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Ewing, Stephen Michael George. "Herpes simplex virus type 1 infection of dendritic leucocytes." Thesis, University of Oxford, 1992. http://ora.ox.ac.uk/objects/uuid:e83750b1-3aa7-452e-a876-be51690252be.
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McBride, Brian William. "Mucosal immune responses induced by herpes simplex virus infection." Thesis, University of Southampton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254770.
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Brown, Elizabeth L. "Consequences of genital herpes simplex virus infection among vulnerable populations /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/10885.
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Sayers, Charlotte. "Herpes simplex virus type 1 infection of human keratinocyte cells." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11112.
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Infection of herpes simplex virus type 1 (HSV-1) begins at the epidermis, a stratified layer composed primarily of keratinocytes. The physiologically relevant cell type for the study of HSV-1 assembly is therefore the human keratinocyte. Nonetheless, relatively little is known about the replication of HSV-1 in this natural host cell. Comparison of virus growth in monolayers of keratinocyte cells and Vero cells, a routinely used cell line for HSV-1 studies, revealed that these keratinocytes support a more productive virus replication than Vero cells. Furthermore, newly assembled virus is produced more rapidly in keratinocytes and this enhancement occurs prior to, or upon the initiation of immediate early gene transcription. This augmented replication in keratinocytes can be at least partially attributed to the method of entry of the virus. We have found by penetration assays and electron microscopy that the virus is able to penetrate keratinocyte cells much more rapidly than Vero cells. We have also shown that the virus entry mechanism is more efficient at lower temperatures in nTERT cells, with virus entering cells at temperatures as low as 7°C. Additionally preliminary work implies that depletion of one of the herpes virus entry receptors, Nectin-1, does not affect entry into nTERT cells, whereas entry is reduced up to 65% in HeLa cells. Taken together, these results imply a role for other entry receptors, possibly as yet unidentified, in the entry of human keratinocyte cells. This work also identifies a role for cellular Rab proteins, GTPases essential for the regulation of vesicle trafficking, in HSV-1 infection of keratinocytes. In particular Rab6, which was also found to play a role in infected HeLa cells (Elliott Group), appears to have a similar function in both these cells and together support a model for HSV-1 morphogenesis involving Rab-regulated vesicle trafficking of viral glycoproteins to the cell surface. Several other Rabs identified by this screen now provide interesting opportunities to elucidate further roles of Rab proteins in HSV-1 infection of keratinocyte cells. This project has broadly characterised the replication of HSV-1 in keratinocyte cells and explored the role of Rab GTPases in virus trafficking within keratinocytes - a cell type that is physiologically relevant to infection.
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Williams, N. A. "The role of Langerhans cells in infection with herpes simplex virus." Thesis, University of Bristol, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235240.
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LABAUNE, JEAN-MARC. "Infection herpetique neonatale : etude lyonnaise sur 5 ans." Lyon 1, 1994. http://www.theses.fr/1994LYO1M208.
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Simmonds, Peter. "Detection of antibody responses to infection with herpes simplex virus and human immunodeficiency virus." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/26933.
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Lee, Jennifer Sohn. "Epigenetic Regulation of Lytic and Latent Herpes Simplex Virus 1 Infection." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467322.
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Epigenetic regulation plays a major role in whether the herpes simplex virus 1 (HSV-1) will initiate viral gene expression and lytic infection or instead suppress its gene expression and establish a latent infection. Prior to this study, it was known that cells respond to naked DNA by assembling chromatin to silence foreign genetic material. However, during lytic infection of epithelial cells, viral proteins VP16 and ICP0 have been implicated in limiting chromatin association and promoting euchromatic histone modifications on the HSV-1 genome. We hypothesized that the viral genome would also be subject to silencing by heterochromatin modification during lytic infection. To test this we examined the association of chromatin and heterochromatic modifications during lytic infection with WT viruses and ICP0-null mutant viruses. We found that heterochromatin modifications H3K9me3 and H3K27me3 associate initially with all viruses, but were removed rapidly during infection with WT HSV-1. ICP0-null viruses were not able to remove histones or heterochromatin, indicating a role for ICP0 in reversing epigenetic silencing.
In latent infection, HSV-1 undergoes epigenetic silencing as a means to suppress gene expression and persist in neurons. Surprisingly, in this study, we find that ICP0-null viruses accumulate less heterochromatin on lytic gene promoters relative to WT viruses. This suggests that ICP0 may function to promote infection of neurons, or assist in the establishment or maintenance of latent infection.
Additionally, during latency the viral genome maintains active expression from the latency-associated transcript (LAT) region, and this region retains markers of euchromatin that are excluded from the lytic viral genes. The insulator protein, CTCF, binds to a site downstream of this region between the LAT and ICP0 promoters. We find that during latent infection, deletion of this site promoted accumulation of H3K27me3 at the LAT promoter and reduced reactivation competence of the virus, but surprisingly enhanced LAT expression. This suggests that CTCF balances epigenetic repression to promote latency and maintain reactivation competence. In summary, this dissertation suggests that during lytic infection HSV reverses cell-mediated epigenetic repression and promotes viral gene expression, while during latency, the virus co-opts epigenetic mechanisms to maintain a silenced but poised genome.Medical Sciences
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Littlejohn, Emma Sophie Vout. "The Sensitivity of Adenovirus and Herpes simplex virus to Honey." The University of Waikato, 2009. http://hdl.handle.net/10289/2804.
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Honey has been used for centuries as a medicine to treat various ailments and infections. A large amount of research has established that honey has potent antibacterial activity. However, the sensitivity to honey of viral species that cause infections has been studied in only a small number of cases. The aim of this study was to obtain data to clarify and extend knowledge obtained from these previous studies of honey's antiviral activity, and especially study those viruses that cause localised infections which have limited or no therapy available, which are suitable to treatment with topically applied honey. The susceptible A549 cell line and viral isolates of Adenovirus serotypes 1, 3, and 8, and Herpes simplex virus serotypes 1 and 2, were provided by the Waikato Hospital Virology Laboratory. A number of types of honey were investigated from a range of sources: Manuka honey with high concentrations of methylglyoxal, unique manuka factor activity, and phenolics, Honeydew and Rewarewa honeys which have high antioxidant activity, and Ling Heather honey which is high in phenolic compounds. These honeys were selected due to their range of characteristic activities in order to make comparisons with antiviral activity. A variety of tests using cell culture were developed to evaluate the sensitivity of the viruses to whole honey. Each test scored and monitored the development of morphological changes to the cells, to observe whether the honey treatment can prevent the development of these changes known as viral cytopathic effect. These included tests for: protection, in which the cells were pre-treated with, and iii incubated either with or without honey; prevention, where honey was used to treat infected cells, and in plaque reduction assays, to examine whether it can reduce the resultant number of plaques; and neutralisation, in which the virus was directly exposed to the honey for a defined period. It was found with each type of test using cell culture that many of the honeys studied can lower the severity of viral cytopathic effect or delay its onset compared with the development observed with virus that was not treated with honey. This can suggest that the antiviral activity may be a feature of more than one type of honey. In general the antiviral effect increased with the concentration of honey and time the virus was exposed to it. Manuka honey M116 at a concentration of 10% was effective in preventing the development of viral cytopathic effect of each of virus, after the viruses at concentrations in excess of the tissue culture infectious dose had been exposed to the honey for 8 hours. Enzyme-linked immunosorbant assays were used to measure the effect the successful treatments found in the extended neutralisation experiments had on viral surface proteins necessary for viral entry into the cells. The results using this technique suggested that there was very little virus present in the samples that had been treated with honey and with the untreated virus. Therefore it could not be shown whether the honey was acting via this mechanism. It is concluded from the findings in this study that honey is likely to be an effective antiviral treatment for the therapy of localised viral infections, this needs to be verified by clinical trials.
