos Aedes coletados em Guapiaçu, São Paulo. Não houve sinal de amplificação para os Alphavirus Mayaro e Chikungunya. O presente protocolo mostrou-se com alta sensibilidade e especificidade, podendo dessa forma ser utilizado para o diagnóstico diferencial dos diferentes flavivírus que ocorrem no Brasil, bem como para estudos de monitoramento viral em animais sentinelas e vetores, colaborando dessa forma com a saúde pública. Pode-se, ainda, detectar possíveis novos vírus específicos de artrópodes
Flaviviruses are considered a serious threat to public health in many parts of the world, as many are highly pathogenic to humans and animals, such as Yellow Fever virus, West Nile virus, Japanese encephalitis virus and dengue virus, which are capable of causing encephalitis or hemorrhagic fever in their hosts. Many of them have spread to different geographic regions where their circulation had not been detected previously, causing new outbreaks. Diagnosis of these infections is often difficult, due to the large number of symptoms presented, which can be confused with other diseases of different etiological causes. The main direct methods currently used in Brazil for detecting these viruses are intracerebral inoculation in neonatal mice, inoculation in cell cultures and specific RT-PCR. The present work aims to evaluate the sensitivity and validate the detection of viruses belonging to the genus Flavivirus circulating in Brazil through a single real-time RT-PCR reaction and to implement it, both in the diagnostic routine of cases with arbovirus suspicions and in field samples for viral monitoring. Samples of the standard flaviviruses Yellow Fever, Bussuquara, Iguape, Ilheus, Saint Louis Encephalitis, Cacipacore and Zika were quantified by titration by plaque forming units (UFP) or TCID50 to evaluate the detection limits for each of them by RT- qPCR that detects genus Flavivirus. The limits found ranged from 0.01 PFU for Ilheus virus to 1 PFU for Yellow Fever and Iguape viruses and 1x101.6 TCID50 / 100L for the Bussuquara virus. In addition, the present work was able to identify, after cDNA sequencing Zika virus, isolated from a febrile patient, and both Ilheus and Iguape viruses, isolated from different species of Culicidae, and a possible new insect-specific flavivirus, isolated from Aedes mosquitoes collected in Guapiaçu, São Paulo. The Alphaviruses Mayaro and Chikungunya were not amplified. The present protocol shoed high sensitivity and specificity, and therefore it may may be used for the differential diagnosis of the different flaviviruses that occur in Brazil, as well as for viral monitoring studies in sentinel animals and vectors, thus collaborating with public health. It is also possible to detect new flavivirus that are arthopode-specific.

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Livres sur le sujet "Flaviviru"

Gregory, Bock, Goode Jamie, Novartis Foundation et Novartis Institute for Tropical Diseases., dir. New treatment strategies for dengue and other flaviviral diseases. Chichester : John Wiley & Sons, 2006.

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Shi, Pei-Yong. Molecular virology and control of flaviviruses. Norfolk, UK : Caister Academic Press, 2012.

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Bock, Gregory, et Jamie Goode, dir. New Treatment Strategies for Dengue and Other Flaviviral Diseases. Chichester, UK : John Wiley & Sons, Ltd, 2006. http://dx.doi.org/10.1002/0470058005.

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Ruzek, Daniel, dir. Flavivirus Encephalitis. InTech, 2011. http://dx.doi.org/10.5772/847.

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Tkachev, Sergey, dir. Non-Flavivirus Encephalitis. InTech, 2011. http://dx.doi.org/10.5772/1740.

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Velásquez Serra, Glenda. Garrapatas : Vectores de Flavivirus. CIDEPRO EDITORIAL, 2019. http://dx.doi.org/10.29018/978-9942-823-09-0.

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Advances in Flavivirus Research. MDPI, 2017. http://dx.doi.org/10.3390/books978-3-03842-487-1.

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Molecular Biology of Flavivirus. Taylor & Francis, 2006.

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Schlesinger, Milton J., et Sondra Schlesinger. Togaviridae and Flaviviridae. Springer, 2012.

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Goode, Jamie A., et Gregory R. Bock. New Treatment Strategies for Dengue and Other Flaviviral Diseases. Wiley & Sons, Incorporated, John, 2006.

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Chapitres de livres sur le sujet "Flaviviru"

Contigiani, Marta S., Luis A. Diaz et Lorena Spinsanti. « Flavivirus ». Dans Arthropod Borne Diseases, 73–88. Cham : Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-13884-8_6.

