Dissertations / Theses on the topic 'Virus interactions'
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Murray, Shannon. "Foamy virus-host interactions /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/4987.
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Quax, Tessa. "Archaeal virus-host interactions." Paris 6, 2013. http://www.theses.fr/2013PA066637.
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The work presented in this thesis provides novel insights in several aspects of the molecular biology of Archaea, Bacteria and their viruses. The archaeal virus Sulfolobus islandicus rod-shaped virus 2 (SIRV2), has a remarkable infection cycle. Infection with SIRV2 results in the formation of large virus associated pyramids (VAPs) on the host cell surface. The pyramids open during the final step of the infection cycle, to allow the release of virions. This virus release mechanism is unique. The VAPs are formed by self-assembly of one virus-encoded protein, PVAP. VAPs exist as discrete particles, and are baseless pyramids with heptagonal perimeter. The assembly process of the VAPs is described, based on cryo-electron tomography experiments and mutational analysis of PVAP. VAPs consists of two layers of which the outer one continuous with the cell membrane. PVAP expression in bacterial and eukaryotic cells resulted in VAP formation on nearly all membranes, demonstrating that PVAP serves as a universal membrane remodeling system, which might be exploited for biotechnological purposes. Whole transcriptome sequencing allowed determination of a global map of virus and host gene expression during the infection cycle. Host genes involved in anti-viral defence are activated (i. E. CRISPR-Cas and toxin anti-toxin systems). The multi-subunit protein complexes crucial for CRISPR anti-viral defence have an uneven stoichiometry and are encoded on operons. It is shown that differential translation is a key determinant of modulated expression of genes clustered in operons and that codon bias generally is the best in silico indicator of unequal protein productionLe travail présenté dans cette thèse donne un nouveau regard sur plusieurs aspects de biologie moléculaire des archées, des bactéries et de leurs virus. Le virus Sulfolobus islandicus rod-shaped 2 (SIRV2) a un cycle d’infection remarquable. L’infection par SIRV2 aboutit à la formation sur la surface de la cellule hôte de grandes structures pyramidales associées à ce virus (VAP). Ce mécanisme de libération du virus SIRV2 est unique. Les VAPs sont formées par l’auto-assemblage de la protéine PVAP codée par le virus. Les VAPS peuvent être isolées sous forme de structures compactes et correspondent à des pyramides heptagonales creuses. Le processus d’assemblage des VAPs est décrit, d’après des expériences de cryo-tomographie et d’analyse mutationnelle de PVAP. Les VAPS sont constituées de deux couches dont celle extérieure continue avec la membrane cellulaire. L’expression des PVAP dans les cellules bactériennes et eucaryotiques conduit à la formation de VAPs sur presque toutes les membranes, ce qui démontre que PVAP sert comme un système universel de remodelage des membranes, qui pourrait être utilisé à des fins biotechnologiques. Le séquençage du transcriptome a permis la détermination d’une carte générale de l’expression génique du virus et de l’hôte pendant le cycle d’infection. Les gènes de l’hôte impliqués dans la défense anti-virale sont activés (systèmes CRISPR-Cas et toxine-antitoxine). Il a été démontré que la traduction différentielle est une clef déterminante de l’expression modulée des gènes groupés en opérons et que le biais de codon est généralement le meilleur indicateur in silico de production inégale de protéines
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Asare-Bediako, Elvis. "Brassicaceae : Turnip yellows virus interactions." Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/44041/.