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Laycock, K. A. "Herpes simplex virus gene expression in establishment and maintenance of latent infection." Thesis, University of Bristol, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234807.
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Cheung, Peter. "Brefeldin A arrests the maturation and egress of herpes simplex virus particles during infection." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/29798.
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Herpes Simplex Virus (HSV) requires the host cell secretory apparatus for the maturation and egress of newly synthesized viral particles. Not only do viral glycoproteins rely on the host ER and Golgi compartments for their proper processing, it is believed that enveloped particles are transported through these same organelles for their export out of the cells. Brefeldin A (BFA) is a compound that induces retrograde movement of material from the Golgi apparatus to the ER and causes the disassembly of the Golgi complex. In this study, the effects of BFA on the propagation of HSV-1 in infected cells were examined. Release of viral particles from infected cells was inhibited by as little as 1 µg/ml BFA. Further analysis revealed that BFA did not affect the normal assembly of viral nucleocapsids, but did block the movement of newly-enveloped particles from the nucleus into the cytoplasm. Naked nucleocapsids were found in the cytoplasm of infected cells treated with BFA, however, these particles were neither infectious, nor were they released from the cells. Although BFA altered the distribution of viral glycoproteins in infected cells, this alteration was reversed within 2 hours after the removal of BFA. In contrast, the BFA-induced blockage to viral release was not fully reversed after BFA was removed and cells were allowed to recover in fresh medium for 3 hours. These findings indicate that the BFA-induced retrograde movement of material from the Golgi complex to the ER early in infection arrests the ability of the host cell to support the
maturation and egress of enveloped viral particles. Furthermore, exposure of infected cells to BFA during the exponential release phase of the viral life cycle can cause irreversible damage to the egressing particles. This suggests that productive growth of HSV-1 in infected cells relies on a series of events that, once disrupted by agents such as BFA, cannot be easily reconstituted.Science, Faculty of
Microbiology and Immunology, Department of
Graduate
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Gasilina, Anjelika. "Herpes Simplex Virus-1: Crosstalk Between the Host Immunity and the Virus during Infection, Latency and Reanimation." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444615.
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Herbein, Georges. "L'infection à Herpesvirus humain type 6 (HHV-6) chez les transplantés : une étude rétrospective de 32 patients." Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR1M098.
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Gor, Dehila. "Investigation of herpes simplex virus and Cytomegalovirus infection in the immunocompromised host." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323037.
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Ramaswamy, Meghna. "The epidemiology and natural history of genital herpes simplex virus (HSV) infection." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445811/.
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Genital infection with herpes simplex virus type 2 (HSV -2) is increasingly common worldwide. The aims of this thesis were to investigate the epidemiology and natural history of genital herpes among GUM attendees with symptomatic genital herpes, and among HIV-l infected individuals. In our study of GUM attendees in the UK, we demonstrated HSV -1 to account for 9% of first episodes of genital herpes. These findings are in contrast with observations made elsewhere in the UK, where HSV -1 has accounted for >50% of first-episode cases. As most individuals with genital HSV -2 infection remain clinically misdiagnosed, the need for improved diagnostic methods to detect genital HSV infection is warranted. We compared the performance of virus culture and PCR in patients clinically diagnosed with genital herpes. PCR increased HSV detection in patients with both early and late presentations and in first and recurrent diseases. PEG precipitation was the most sensitive specimen preparation method of choice. A HSV positive PCR was also associated with heterosexuals, early presentation, and visible genital ulceration. HSV -1 and HSV -2 genital infections were also associated with white and black ethnicity respectively. This suggests that host susceptibility and behavioural factors may influence the epidemiological patterns of genital herpes. Current data support the use of HSV type-specific serology and PCR to diagnose HSV infections. In addition to PCR, we evaluated the performance of type-specific serology (HerpeSelect EIA, Focus Technologies, Cypress, California, USA) for the diagnosis of HSV infection. Our findings indicated that increasing the assay cut-off from 1.1 to 3.1 increased specificity and maintained sensitivity. By performing an inhibition EIA using an inhibition value of ~60% we minimised false positive results from Ugandan and Kenyan sera. Recent data has implicated HSV-2 as a co-factor in HIV transmission. We therefore investigated the seroepidemiology of HSV infection among 850 HIV-infected individuals. HSV-2 seroprevalence was 63% and increased with age and was associated with female gender, heterosexuals and black ethnicity. A follow-up of 123 HSV-2 seronegative persons revealed a HSV -2 seroconversion rate of 10% which was associated with HPV infection and gonorrhoea. Only 21 % of the seroconverters received a clinical diagnosis of genital herpes, and this was more likely in persons diagnosed HIV -1 positive before 1997 (preHAART era). To investigate the effects of HAART on HSV-specific immunity, we studied the kinetics of HAART-induced reconstitution of HSV-specific T-cell responses in HIV-l infected persons at different stages of clinical disease using an ELISPOT assay. Successful HAART proved to resolve HSV-specific immunity restoration which coincided with HAART-induced CD4 gain. HSV-specific IFN-y responses correlated with CD4 counts. Responses similar to those of HIV -negative healthy controls were seen at CD4 counts >450 cells/mm3.
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Collins, Terry Cordell. "The effect of HSV-2 infection on the expression of cellular mitochondrial aspartate aminotransferase." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266539.
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Nicholls, S. M. "Herpes simplex virus infection in sensory ganglia of mice in vivo and in vitro." Thesis, University of Bristol, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379502.
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Linard, de Guertechin Morgane. "Virus Herpès Simplex de type 1 : une cible potentielle pour la prévention de la maladie d’Alzheimer ?" Thesis, Bordeaux, 2021. http://www.theses.fr/2021BORD0118.