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Harnett, Gerald B., et Julia A. Cattell. « Flavivirus ». Dans PCR for Clinical Microbiology, 241–44. Dordrecht : Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-9039-3_34.

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Gooch, Jan W. « Flavivirus ». Dans Encyclopedic Dictionary of Polymers, 893. New York, NY : Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_13767.

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Westaway, Edwin G. « Flavivirus‡ ». Dans The Springer Index of Viruses, 461–71. New York, NY : Springer New York, 2011. http://dx.doi.org/10.1007/978-0-387-95919-1_67.

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Reid, Hugh W., Herbert Weissenböck et Károly Erdélyi. « Flavivirus Infections ». Dans Infectious Diseases of Wild Mammals and Birds in Europe, 128–45. Oxford, UK : Wiley-Blackwell, 2012. http://dx.doi.org/10.1002/9781118342442.ch9.

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Glowacka, Ilona. « Flaviviren ». Dans Medizinische Mikrobiologie und Infektiologie, 607–16. Berlin, Heidelberg : Springer Berlin Heidelberg, 2020. http://dx.doi.org/10.1007/978-3-662-61385-6_55.

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Falke, D. « Flaviviren ». Dans Springer-Lehrbuch, 463–68. Berlin, Heidelberg : Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24167-3_56.

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Schomburg, Dietmar, et Dörte Stephan. « Flavivirin ». Dans Enzyme Handbook 15, 757–60. Berlin, Heidelberg : Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-58948-5_154.

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Glowacka, I. « Flaviviren ». Dans Springer-Lehrbuch, 467–73. Berlin, Heidelberg : Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-48678-8_56.

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Yu, Yufeng, Lulu Si et Yu Meng. « Flavivirus Entry Inhibitors ». Dans Advances in Experimental Medicine and Biology, 171–97. Singapore : Springer Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-8702-0_11.

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Actes de conférences sur le sujet "Flaviviru"

Chaley, M. B., Zh S. Tyulko et V. A. Kutyrkin. « Specifics of Coding Sequences in the Flavivirus Genomes ». Dans Mathematical Biology and Bioinformatics. Pushchino : IMPB RAS - Branch of KIAM RAS, 2018. http://dx.doi.org/10.17537/icmbb18.10.

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« Recognition of flavivirus species on the base of coding genome sequences ». Dans Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-091.

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Chaley, M. B., Zh S. Tyulko et V. A. Kutyrkin. « Fast Method to Recognize Flavivirus Species after Sequencing the Viral Genome ». Dans Mathematical Biology and Bioinformatics. Pushchino : IMPB RAS - Branch of KIAM RAS, 2020. http://dx.doi.org/10.17537/icmbb20.12.

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woo Kim, Chan, Se Hwan Ahn et Taeseon Yoon. « Comparison of flavivirus using datamining-Apriori, K-means, and decision tree algorithm ». Dans 2017 19th International Conference on Advanced Communication Technology (ICACT). IEEE, 2017. http://dx.doi.org/10.23919/icact.2017.7890130.

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Martins, Raquel, Carolina Cajaraville, Fernando Conte et Márcia Arissawa. « Optimized production of monoclonal antibody used in Flavivirus immunoassays for different projects of vaccine development ». Dans II Seminário Anual Científico e Tecnológico em Imunobiológicos. Instituto de Tecnologia em Imunobiológicos, 2014. http://dx.doi.org/10.35259/isi.sact.2014_28652.

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Silva, Thalita Barcelos, Luiza Helena Angarten Ferraz De Carvalho, Dhullya Eduarda Resende Santos, Júlia Emanuelle Macedo Noleto et Hanstter Hallison Alves Rezende. « O ESTUDO DOS FLAVIVÍRUS PELA BIOINFORMÁTICA E A IMPORTÂNCIA NA BUSCA POR ANTIVIRAIS ». Dans I Congresso de Engenharia de Biotecnologia. Revista Multidisciplinar de Educação e Meio Ambiente, 2021. http://dx.doi.org/10.51189/rema/1369.