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Turnip yellows virus (TuYV) is the most common and important virus infecting oilseed rape (Brassica napus) in the UK. It causes reductions in growth and seed yield in oilseed rape. Between 2007 and 2010, the prevalence of TuYV in oilseed rape crops in Lincolnshire, Warwickshire and Yorkshire was determined; incidences of infection ranged from 0 and 100%. The highest levels of infection were detected in Lincolnshire and the lowest in Yorkshire. Highest incidences were recorded during 2009-10 and the lowest in 2008-9. Incidences of TuYV were closely related to the flight activities Myzus persicae vector. Most fields showed slightly aggregated pattern of infection during autumn but spring sampling revealed more random patterns. Phylogenetic analysis of both nucleotide and amino acid sequences of the P0 and P3 genes of TuYY revealed three and two genetic groups of TuYV respectively, infecting oilseed rape in Lincolnshire, Warwickshire and Yorkshire. The P0 gene was more variable than the P3 gene and both were under purifying selection. TuYV populations in the three regions were highly structured with limited gene flow between them. Analysis of molecular variance (AMOVA) indicated 96- 97% of the observed variation was due to the variation between isolates within fields. Three RT-PCR assays were developed to differentiate the three genotypes. They successfully detected and discriminated isolates of the two major genotypes from oilseed rape in Lincolnshire. Twenty seven accessions of a B. napus Diversity Fixed Foundation Set (DFFS) screened for resistance against TuYV infections varied in their susceptibility to the virus. An accession Yudal had partial resistance to some but not all the isolates of the two major genetic groups tested. TuYV caused yield losses of up to 44.7% in a glasshouse experiment. A major QTL for the partial TuYV resistance was detected on chromosome C4 (N14), explaining up to 50.5% of the observed resistance.
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Ward, Rebecca. "Bluetongue virus non-structural protein 1 : virus-host interactions." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2006. http://researchonline.lshtm.ac.uk/4646527/.
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Bluetongue virus (BTY) is an orbivirus of the Reoviridae family that infects sheep and other ruminants. BTY has three non-structural proteins, NS I, NS2 and NS3/3A. NS I forms tubular structures and its function is currently unknown. To investigate the role of NS I in BTY infection, the interactions of NS I with mammalian and insect cellular proteins, and BTY viral proteins, were examined. BTY NS I was identi tied as interacting with aldolase A, NUBP 1, Pyruvate kinase M2, cathespin B, SUM 0-1 and peptide TY7 using the yeast two-hybrid system, ELISA and immunofluorescence analysis. TY7 and NS I caused extensive cell death within 24h of co-expression; this cell death was not apoptosis and reduced BTY yield by 37%. The interaction of NS I with SUMO-I and its importance in BTY infection was confinned using siRNA to knockdown SUMO-I during BTY-IO infection. Knockdown of SUMO-I elicited a dramatic reduction in virus yield by 73%. NS I interactions with proteins of the insect vector Culicoides were also examined. A putative interaction between NS 1 and the ubiquitin activating enzyme El (UBA EI) ofCulicoides was identified during screening of a phage library, this has not been confirmed by other means. NS 1 interactions with other BTY proteins were analysed using immunoprecipitation and a strong interaction between NS 1 and YP7 was identified; this was confim1ed using the yeast two-hybrid system and immunoflourescence. Two main roles have been hypothesised for NS I from this data; firstly it is likely that NS I interaction with SUMO-I and UBA E I allows the targeting of specific proteins for sumoylation and ubiquitination allowing NS 1 to modify the host response to BTY infection. Secondly it is possible that NS I serves as an anchor for YP7 and virus cores allowing the build up of cores at the cytoskeleton in close proximity to YP2 for subsequent assembly and release. RNAi against NS J eliminated tubule formation but did not affect virus yield or YP7 and SUMO-J distribution and expression. It is therefore likely that the function of NS I does not rely on tubule fom1ation and that tubules are a form of storage for the active monomer of NSI.
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Kamitani, Mari. "Analysis on virus-virus and virus-host interactions in Brassicaceae in natural environments." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225436.
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Laidlaw, Stephen Mark. "Protein-protein interactions of fowlpox virus." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424671.
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Ji, Xiaoyun. "Molecular interactions within insect virus polyhedra." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540298.
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Orthopoulos, George. "Coxsackie B virus host cell interactions." Thesis, University of Sussex, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419832.