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Malgré de nombreuses avancées concernant la compréhension des mécanismes impliqués dans la maladie d’Alzheimer (MA), son étiologie précise reste inconnue aujourd’hui. Cependant, un nombre croissant d’articles suggèrent que l’implication du virus Herpès Simplex de type 1 (HSV-1) pourrait expliquer à la fois les séquences topographique et temporelle ainsi que le type d’atteintes retrouvées dans la MA. En effet, HSV-1 est un virus neurotrope retrouvé dans le cerveau de personnes âgées et présentant un tropisme particulier pour les zones impliquées dans la MA. Il est également capable de se propager de cellules en cellules. Durant la vie, HSV-1 reste à l’état latent dans le corps et est capable de se réactiver périodiquement. Avec l’avancée en âge, le déclin du système immunitaire pourrait permettre la survenue de réactivations plus fréquentes et/ou plus intenses du virus, expliquant ainsi potentiellement la survenue tardive et progressive de la MA. De plus, les principaux marqueurs anatomopathologiques de la MA (lésions amyloïde, tau, neuroinflammation) peuvent être induits in vitro et chez l’animal par l’inoculation du virus HSV-1 et l’accumulation du peptide aβ pourrait être due à son implication dans la défense antimicrobienne. Dans cette thèse, afin de tester cette hypothèse, nous avons dans un premier temps évalué l’association entre les données de sérologies anti-HSV et différents marqueurs de la MA en fonction de la présence de l’allèle APOE4, facteur de risque génétique de MA semblant moduler l’effet du virus sur le cerveau. En effet, la présence de facteurs de susceptibilité, notamment génétiques, permettrait d’expliquer pourquoi, malgré une séroprévalence d’approximativement 80%, certains sujets infectés restent « porteurs sains » tandis que d’autres développent la maladie. Dans les cohortes Trois Cités Bordeaux et AMI (Aging Multidisciplinary Investigation), nous avons ainsi mis en évidence que, parmi les sujets porteurs de l’allèle APOE4, les sujets infectés avaient 2 fois plus de risque de développer une MA par rapport aux non-infectés et 3 fois plus s’ils présentaient un taux d’IgG anti-HSV élevé (reflet possible de réactivations virales plus fréquentes au cours du temps) ; à l’inverse, aucune association n’était retrouvée chez les non-porteurs d’APOE4. Les sujets infectés avaient également plus d’altérations de la microstructure de la substance blanche au niveau du cingulum et du fornix para-hippocampiques que les sujets non infectés et, pour ceux ayant un taux d’IgG élevé, ils présentaient également un volume hippocampique plus faible. Paradoxalement, au sein de l’essai MAPT (Multidomain Alzheimer Preventive Trial), nous avons mis en évidence que, parmi les porteurs de l’allèle APOE4, les sujets infectés (et particulièrement ceux ayant un taux élevé d’IgG) avaient significativement moins de dépôts amyloïdes que les non-infectés tandis qu’aucune association n’était retrouvée chez les sujets non-porteurs d’APOE4. Ce résultat, bien qu’allant dans le sens inverse de celui attendu, pourrait potentiellement être expliqué par un biais de sélection des sujets inclus dans l’essai. Enfin, grâce aux données de 68 291 sujets âgés issus de l’Echantillon Généraliste des Bénéficiaires suivis entre 2009 et 2017, nous avons mis en évidence que la prise d’au moins un anti-herpétique à action systémique était associée à une diminution de 15% du risque de développer une MA. Malgré un nombre faible de participants avec une prise régulière durant le suivi, cette association pourrait refléter un effet protecteur du traitement, en particulier si l’on considère la possibilité d’un traitement plus régulier durant la période de vie précédant l’inclusion. Au total, si nos résultats semblent en faveur de l’implication du virus HSV-1 dans la MA, de nombreuses questions restent encore en suspens pour confirmer cette hypothèse et son potentiel en termes de préventionDespite many advances in the understanding of the mechanisms involved in Alzheimer's disease (AD), its precise etiology remains unknown. However, an increasing number of articles suggest that an involvement of the Herpes Simplex virus type 1 (HSV-1) could explain both the topographic and temporal sequences as well as the type of damage found in AD. Indeed, HSV-1 is a neurotropic virus found in the brains of elderly people and it has a particular tropism for the areas involved in AD. It is also able to spread from cell to cell. During life, HSV-1 remains latent in the body and is able to reactivate periodically. With advancing age, the decline of the immune system could allow more frequent and/or intense reactivations of the virus, potentially explaining the late and progressive onset of AD. In addition, the main pathological markers of AD (amyloid and tau pathologies, neuroinflammation) can be induced in vitro and in animal models by inoculation of the HSV-1 virus and the accumulation of the aβ peptide could be due to its involvement in antimicrobial defense. In this thesis, in order to test this hypothesis, we first evaluated the association between anti-HSV serologies and different markers of AD according to the presence of the APOE4 allele, a genetic risk factor for MA which may modulate the effect of the virus on the brain. Indeed, the presence of susceptibility factors, genetic or not, would explain why, despite a seroprevalence of approximately 80%, some infected subjects remain "healthy carriers" while others develop the disease. In the Trois Cités Bordeaux and the AMI (Aging Multidisciplinary Investigation) cohorts, we demonstrated that, among the APOE4 carriers, the infected subjects had 2 times the risk of developing AD than the non-infected and three times if they had a high level of anti-HSV IgG (possible reflection of more frequent viral reactivations over time); conversely, no association was found in APOE4 non-carriers. Infected subjects also had more alterations of the white matter microstructure in the parahippocampal cingulum and fornix than uninfected subjects, and if they had an elevated IgG levels, they also presented lower hippocampal volumes. Paradoxically, in the MAPT trial (Multidomain Alzheimer Preventive Trial), we demonstrated that, among APOE4 carriers, infected subjects (and particularly those with high IgG levels) had significantly less amyloid deposits than uninfected individuals while no association was found in APOE4 non carriers. This result, although going in the opposite direction to that expected, could potentially be explained by a selection bias of the subjects included in the trial. Then, using medico-administrative data from 68,291 elderly subjects monitored between 2009 and 2017, we demonstrated that taking at least one systemic anti-herpetic drug was associated with a 15% decrease in the risk of developing AD. Despite a low percentage of participants with regular intake during follow-up, this association could potentially reflect a protective effect of the treatment, in particular considering the possibility of more regular treatment during the period of life before inclusion. Overall, while our results seem in favor of the involvement of HSV-1 in AD, many questions still remain to confirm this hypothesis and its potential in terms of prevention
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Arone, Blanco Maria. "Effects of herpes simplex virus 1 (HSV-1) infection on nuclear amyloid aggregation." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-231319.
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Huntington’s disease (HD) and Spinocerebellar ataxia (SCA) are incurable neurodegenerative diseases that affect the central nervous system. Amyloids, highly organized protein aggregates, are a hallmark for many neurodegenerative diseases. The presence and accumulation of amyloids are toxic and constitute the major cause of neuron cell death. Both genetic and environmental factors contribute to the onset and progression of these diseases. However, despite intensive research, the underlying cause remains unclear. The role of viral infection as an environmental factor in the context of neurodegenerative diseases has not received much attention. The purpose of this study is to investigate the effects of Herpes Simplex Virus 1 (HSV-1) infection on nuclear amyloid aggregation in model cell lines of HD and SCA. The research process consists mainly of laboratory work which involved the use of several molecular techniques used in the field of biotechnology. The work comprises cultivating cells, infecting cells with HSV-1, Fluorescence microscopy, Western Blot and isolation and detection of amyloids. Western Blot is used for the analysis of specific proteins associated with protein aggregation in HD and SCA. The techniques used for detecting amyloids are Dot Blot and Antibody-staining of amyloids in cells. The results from Western Blot showed that aggregates changed in the presence of the virus. This pattern is observed for both HD and SCA1 cell lines. A big effort is done in this study to optimize Dot Blot as it is method that could be applied in every lab. Normalization of samples proved to be the most challenging part with Dot Blot. No definitive conclusions can be drawn from the Dot Blot results as reproducibility and sensitivity were lacking. This work addresses some of the difficulties encountered when working with detection of amyloids especially Dot Blot. Antibody-staining of amyloids showed that amyloids were formed in the presence of virus in comparison to non-infected. To conclude, aggregates changed, and amyloids were formed in the presence of virus. These results point to the fact that HSV-1 infection could be involved in the process of nuclear amyloid aggregation. The data presented in this thesis will need further investigation and characterization to identify the precise role of viral-induced amyloid formation in HD and SCA patient cells.Huntingtons sjukdom (HD) och Spinocerebellära ataxier (SCA) är obotliga neurodegenerativa sjukdomar som påverkar det centrala nervsystemet. Amyloid, proteinaggregat som har en viss konformation är ett kännemärke för många neurodegenerativa sjukdomar. Ackumulering av dessa amyloider är toxiskt och är den främsta orsaken till att nervceller dör. Både genetiska faktorer och miljöfaktorer bidrar till uppkomsten och progressionen av dessa sjukdomar. Trots intensiv forskning är den bakomliggande orsaken emellertid fortfarande oklar. Virusinfektion som en potentiell miljöfaktor har i detta sammanhang inte fått mycket uppmärksamhet. Syftet med denna studie är att undersöka effekterna av Herpes Simplex Virus 1 (HSV-1) infektion på amyloid aggregering i modellcellinjer av HD och SCA. Forskningsarbetet bestod i huvudsakligen av experimentellt arbete med hjälp av flera molekylära tekniker inom bioteknikområdet som cell odling, infektering av celler med HSV-1, fluorescensmikroskopi, Western Blot och isolering och detektion av amyloider. Western Blot användes for att analysera specifika proteiner associerade med protein aggregering i HD och SCA. Amyloider detekterades med Dot Blot och med antikroppar specifika för amyloider. Resultat från Western Blot visade att amyloiderna förändras i virusinfekterade celler. Detta mönster observerades i både HD and SCA1 cellinjer. En stor bemöda görs i denna studie för att optimera Dot Blot eftersom det är en metod som kan användas i alla laboratorier. Normalisering visade sig vara det svåraste med detektion av amyloider. Inga definitiva slutsatser kan dras från dessa experiment, eftersom reproducerbarhet och känslighet var bristande. Detta arbete tar upp några av de svårigheter som uppstod vid arbetande med detektion av amyloider speciellt Dot Blot. Detektion av amyloider med antikropp visade att amyloider bildades till stor utsträckning i infekterade cellinjer i jämförelse med icke-infekterade. Sammanfattningsvis, amyloider förändrades och amyloider bildades i närvaro av virus. Dessa resultat indikerar på att HSV-1 infektion skulle kunna vara involverad i processen av amyloid aggregering. De presenterade uppgifter i detta examensarbete är preliminära och behöver följas upp med ytterligare studier för att identifiera virusens exakta roll i amyloid bildning i HD och SCA patient celler.