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Introdução: Flavivírus é um gênero de vírus que apresenta grande incidência de infecção em todo o mundo, como Dengue, Febre Amarela e Zika, sendo elas doenças emergentes. Eles são arbovírus, o hospedeiro intermediário é um artrópode responsável por transmitir os vírus, sendo o principal vetor o mosquito Aedes aegypti. Diversos estudos buscam encontrar fármacos que possam agir como antivirais e uma das formas utilizadas é a partir da bioinformática. Ela analisa de maneira tridimensional, por estudo computacional, sequências estruturais importantes, buscando proteínas chave, enzimas e inibidores na tentativa de encontrar formas de interações entre elas e fármacos, possibilitando o desenvolvimento de potenciais antivirais para um tratamento eficaz. Objetivo: Realizar uma revisão bibliográfica sobre a importância da bioinformática nas buscas por fármacos que possam tratar doenças causadas por Flavivírus. Material e métodos: Trata-se de uma revisão de literatura realizada a partir da seleção e análise de 5 artigos, publicados entre os anos de 2015 a 2020, sendo coletados nas plataformas de pesquisa Google Acadêmico e Scielo, encontrados utilizando os descritores: Antivirais, Bioinformática, Dengue e Flavivírus. Resultados: Infecções como Dengue, Zika e Febre Amarela causam preocupação, principalmente por serem sazonais e com grande índice de infecção. A epidemia dessas doenças, preocupa os pesquisadores em decorrência ao alto número de infectados na última década e por não haver um tratamento eficaz e definitivo, somente paliativo. Estudos têm sido realizados com maior intensidade, principalmente com a utilização de modelagem molecular para determinar os sítios de ligação e o complexo droga-receptor. Um estudo in sílico utilizou o complexo protease NS3-NS2B em conjunto com uma molécula inibidora (BznKRR-H cristalografada), e por meio da bioinformática, calculou a energia de ligação existente entre cada aminoácido da estrutura e a interação do inibidor BznKRR-H, a fim de determinar a viabilidade de uma ação farmacológica eficiente contra o vírus, para partir para um estudo in vitro e in vivo. Conclusão: A bioinformática tem grande importância na busca por tratamentos, pois as inovações tecnológicas possibilitam a avaliação de possíveis antivirais, principalmente com a busca dos complexos droga-inibidor, analisando quais apresentariam uma maior eficácia contra o vírus.

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Lima, Michelle, Paloma Pêgo, Gabriel Silva et Salvatore De Simone. « Identification of targeted epitopes of yellow fever virus based on homology with other species of flavivirus ». Dans V Seminário Anual Científico e Tecnológico. Instituto de Tecnologia em Imunobiológicos, 2017. http://dx.doi.org/10.35259/isi.sact.2017_26145.

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Radzol, A. R. M., Khuan Y. Lee, W. Mansor et I. S. Omar. « PCA criterion for SVM (MLP) classifier for flavivirus biomarker from salivary SERS spectra at febrile stage ». Dans 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2016. http://dx.doi.org/10.1109/embc.2016.7592146.

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Nandy, Ashesh, Sumanta Dey, Proyasha Roy, Subhas Basak et Sukhen Das. « Comparison of Base Distributions in Dengue, Zika and Other Flavivirus Envelope and NS5 Genes ». Dans MOL2NET 2017, International Conference on Multidisciplinary Sciences, 3rd edition. Basel, Switzerland : MDPI, 2017. http://dx.doi.org/10.3390/mol2net-03-04966.

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Silva, Carla Pinheiro da. « ESTUDO DA RESPOSTA DE ANTICORPOS PARA FLAVIVIRUS NA POPULAÇÃO BRASILEIRA FRENTE À EMERGÊNCIA DO VZIK NO PAÍS ». Dans VIII Seminário de Integração Científica da Universidade do Estado do Pará, chair Lívia Caricio Martins. Universidade do Estado do Pará, 2019. http://dx.doi.org/10.31792/21759766.viiisic.2019.226-230.

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Rapports d'organisations sur le sujet "Flaviviru"

Paul, Satashree. Flavivirus and its Threat. Science Repository, mars 2021. http://dx.doi.org/10.31487/sr.blog.30.

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A number of studies found that the virus can activate the endothelial cells and affect the structure and function of the blood?brain barrier, promoting immune cell migration to benefit the virus nervous system target cells infected by flaviviruses.

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Fournier, Maurille J., et Thomas L. Mason. Structure and Expression of Genes for Flavivirus Immunogens. Fort Belvoir, VA : Defense Technical Information Center, janvier 1992. http://dx.doi.org/10.21236/ada252662.

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