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Ratcliff, Frank Giles. "Novel aspects of plant-virus interactions." Thesis, University of East Anglia, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302040.
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Bryden, Helen. "Host-virus interactions in Hodgkin's disease." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363166.
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Sorensen, George Edwin Peter. "Host-virus interactions in porcine reproductive and respiratory syndrome virus infection." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10040.
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Porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving virus that has significant economic and welfare implications for the pig industry. Vaccination strategies have proved largely ineffective in controlling PRRSV, in some cases even reverting to virulence. An increasing body of evidence suggests a host genetic basis for PRRSV resistance so there is a need to examine the role of host genetics in a biologically relevant in vitro cell culture system. However, PRRSV research is inhibited by the current scarcity of suitable in vitro culture systems. With the aim of developing a convenient in vitro model, porcine bone marrow-derived macrophages (BMDM) were evaluated as a PRRSV cell culture system. BMDM were found to be highly permissive to Type I PRRSV and amenable to genetic manipulation. BMDM proved to be excellent cells for virus production, producing significantly higher titres of PRRSV than commonly used alternative cell types. Surprisingly, PRRSV entry into BMDM was found to be independent of both the prototypic PRRSV receptors, CD163 and CD169, providing further evidence for the existence of alternate PRRSV entry mechanisms in primary cell types. To explore the genetics of pig susceptibility to PRRSV, network-based analysis of host transcriptional datasets, following PRRSV challenge, revealed important differences in co-regulated gene pathways between samples from pigs with different PRRSV-permissiveness. These pathways included genes with important, recently characterised, anti-pathogen activities. The incorporation of network-based transcriptional analysis and published genetic variation data led to the identification of a member of the guanlyate binding protein family, GBP-1, as a candidate host gene involved in controlling PRRSV replication. Overexpression of GBP-1 in BMDM revealed a significant anti-PRRSV function for this protein. Further investigation of published genetic variation in GBP-1 suggested a potential role of this gene in PRRSV tolerance. The results presented in this thesis provide evidence for an alternate PRRSV entry pathway in a biologically relevant cell type. The discovery of a highly PRRSV-infectable cell type with potential for genetic manipulation adds a useful new tool to the area of PRRSV research. The identification of GBP-1 as a novel anti-viral protein with a significant inhibitory effect on PRRSV infection, together with genetic variation in this gene, prompts further research into the genetic basis for PRRSV resistance.
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Pereira, Nelson. "Étude par RMN des interactions entre la nucléoprotéine et la phosphoprotéine de virus appartenant à l’ordre de Mononégavirales." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS406.
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L'interaction entre la nucléoprotéine et la phosphoprotéine est cruciale pour les virus de l'ordre des Mononégavirales. Elle permet à la fois une reconnaissance du matériel génétique viral par le complexe ARN polymérase ARN dépendant du virus et la mise à disposition d'une réserve de nucléoprotéine sous forme monomère pour encapsider spécifiquement les brins d'ARN génomique viral néoformés.Dans le cadre de mon projet doctoral, j'ai pu approfondir les connaissances actuelles concernant cette interaction pour le virus respiratoire syncytial et le virus de la peste-des-petits-ruminants, par l'obtention de données de structure, de dynamique et d'interactions par la technique de résonance magnétique nucléaire.Mon projet, basé sur l'utilisation de la RMN, en tant que technique structurale, s'inscrit dans une collaboration avec l'INRA de Jouy-en-Josas et l'Institut Pasteur de Paris. Ainsi tout au long de ma thèse mes résultats ont pu être mis en rapport avec ceux obtenus par des techniques de biologie fonctionnelle telles que la génétique inverse ou l'utilisation de virus recombinants, mais aussi d'autres techniques de biologie structurale telles que la cristallographieThe interaction between the nucleoprotein and the phosphoprotein is essential for viruses of the Mononegavirales order. It allows the viral genetic material recognition by the RNA dependent RNA polymerase complex and stabilization of the nucleoprotein in a monomeric form so it can be used as a pool to encapsidate neo-synthesized viral genomic RNA.In the framework of my PhD project, I was able to deepen the knowledge about this interaction for the respiratory syncytial virus and the peste-des-petites-ruminants virus, getting data about the structure, dynamics and interactions by the nuclear magnetic resonance technique.My project, based on the use of NMR as a structural technique, takes place within a collaboration with the INRA of Jouy-en-Josas and the Institut Pasteur in Paris. During the preparation of my PhD, I could thus compare my results with those obtained by functional biology techniques like reverse genetics and the use of recombinant virus, but also other structural biology techniques such as crystallography
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Archer, Steffen. "AC electrokinetic studies of virus host interactions." Thesis, University of Glasgow, 1998. http://theses.gla.ac.uk/1198/.