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Lee, Sung Seok. "The role of autonomic neurons in the pathegenesis of herpes simplex virus infection." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/64503.
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Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are major human pathogens. HSV establishes latency in the nervous system and reactivates to cause recurrent disease, resulting in transmission of progeny virions to naïve individuals. Though HSV-1 and HSV-2 share similar structure and genes, they have distinctive recurrence profiles. Generally, HSV-1 reactivation is associated with disease 'above the waist' and HSV-2 reactivation is associated with disease 'below the waist'. This phenomenon was described decades ago but still remains unexplained.
The mechanism of HSV latent infection in the peripheral nervous system (PNS) has been extensively investigated, especially with in sensory neurons. Another component of the peripheral nervous system (PNS), autonomic neurons, were also known to be infected with HSV productively and latently, but largely ignored because of the assumption that there is no difference in the pathogenesis of HSV in the neurons and that both HSV-1 and HSV-2 behave in the same way in different types of neurons.
However, autonomic neurons differ in physiological function compared to sensory neurons. Activation factors of autonomic neurons, such as emotional stress, trauma and hormonal fluctuation, are also known HSV reactivation triggering factors. Therefore, I hypothesized that autonomic neurons innervating the site of HSV infection are responsible the different reactivation frequencies of HSV-1 and HSV-2 after peripheral invasion.
In this report, the role of autonomic neurons in HSV pathogenesis were examined using the female guinea pig reactivation model. Major findings of this report are that 1) parasympathetic ganglia innervating the ocular region support latent infection of HSV-1 selectively, thus contributing the more frequent HSV-1 reactivation, 2) mixed autonomic ganglia in the genital area support HSV-2 latent infection selectively, and 3) sympathetic neurons in the genital region supported productive and latent infection of HSV-1 and HSV-2 differently.
All of the results in this report indicate that autonomic neurons play a distinctive role in HSV pathogenesis compared to the sensory neurons and are responsible for the different reactivation frequencies of HSV-1 and HSV-2. This report raises the importance of autonomic neurons in HSV pathogenesis and challenges the paradigm of HSV pathogenesis.Ph. D.
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Obasi, Angela I. N. "The epidemiology of herpes simplex virus type 2 infection in Mwanza region, Tanzania." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536824.
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TARTIERE, LAFONT CHRISTINE. "Les meningo-encephalites infectieuses aigues a liquide clair de l'adulte : d'apres une etude retrospective de 36 cas observes au chru de clermont-ferrand, de janvier 1989 a septembre 1992." Clermont-Ferrand 1, 1993. http://www.theses.fr/1993CLF1M003.
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Van, Buren Lauren Kay. "HSV-1 Infection of C3H Central Nervous System Cell Lines." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1189746668.
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Kumaraswamy, Guttalu K. "INNATE AND ADAPTIVE HOST RESPONSE DURING THE INITIAL PHASE OF HERPES SIMPLEX VIRUS ENCEPHALITIS IN THE NEONATAL MOUSE." Kent State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=kent1168650862.
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Speck, Peter Gerald. "Analysis of establishment of latent infection with a virulent strain of herpes simplex virus type 1 /." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phs7415.pdf.
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Mitterreiter, Johanna Gracia [Verfasser]. "Virus and Host Factors Involved in Herpes Simplex Virus Infection of the Human Nervous System / Johanna Gracia Mitterreiter." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2017. http://d-nb.info/1150336951/34.
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Bonnet, Catherine. "Surinfection cutanée à Herpes simplex virus (HSV) dans un service de brûlés : à propos de 9 observations." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2M034.
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Ives, Angela M. "Stress hormones epinephrine and corticosterone modulate herpes simplex virus 1 and 2 productive infection and reactivation primarily in sympathetic, not sensory, neurons." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/78862.
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Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect and establish latency in peripheral neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is associated with exacerbation of clinical symptoms and induction of recurrences in humans and animal models. The viruses preferentially replicate and establish latency in different subtypes of sensory neurons, as well as in neurons of the autonomic nervous system that are highly responsive to stress hormones. To determine if stress-related hormones modulate productive and latent HSV-1 and HSV-2 infection within sensory and autonomic neurons, we analyzed viral DNA after treatment of primary adult murine neuronal cultures with the stress hormones epinephrine and corticosterone. Both sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) neurons expressed adrenergic receptors and glucocorticoid receptor. In productively infected neuronal cultures, epinephrine treatment significantly increased HSV-1 DNA replication and production of viral progeny in SCG neurons, but no significant differences were found in TG neurons. In contrast, corticosterone significantly decreased HSV-2 DNA replication and production of viral progeny in SCG neurons, but not in TG neurons. In quiescently infected neuronal cultures, epinephrine and corticosterone significantly increased HSV-1 reactivation from sympathetic SCG neurons, but not sensory TG neurons. In contrast, corticosterone increased HSV-2 reactivation from both SCG and TG neurons, but epinephrine had no effect. Adrenergic or epinephrine-induced reactivation of HSV-1 in SCG neurons involved activation of several adrenergic receptors, the cyclic AMP response element binding protein (CREB), the transcription factor β-catenin, and the c-Jun N-terminal kinase (JNK). Corticosterone-induced reactivation of HSV-1 in SCG neurons required activation of glucocorticoid receptor (GCR) and transcription factors CREB and JNK. In contrast, corticosterone-induced reactivation of HSV-2 in TG and SCG neurons could utilize either the GCR or mineralocorticoid receptor (MCR) and most likely involves the chromatin remodeling properties of those receptors. Thus, stress-related hormones, epinephrine and corticosterone, selectively modulate productive and quiescent HSV-1 and HSV-2 infections primarily in sympathetic, but not sensory, neurons through different mechanisms. These results have implications for describing a mechanism by which stress-induced reactivation may occur in humans.Ph. D.
Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) are major human pathogens, which establish latency in neurons of the peripheral nervous system and reactivate to cause recurrent disease in humans. Physiological stress, which includes the secretion of the stress hormones epinephrine and cortisol, has been associated with increases in severity of clinical signs and increased recurrent disease in humans and animal models of herpetic disease. The mechanism by which physiological stress induces HSV reactivation has been assumed to be through suppression of the immune system. In addition, it has been assumed that sensory neurons harboring latent HSV are the primary source of reactivating virus for recurrent HSV disease. However, my dissertation provides evidence that the stress hormones epinephrine and corticosterone (the rodent equivalent of cortisol) can act on peripheral neurons in which the virus is latent, rather than through immune system suppression. In addition, my dissertation provides evidence that the autonomic nervous system, which modulates the physiological stress response, is an important source of reactivating virus to cause recurrent disease. The molecular pathway by which epinephrine and corticosterone induce HSV reactivation in primary adult murine neurons involves specific receptors, transcription factors, and protein kinases that could potentially be targeted in humans for inhibition of HSV reactivation and prevention of herpetic recurrent disease.
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Bishop, S. A. "Herpes simplex virus infection and damage in the central nervous system : The role of the immune response." Thesis, University of Bristol, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376607.
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Champion, Patrick D. "An analysis of Fourier transform infrared spectroscopy data to predict herpes simplex virus 1 infection." Atlanta, Ga. : Georgia State University, 2008. http://digitalarchive.gsu.edu/math_theses/62/.
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Thesis (M.S.)--Georgia State University, 2008.Title from title page (Digital Archive@GSU, viewed July 29, 2010) Yu-Sheng Hsu, committee chair; Gary Hastings, Jun Han, committee members. Includes bibliographical references (p. 41).
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Weinstein, Debra Lynn. "Major histocompatibility complex antigens in the rat CNS following herpes simplex virus type 1 infection." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/27681.
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The present study was designed to determine major histocompatibility complex (MHC) expression in the rat CNS following a viral infection. Male Wistar rats were anesthetized with ether and the right cornea was repeatedly scratched with a 23.5 gage needle. A 30 microliter drop of Herpes Simplex Virus Type 1 (HSV1) (PFU 33,000/mL) was placed on the scarified cornea. Animals were sacrificed 3, 6, 8, 10, 12, and 30 days following infection. Following decapitation, the brains were removed and placed in Zamboni fixative for immersion fixation. Monoclonal antibodies against rat MHC class I/class II antigens and HSV1 as well as polyclonal glial fibrillary acidic protein (GFAP) were used in both single and double staining procedures.
Neurons staining positively for HSV1 were observed in the ipsilateral principal sensory nucleus of the fifth nerve. Fifth nerve axons were also positive. Additional infected areas included midline brainstem structures, hypothalamus, thalamus, cerebellum and diffuse cortical regions. Infection became increasingly pronounced through day 10. Two animals who recovered from the viral encephalitis were sacrificed on days 12 and 30; they demonstrated much less positive HSV1 staining. In the infected animals, serial sections revealed both class I and class II positive staining of non-neuronal cells in brain areas which were also positive for HSV1. Endothelial cells and cells with microglia-like morphology were positively stained for class I and expression increased through day 10. The class II positive cells had the morphology of leukocytes and microglia-like cells with increased expression occurring through days 8 and 10 throughout the brain. In serial sections, dense areas of class II positive microglia-like cells were located in the same areas as HSV1 positive clusters. MHC expression in the day 12 animal was quite pronounced with decreasing levels observed at 30 days. Tissue doubly stained for class II and GFAP demonstrated no overlap among positively stained cells suggesting that astrocytes were not expressing MHC glycoproteins. Astrocytes did, however, show morphological changes consistent with an acute CNS infection.
Microglia are an endogenous component of the CNS which may be phagocytotic, but the full range of functions which microglia possess is still unclear. The results of the present study indicate that MHC expression occurs in the CNS as early as 6 days following viral infection with increased expression through day 10. Continued high levels of class II expression at 12 days, following substantial active virus clearing, strongly suggest ongoing immune system activity which appears to be present at least as long as 30 days post-infection. Peripherally, MHC expression is involved in the induction of an immune response, suggesting that the rat brain is capable of mounting an immune response to viral infection. Microglia expressing class II antigens may possess the ability to present antigen to T cells and thereby initiate an immune response within the CNS. The present study suggests that MHC antigens may play an active role in viral clearance from the CNS.Medicine, Faculty of
Graduate
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Goldthorpe, Sian Elinor. "Effects of guanosine analogues on herpes simplex virus type 1 infection in cell culture and in a murine model of herpes encephalitis." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386689.
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Mardelle, Vincent. "Infection cutanée à herpès simplex virus chez les brûlés : étude prospective sur un an dans le service de grands brûlés de Bordeaux." Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M033.
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Tscharke, David C. "Transcriptional analysis of the role of CD8+ T lymphocytes in acute neural herpes simplex virus infection /." Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09pht877.pdf.
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Hsu, Wei-Li. "Herpes simplex virus type-1 infection and ND10 characteristics in cultured fibroblast and neuronal-like cells." Thesis, University of Glasgow, 2002. http://theses.gla.ac.uk/3962/.
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Nuclear domain 10 (ND10) are punctate subnuclear structures that exist in most cell types. It has been suggested that ND10 structures serve as the site for initial viral genome deposition and some viral proteins, such as the ICP0 protein of HSV-1, have been shown to colocalise to, and subsequently induce the degradation of, proteins present in ND10. However the exact function of ND10 during HSV-1 infection is still unknown. In this study, the potential role of ND10 in HSV-1 infection was investigated by assessing the efficiency of viral IE and E gene expression or viral replication in cultured cells in which the expression of ND10 proteins was increased by IFN treatment or transient transfection methods. Furthermore, this study objective was also approached by using a human neuron precursor cell line (NT2) that naturally lacks one ND10 component, Sp100, and was found to have abnormal ND10 characteristics. The infectivity of HSV-1 in NT2 and differentiated hNT neuronal-like cells was investigated and the function of ICP0 in these cells was studied in more detail. Treatment with IFN- increased the number and size of ND10, whereas heat-stress caused dispersal of ND10 proteins, although this did not appear to affect HSV-1 infection. Pre-treatment with IFN- slightly inhibited HSV-1 gene expression, however it was not clear whether this effect was mediated by the ND10 proteins that are up-regulated by IFN. Examination of cells transiently transfected with plasmids expressing ND10 proteins (either PML, Sp100, SUMO-1 or Ubc9) demonstrated that the expression of viral IE and L genes was not affected by high expression levels of ND10 proteins. However, decreased viral gene expression was observed at an early time of infection in cells co-transfected with three plasmids expressing PML, Sp100, and Ubc9 or with four plasmids expressing PML, Sp100, Ubc9, and SUMO-1. Notably, in cells transfected with multiple plasmids, the exogenous ND10 proteins were sequestered in ND10 to a greater extent than in cells singly transfected. These observations suggested that over-expression of ND10 proteins, properly located in ND10, confers a marginal resistance to HSV-1 infection at an early time of infection, but this effect was less clear at later times of infection.
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Lewis, David John. "Biological and clinical significance of chronic herpes virus infection in patients undergoing treatment for myeloid malignancies." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5832/.
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Cytomegalovirus (CMV) is a β-herpes virus that infects the majority of the world’s population. Tyrosine kinase inhibitors (in particular imatinib, dasatinib and nilotinib) have been successfully used in the treatment of chronic myeloid leukaemia, as they target the \(Abl\) kinase, which is constitutively activated in the disease. Although thought of as targeted therapies, they have significant “off target” effects including inhibition of \(Src\) family kinases important in T cell receptor mediated activation. I demonstrated that CMV infection is associated with significant alterations in the immune repertoire in imatinib-treated patients; in particular with expansions of differentiated CD8 T cells and Vδ1 γδ T cells. Furthermore, dasatinib treatment is associated with evidence of subclinical CMV reactivation and marked expansions of terminally differentiated CD8 T cells and Vδ1 γδ T cells. These atypical Vδ1 γδ T cells have activity against CMV infected fibroblasts, and sequencing of their TCRs demonstrated remarkable oligoclonality suggestive of antigen driven proliferation. In a second group of patients that underwent reduced intensity allogeneic stem cell transplant for myeloid malignancies, CMV seropositivity of patient or donor is associated with increased lymphocyte counts at 3 months post transpant, particularly of CD8 and Vδ1 γδ T cell subsets. Survival analysis of these patients revealed that CMV seropositivity is associated with improved overall survival, due to a decreased relapse risk.