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Major, James R. "Interactions of dendritic cells with vaccinia virus." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401096.
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Wodarz, Dominik. "Mathematical models of virus immune system interactions." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268104.
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Heaney, J. "Immunosuppression and virus-cell interactions in morbilliviruses." Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246332.
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Spyer, Moira Jane. "Respiratory syncytial virus host cell receptor interactions." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269926.
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Tungadi, Trisna Dewi. "Cucumber mosaic virus modifies plant-aphid interactions." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708288.
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Ioannou, Marina. "Cell surface interactions of Coxsackie A9 virus." Thesis, University of Essex, 2018. http://repository.essex.ac.uk/22325/.
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An understanding of how viruses interact with their receptors is vital as this step is a major determinant of host susceptibility and disease. Coxsackievirus A9 (CAV9), an enterovirus, harbours an integrin- recognition motif, RGD (Arg-Gly-Asp), in the capsid protein VP1 and although modes of transmission and pathogenesis are still largely unknown, this motif is believed to be primarily responsible for integrins αvβ6 and αvβ3 binding. The conservation of the RGD +1 position in CAV9 and other picornaviruses showed evidence that this is related to viral tropism and infectiousness of the virus. CAV9 has also been reported to interact with the heparan sulphate/heparin class of proteoglycans (HSPG). This thesis describes work designed to improve our understanding of the involvement of a) the RGD motif and more specifically the RGDX position in CAV9 infection, using a large panel of different RGDX variants and a number of cell lines not previously used in CAV9 research b) the significance of possible interactions between CAV9 and HSPG in infection. Several CAV9 variants were tested in a panel of 8 different cell lines. Infection in each cell line was observed to follow either an RGD- dependant or RGD- independent pathway, although the results did not fully correlate with the receptor expression found on the cell lines used. The RGDX position was found to be critical for efficient infection in cells when an RGD- dependent pathway is used. To understand which integrin is likely to be involved in entry, into one of the RGD-dependent cell lines, A549, blocking antibodies against αvβ3 and αvβ6 were used. Neither antibody gave full protection against CAV9, as has been reported previously, suggesting that other integrins might also be used. Two new HSPG-binding CAV9 mutants were discovered, showing that binding to HSPG can be achieved by several mechanisms. Binding to HSPG was found to be significant in some cells, but not others, again illustrating the complexity of interactions between CAV9 and the cell surface. The results obtained have greatly improved our understanding of how CAV9 infects cells. This will be useful in the design of antivirus drugs and also gives a framework for the modification of CAV9 or other RGD containing picornaviruses for specific targeting of cancer cells for oncolytic therapy.
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Aitken, Angus Iain. "Membrane interactions of plant virus movement proteins." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/15617.