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Binks, Alexander William David. "The role of immunogenic cell death in oncolytic herpes simplex virus-1 infection of cancer cells." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30718/.
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Patients living with many cancers, including ovarian cancer (OC), often suffer from a lack of adequate treatment options. In the case of OC, primary debulking surgery followed by platinum and paclitaxel chemotherapy has led to a vast improvement in patient survival over the past few decades, however, rates of drug-resistant recurrence remain high. Research into new, experimental treatment options is therefore warranted for OC and other cancers. Oncolytic viruses (OVs) are replication-competent viruses that can selectively infect and destroy cancerous cell types, while leaving healthy cells unharmed. OVs do this by exploiting differences between cancer and normal cell phenotypes. Herpes simplex virus (HSV)-1, strain 1716 is one example of this type of virus that has shown selectivity for cancer cells in previous preclinical studies, as well as high levels of safety in humans. One prominent area of current OV study seeks to investigate the ability of OVs to induce immunogenic cell death (ICD) – this term describes multiple modes of programmed death pathways that culminate in release of proimmunogenic factors, which facilitate a modification of the host immune system. Two of the most prominent of these pathways are necroptosis and immunogenic apoptosis (IA). Here, I show that while many OV cell lines express the necessary components for necroptosis, they are unable to undergo classical necroptotic death (induced by TSZ). Despite this, HSV-1716 can infect and kill a range of OC lines successfully. I showed that HSV-1716-induced cell death displays two markers of IA yet does not seem to rely solely on apoptosis to kill cells. In addition, it appears not to rely on any components of the necrosome in order to kill cells, even in cells that are competent to typical necroptosis. However, when RIPK3 is overexpressed in HeLa cells, virus-induced cell death increases, as do markers of both necroptosis and IA. To investigate the role of ICP6 in HSV-1716-induced ICD, viral and cell mutants were made possessing various forms of the protein. Full-length ICP6 protein expressed in cell lines had the effect of blocking cellular response to TSZ, but constructs lacking a region known as the RHIM did not. A functionally similar mutation was produced within the RHIM of live HSV-1716 using CRISPR/Cas9 technology, which was shown to have the effect of disrupting ICP6/RIPK3 binding – thought to be the determinant of necroptotic cell death. Despite this, no changes in cell death signalling could be determined between the viruses at all. Interestingly, when cells were infected in combination with TNF-α, or TNF-α in addition to SMAC mimetic, the RHIM-modified virus produced significantly more death than HSV-1716. This suggests that while loss of RIPK3 inhibition is not sufficient to lead to increased necrosis alone, cells infected with this virus are more sensitive to further necrosis induction. This finding may prove to have great utility for producing the next generation of oncolytic viral therapeutics which can induce greater levels of proimmunogenic cell death. From this we can conclude that HSV-1716 is capable of inducing IA in OC cells. Death is not dependent on necroptosis, however additional RIPK3 seems to sensitise cells to death by other means. Cellular binding of viral ICP6 and RIPK3 can be disrupted by modification of the RHIM, although this change has no bearing on ICD signalling alone but can sensitise cells to TNF-α-induced death.
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ADAM, CATHERINE. "Prevention par l'aciclovir per os des infections a virus herpes simplex hominis au cours des transplantations medullaires de l'enfant." Nancy 1, 1989. http://www.theses.fr/1989NAN11055.
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Bryant, Helen Elizabeth. "Analysis of cellular and viral proteins that interact with the IE63 protein of herpes simplex virus type 1." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312135.
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Chatterjee, Koushik. "A study of host genetic determinants of human papillomavirus (HPV) infection, cervical cancer and herpes simplex virus type-2 (HSV-2) infection." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/3160.
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Svensson, Alexandra. "Immune regulation of herpes simplex virus type 2 infection : special emphasis on the transcription Factor T-bet /." Göteborg : Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, Göteborg University, 2006. http://hdl.handle.net/2077/852.
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Kather, Angela. "Pro- and antiapoptotic events in Herpes simplex virus type 1 (HSV-1) infection of immature dendritic cells." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16464.
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Herpes simplex virus Typ 1 (HSV-1) ist ein humanpathogenes Virus der Familie Herpesviridae. Für eine erfolgreiche Virusreplikation besitzt HSV-1 mehrere Gene, die in den meisten infizierten Zelltypen Apoptose verhindern. Im Gegensatz dazu führt die HSV-1 Infektion eines zentralen Zelltyps des Immunsystems, den unreifen dendritischen Zellen (iDCs), zu Apoptose. Dies könnte ein Aspekt der HSV-1 Immunevasion sein. Bisher waren die Ursachen der Apoptose von HSV-1 infizierten iDCs unzureichend aufgeklärt. Es wurde jedoch gezeigt, dass das antiapoptotische zelluläre Protein c-FLIP in HSV-1 infizierten iDCs reduziert ist. In dieser Arbeit wurde die c-FLIP Menge in iDCs erstmalig mit Hilfe von RNA Interferenz erfolgreich reduziert. Dies bestätigte die Bedeutung von c-FLIP für die Lebensfähigkeit von iDCs. Folglich könnte auch die Reduktion der c-FLIP Menge nach HSV-1 Infektion iDCs für Apoptose empfindlich machen. Die HSV-1 induzierte c-FLIP Reduktion erfolgte in späten Stadien der Infektion, abhängig von der ordnungsgemäßen Expression viraler „early“ und „leaky late“ Gene. Sie fand nicht auf RNA Ebene statt und war unabhängig vom Proteasom und der Bindung an den „death inducing signaling complex“. Stattdessen wurde c-FLIP wahrscheinlich von einer viralen oder zellulären Protease abgebaut. In dieser Arbeit wurde erstmals gezeigt, dass zusätzlich zu Veränderungen im zellulären Apoptosesignalnetzwerk der Mangel an einem antiapoptotischen viralen Faktor zur Apoptose von HSV-1 infizierten iDCs beiträgt. Eine Microarray Analyse der HSV-1 Genexpression ergab, dass HSV-1 Latenz-assoziierte Transkripte (LATs) in apoptotischen iDCs signifikant geringer exprimiert waren als in nicht-apoptotischen epithelialen Zellen. LATs besitzen in Neuronen und epithelialen Zellen eine antiapoptotische Aktivität. Diese könnte den Mangel an c-FLIP kompensieren. Übereinstimmend mit dieser Hypothese induzierte eine HSV-1 LAT-Deletionsmutante mehr Apoptose in iDCs im Vergleich zum Wildtyp-Virus.Herpes simplex virus type 1 (HSV-1) is a human pathogen which belongs to the family Herpesviridae. HSV-1 encodes several genes, which serve to efficiently prevent apoptosis in most infected cell types, thereby ensuring successful virus replication. In contrast, HSV-1 infection of one central cell type of the immune system, immature dendritic cells (iDCs), results in apoptosis. This could be one aspect of HSV-1 immunevasion. So far, the mechanisms underlying apoptosis of HSV-1 infected iDCs were poorly defined. However, it has been shown that the antiapoptotic cellular protein c-FLIP is reduced in HSV-1 infected iDCs. In this work, the amount of c-FLIP was for the first time successfully reduced in iDCs by RNA interference. This confirmed the importance of c-FLIP for viability of iDCs. Therefore, it is likely that c-FLIP reduction after HSV-1 infection also sensitizes iDCs to apoptosis. HSV-1 induced c-FLIP reduction occurred at late stages of infection and was dependent on proper expression of early and leaky late virus genes. Furthermore, it was not operative at the RNA level and was independent from the proteasome and binding to the death inducing signaling complex. Rather, c-FLIP was presumably degraded by a viral or cellular protease. In this work it was shown for the first time, that in addition to changes in the cellular apoptosis signaling network, the lack of one antiapoptotic viral factor contributes to apoptosis of HSV-1 infected iDCs. HSV-1 latency-associated transcripts (LATs) were significantly lower expressed in apoptotic iDCs compared to non-apoptotic epithelial cells, determined by microarray analysis of HSV-1 gene expression. It is known that in neurons and epithelial cells, LATs possess a potent antiapoptotic activity. This could compensate the lack of c-FLIP. Consistent with this hypothesis, a LAT deletion mutant of HSV-1 induced more apoptosis in iDCs compared to the respective wild type virus.
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Teo, Su Hui Catherine. "Spatiotemporal resolution of global protein synthesis during herpes simplex virus infection using bioorthogonal precursors and click chemistry." Thesis, Imperial College London, 2018. http://hdl.handle.net/10044/1/63934.
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Herpes simplex virus (HSV) modulates the host cell’s proteome and transcriptome during infection to fulfil the needs of the virus for productive replication and transmission. Using bioorthogonal precursors and click chemistry, I have examined spatiotemporal aspects of global protein synthesis during single step replication and cell-to-cell transmission with results revealing new insights into the complex spatial interplay between translational control processes, protein localisation and transcription during HSV infection. For the first time, translational suppression and recovery is visualised at the single cell level, reflecting a very early biphasic switch in translational control. The biphasic switch is dependent on the RNase activity of HSV virion host shutoff protein (vhs), and vhs also mediates eIF4H nuclear translocation coupled to the initial suppression. During translational recovery, my results also show rapid accumulation of newly synthesised proteins in novel subnuclear domains termed newly synthesised protein domains (NPDs). ICP22 is specifically required for NPD formation and shows selective recruitment to these domains. Additionally, a host protein, SSRP1, is also displaced from its normal localisation in the nucleolus and selectively recruited to NPDs very early in infection, dependent on ICP22 expression. Furthermore, spatial analysis of newly transcribed RNA also reveals that early after infection transcripts accumulate in irregular structures termed RNA islands which form distinct populations. While a fraction of RNA islands localises juxtaposed with a subpopulation of NPDs, the majority of this newly synthesised RNA shows precise colocalisation in distinct domains which also recruits a cellular RNA helicase, p68. These later RNA domains adjoin foci containing the immediate-early transcriptional regulator ICP4 in a specifically organised manner. In addition to profound qualitative changes observed during translational recovery, quantitative proteomics and identification of the newly synthesised nuclear proteome using HPG pulsed-SILAC with LC- MS/MS indicates coordinated mobilisation of distinct cellular pathways, in particular eIF2 signalling pathway and RNA post-transcriptional modification. These results reveal new features of protein metabolism during infection, and involvement of ICP22 in newly synthesised protein processing pathways.
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Leoni, Valerio <1985>. "Role of αvβ3 – Integrin and TLR2 in the innate response to Herpes Simplex Virus infection and Delivery of retargeted oncolytic Herpes Simplex via carrier cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6464/.
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In the first part of my thesis I studied the mechanism of initiation of the innate response to HSV-1. Innate immune response is the first line of defense set up by the cell to counteract pathogens infection and it is elicited by the activation of a number of membrane or intracellular receptors and sensors, collectively indicated as PRRs, Patter Recognition Receptors. We reported that the HSV pathogen-associated molecular patterns (PAMP) that activate Toll-like receptor 2 (TLR2) and lead to the initiation of innate response are the virion glycoproteins gH/gL and gB, which constitute the conserved fusion core apparatus across the Herpesvirus. Specifically gH/gL is sufficient to initiate a signaling cascade which leads to NF-κB activation. Then, by gain and loss-of-function approaches, we found that αvβ3-integrin is a sensor of and plays a crucial role in the innate defense against HSV-1. We showed that αvβ3-integrin signals through a pathway that concurs with TLR2, affects activation/induction of interferons type 1, NF-κB, and a polarized set of cytokines and receptors. Thus, we demonstrated that gH/gL is sufficient to induce IFN1 and NF-κB via this pathway. From these data, we proposed that αvβ3-integrin is considered a class of non-TLR pattern recognition receptors. In the second part of my thesis I studied the capacity of human mesenchymal stromal cells isolated by fetal membranes (FM-hMSCs) to be used as carrier cells for the delivery of retargeted R-LM249 virus. The use of systemically administrated carrier cells to deliver oncolytic viruses to tumoral targets is a promising strategy in oncolytic virotherapy. We observed that FM-hMSCs can be infected by R-LM249 and we optimized the infection condition; then we demonstrate that stromal cells sustain the replication of retargeted R-LM249 and spread it to target tumoral cells. From these preliminary data FM-hMSCs resulted suitable to be used as carrier cells
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Woolard, Stacie N. "The Multifaceted Contribution of Natural Killer Cells During Herpes Simplex Type-1 Viral Infection." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etd/1672.
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Natural killer (NK) cells are non-specific killer cells of the innate immune system that eliminate target cells based on discrimination between self and non-self. Activation is carefully regulated through integration of signals received through both activating and inhibitory receptors. During the course of a herpes simplex virus type-1 (HSV-1) infection, NK cells can influence host susceptibility to infection with severe infections occurring in individuals with genetic defects in the NK cell response. In response to HSV infection, NK cells are recruited to the inflammatory tissue where ensuing reciprocal interactions with accessory cells and proinflammatory cytokines induce NK cell activation, cytolytic activity, and cytokine production, contributing to innate immune response and ultimately influencing the adaptive immune response. The objective of this study was to elucidate the multiple roles of NK cells during the numerous steps in anti-HSV immune induction. Accordingly, we have demonstrated that NK cells are novel helpers that assist and influence an anti-HSV immune response via the secretion of cytokines that enhance HSV-specific CD8+ T cell effector function and cytokine production. Taken together, data from this study presented the critical importance of NK cells in mounting an essential and efficient anti-HSV immunity. The key findings of our study were: 1. In the absence of NK cells, dendritic cells have decreased capacity to prime HSV-specific T cells. 2. HSV infected NK cells can be directly activated via toll-like receptor (TLR) in a MyD88-dependent mechanism; however, interaction with HSV infected dendritic cells yields optimal NK cell activation and function (CD69 and IFNγ). 3. TRAIL-expressing NK cells eliminate antigen-bearing immature dermal DCs (CD11c+CD8α-DR5+), that migrate to draining lymphoid organs, to facilitate antigen transfer to lymphoid resident CD8α+ DC for T cell cross priming. 4. 'Helpless' CD8+ T cell function, generated in the absence of CD4+ T cells, can be partially restored to wild-type levels by NK cell supplementation. 5. Treatment of NK cells with anti-CD69 antibody results in a heightened NK activated state and augments the adaptive immune response, without increasing NK cell numbers. These findings may contribute to the potential revelation of avenues to manipulate NK cells for anti-viral therapies.
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Thapa, Manoj. "Chemokines and chemokine receptors that mediate immune defense to genital herpes simplex virus type 2 (HSV-2) infection." Oklahoma City : [s.n.], 2008.