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Plant viruses post a significant risk to both global food security, and industrial agriculture, however very little is known regarding their molecular mechanisms. Despite intensive study since the discovery of a multitude of plant virtual movement proteins, it remains unknown how they transverse the plasmodesmata, and thus move between cells. The CMV virus is widespread, infecting over a thousand plant species, and yet the means by which the movement protein CMV 3a associates to cellular membranes, targets itself and viral genomes to plasmodesmata have not been described. This study initially attempted to purify the CMV 3a protein from bacterial expression for structural and biophysical studies to examine viral protein and host membrane interactions. The study also began mapping the CMV 3a protein surface to investigate protein localisation and membrane attachment in planta, identifying structural features, including two potentially amphipathic helices which bear further investigation for potential roles in membrane association. Finally, this thesis examined the potential for the lipid modification S-acylation (Palmitoylation) as a membrane anchor, across a range of viral movement proteins. Describing this modification of viral movement proteins for the first time, S-acylation was demonstrated to not only be widespread, but potentially play different roles across a range of plant virus movement systems. This information is vital for the advancement of the field's understanding of the cell to cell movement of plant viruses, and the potential development of control strategies; and hence the safeguarding of global food security.
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Fayad, Amer C. "Interactions of soybean Rsv genes and Soybean mosaic virus." Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/11081.
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Soybean mosaic virus (SMV; Genus Potyvirus; Family Potyviridae) is one of the most widespread viruses in soybean (Glycine max [L.] Merr.). Hutcheson, a cultivar developed in Virginia, is resistant to the common strains of SMV. However, new resistance-breaking (RB) isolates of SMV have emerged in natural infections to break the resistance of Hutcheson containing the Rsv1y allele. These RB isolates are SMV-G5 and G6-like based on the differential reactions on soybean cultivars with the Rsv1 locus, and are more G6-like based on the amino acid sequence of the coat protein (CP). The CP of the RB isolates is diverse at the amino and carboxy termini and highly conserved in the core region. RB isolates reduce the yield of susceptible cultivars and cause mottling of the seed coat. Dual infection of soybeans with SMV and BPMV increased the severity of symptoms, including plant stunting and SMV titer in comparison to single SMV inoculations. The reactions of Hutcheson and herbicide-tolerant Hutcheson RR were similar with or without herbicide application. Resistance to SMV is controlled by single dominant genes at three distinct loci, Rsv1, Rsv3 and Rsv4. The mechanisms of resistance at the Rsv3 and Rsv4 loci were investigated by tracking virus accumulation and movement over time using leaf immunoprints. The mechanisms of Rsv3 resistance include extreme resistance, hypersensitive response, or restriction to virus replication and movement, which are strain specific. The Rsv4 gene was found to function in a non-strain specific and non-necrotic manner. The mechanisms of Rsv4 resistance involve restricting both cell-to-cell and long distance movement of SMV. The Rsv1, Rsv3 and Rsv4 resistance genes exhibit a continuum of SMV-soybean interactions, and include complete susceptibility, local and systemic necrosis, restriction of virus movement (both cell-to-cell and long distance), reduction in virus accumulation, and extreme resistance with no detectable virus. Cultivars containing two genes for resistance, Rsv1 and Rsv3 or Rsv1 and Rsv4, were resistant to multiple strains of SMV tested and show great potential for gene pyramiding efforts to ensure a wider and more durable resistance to SMV in soybeans.Ph. D.
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Martin, Caroline. "Hepatitis C virus - cell interactions : comparisons of virus and host lipoprotein binding." Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424130.
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Williams, Cigdem Hayat. "Mutagenesis and virus blocking studies on virus-receptor interactions of Coxsackievirus A9." Thesis, University of Essex, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390959.
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Gaafar, Yahya Zakaria Abdou [Verfasser]. "Plant virus identification and virus-vector-host interactions / Yahya Zakaria Abdou Gaafar." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1220909262/34.
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Perez, Belinda. "Host innate response and virus-host cell interactions in avian influenza virus infection." Thesis, University of Nottingham, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.606257.