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Alandijany, Thamir Abdulaziz A. "Distinct temporal regulation of intrinsic and innate intracellular immunity to Herpes Simplex Virus type 1 (HSV-1) infection." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30662/.
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Intrinsic and innate immunity play pivotal roles in limiting the replication of invading viral pathogens. Intrinsic immunity is constitutive and mediated by pre-existing host cell restriction factors (e.g., promyelocytic leukemia-nuclear body (PML-NB) constituent proteins) which directly confer antiviral properties. On the other hand, innate immunity is inducible and upregulated in response to infection. Pattern recognition receptors (PRRs) (e.g., interferon gamma inducible protein 16 (IFI16)) sense pathogen-associated molecular patterns (PAMPs) and induce downstream signaling cascades leading to the induction of Interferon-stimulated gene (ISG) products that confer antiviral properties. These two arms of immunity represent the first line of intracellular defense to HSV-1 infection. Indeed, rapid recruitment of intrinsic and innate immune factors to viral DNA (vDNA) has a significant bearing on the outcome of infection. However, the spatial and temporal regulation of this recruitment remains poorly defined due to the technical challenges associated with vDNA detection at multiplicities of infection (MOI) that do not saturate intrinsic host factors. Utilizing 5-Ethynyl-2’-deoxyuridine (EdU) labeling of HSV-1 DNA in combination with click chemistry, we directly visualized input viral genomes under low MOI conditions (MOI of ≤ 3 PFU/cell) at 30-90 minutes post-addition of virus (mpi). This protocol is sensitive, specific, and compatible with indirect immunofluorescence (IF) staining protocols, providing a valuable assay to investigate the temporal recruitment of immune regulators to infecting vDNA. Upon entry of vDNA into the nucleus, PML-NB associated restriction factors (e.g., PML, SP100, and Daxx) were rapidly recruited to infecting viral genome foci. This process occurred in a PML-dependent manner and led to genome entrapment and silencing within PML-NBs. Interestingly, genome entrapment was observed during both wild-type (WT) and ICP0-null mutant (ΔICP0) HSV-1 infection. During WT HSV-1 infection, ICP0 induced PML degradation and the dispersal of PML-NB restriction factors, highlighting the importance of ICP0 to release viral genomes entrapped within PML-NBs to stimulate the onset of lytic HSV-1 replication. During ΔICP0 HSV-1 infection, vDNA remained stably entrapped within PML-NBs leading to a repression in viral gene expression and a restriction in plaque formation. Importantly, IFI16 was not stably recruited to vDNA entrapped within PML-NBs, and ISG expression was not induced under low MOI conditions that do not saturate PML-NB intrinsic host defenses. These data demonstrate that vDNA entry into the nucleus alone is not sufficient to stimulate the induction of innate immunity. Saturation of intrinsic host defenses under high MOI conditions stimulated the stable recruitment of IFI16 to infecting viral genomes, and induced ISG expression in a PML-, IFI16-, and Janus-associated kinase (JAK)-dependent manner. The induction of this innate immune response was dependent on the onset of vDNA replication, as treatment of the infected cell monolayers with phosphonoacetic acid (PAA), a vDNA polymerase inhibitor, inhibited ISG induction in a dose-dependent manner. Unlike PML depletion, inhibition of JAK signaling failed to relieve the plaque formation defect of ΔICP0 HSV-1, but instead significantly enhanced virus yields. Collectively, these data, for the first time, demonstrate a temporal and sequential induction of intrinsic and innate immunity during HSV-1 infection. Intrinsic immunity is induced within minutes of nuclear infection to restrict the initiation of viral gene transcription and the onset of lytic replication. Escape from this intrinsic repression and initiation of vDNA replication, which takes several hours, triggers the induction of innate immunity. ISG products establish an antiviral state within infected and neighboring uninfected cells to constrict viral propagation and limit the spread of infection. We identify dual roles for PML in the regulation of intrinsic and innate immunity to HSV-1 infection. However, these host defenses are counteracted by the viral ubiquitin ligase ICP0, which targets PML for degradation to promote vDNA release from PML-NBs in order to evade intrinsic viral genome silencing from the onset of nuclear infection.
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Laurent, Anne-Marie. "Régulation traductionnelle de l'expression génique cellulaire et virale après infection par le virus herpes simplex de type 1." Lyon 1, 1998. http://www.theses.fr/1998LYO1T043.
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Pedraza-Ordóñez, Francisco Javier [UNESP]. "Resposta celular no encéfalo de coelhos experimentalmente inoculados com herpesvírus bovino 5 (BoHV-5)." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/104612.
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O BoHV-5 é um alfa herpesvírus neurovirulento, que causa meningoencefalite fatal em bezerros. A morbidade é baixa contrastando com uma alta mortalidade, embora alguns animais possam-se recuperar. Varias pesquisas tem sido desenvolvidas para determinar a patogênese deste tipo de doença. No presente trabalho coelhos experimentalmente infectados com o Herpesvírus Bovino 5 (BoHV-5) foram submetidos a análise imuno-histoquímica e molecular, mediante a real time PCR, para descrever a resposta inflamatória em seis diferentes regiões do seu encéfalo. Todos os animais mostraram sinais neurológicos severos e foram eutanasiados vinte dias após a infecção inicial. Microscopicamente foi descrita uma meningoencefalite não supurativa, caracterizada por meningite, manguitos perivasculares mononucleares e malacia, mas não foram observados corpúsculos de inclusão viral. Os linfócitos T constituíram uma alta percentagem das células mononucleares envolvidas na neuroinflamação. Não foram encontradas diferenças significativas na resposta astrocitária quando comparados o grupo experimental e o grupo controle (p > 0,05). A quantificação viral pela qPCR permitiu achar partículas virais em todas as regiões encefálicas, de todos os animais do grupo experimental, sendo diretamente proporcional a quantidade de vírus e a visualização de lesões histológicas no encéfalo dos coelhos, assim como a imunodetecção do BoHV-5 pela imunohistoquímica. É possível suspeitar de um forte envolvimento do sistema imunitário do hospedeiro que fez a maioria dos animais reagir de maneira diferente ante a mesma quantidade do inóculo viral ministrado
The BoHV-5 is a neurovirulent alpha herpesvirus, which causes fatal meningoencephalitis in calves. The morbidity is low in contrast with a high mortality, although some animals can heal. Several surveys have been developed trying to better understand the pathogenesis of this type of disease. In this study rabbits experimentally infected with bovine herpesvirus 5 (BoHV-5) were subjected to immunohistochemical and molecular analysis by real time PCR, to describe the inflammatory response in six different regions of his brain. All animals showed severe neurological signs and were euthanized twenty days after the initial infection. Microscopically was described a meningoencephalitis characterized by nonsuppurative meningitis, mononuclear perivascular cuffs and malacia, but were not observed viral inclusion corpuscles. T lymphocytes constituted a high percentage of mononuclear cells involved in neuroinflammation and there were no significant differences in astrocyte response when comparing the experimental and control groups (p> 0.05). The viral quantification by qPCR allowed found viral particles in all brain regions of all experimental animals, being directly proportional to the amount of virus and the visualization of lesions in the brain of rabbits, as well as immunodetection of BoHV-5 by immunohistochemistry. It is possible to suspect a strong engagement of the host immune system that made the majority of animals respond differently compared to the same administered amount of viral inoculum
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Raker, Verena [Verfasser]. "Herpes simplex virus type 1 (HSV-1) infection alters growth factor signaling in primary cortical brain cells / Verena Raker." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2017. http://d-nb.info/1150340320/34.
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