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Highly pathogenic avian influenza (HP AI) H5Nl viruses cause devastating fatal disease in chickens, reaching nearly 100% mortality rate within 48 hours. In contrast, ducks show little or no clinical signs. This suggests that there are host species-specific differences in the innate immunity beMeen these two species. Large quantities of HP Al H5Nl viruses have been reported in skeletal muscle of infected chickens and ducks. An in vitro model comprising primary skeletal muscle cells from these two avian species was established to study host immune response 'to avian influenza. Infection with a low pathogenicity avian influenza (LP AI) virus in differentiated chicken muscle cells resulted in a vigorous induction of interferon-fJ and several interferon-inducible genes while two HP Al H5N 1 viruses effectively inhibited this antiviral response. Duck muscle cells did not appear to produce large amounts of type 1 interferons independent of the virus used.
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Keller, Brian Andrew. "Functional Genomic Studies of Vaccinia Virus Provide Fundamental Insights into Virus-Host Interactions." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36614.
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The oncolytic virus field is in the midst of strong and sustained growth. The clinical utility of this class of therapeutics has been bolstered in recent years by the rise of immune checkpoint inhibition, which has the potential to work synergistically with oncolytic viruses to increase the scope of patients who respond favourably to therapy. This growth has been further driven by clear industry support with several pharmaceutical companies acquiring or developing oncolytic virus products following the 2015 FDA approval of Talimogene laherparepvec and the generally-accepted potential of immunotherapeutic approaches to cancer treatment. Vaccinia virus is a double-stranded DNA virus with an extensive history of vaccine use in humans and a desirable safety profile. It is a large virus with a complex lifecycle, and its history of use as a vaccine has resulted in the generation of dozens of unique strains. Although it has been studied extensively, much remains unknown about many vaccinia virus gene function(s) and the virus’ interactions with cellular hosts. Vaccinia virus-based oncolytic viruses have been developed, however clinical outcomes thus far have been unsatisfactory. A more complete understanding of vaccinia virus gene functions must therefore precede the effective design of a next-generation vaccinia virus-based oncolytic candidate. With this downstream goal, we sought to (1) understand the unique oncolytic virus-relevant phenotypic properties of five clinical candidate vaccinia virus strains, and (2) generate and characterize a library of single-gene mutants of the Copenhagen strain of vaccinia virus. These studies resulted in the selection of vaccinia virus-Copenhagen as the wild-type strain of choice that will be utilized for future oncolytic virus development. Furthermore, the generation and initial characterization of an 89-member clonal library of vaccinia-Copenhagen single-gene mutants will be an important tool as we seek to generate a next-generation oncolytic virus candidate. Completed characterization studies challenge the role that viral thymidine kinase should play in oncolytic virus design, demonstrate novel functions of the vaccinia virus gene A47L, and provide an understanding of the role of the vaccinia virus gene F15L. These studies also raise the concept of the personalized selection of oncolytic virotherapeutics. This virus library has the potential to increase the fundamental understanding of vaccinia virus biology in this field as well as in the study of vaccine development and pathogen-host interactions.
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Eid, Fatma Elzahraa Sobhy. "Predicting the Interactions of Viral and Human Proteins." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/77581.
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The world has proven unprepared for deadly viral outbreaks. Designing antiviral drugs and strategies requires a firm understanding of the interactions taken place between the proteins of the virus and human proteins. The current computational models for predicting these interactions consider only single viruses for which extensive prior knowledge is available. The two prediction frameworks in this dissertation, DeNovo and DeNovo-Human, make it possible for the first time to predict the interactions between any viral protein and human proteins. They further helped to answer critical questions about the Zika virus.
DeNovo utilizes concepts from virology, bioinformatics, and machine learning to make predictions for novel viruses possible. It pools protein-protein interactions (PPIs) from different viruses sharing the same host. It further introduces taxonomic partitioning to make the reported performance reflect the situation of predicting for a novel virus. DeNovo avoids the expected low accuracy of such a prediction by introducing a negative sampling scheme that is based on sequence similarity. DeNovo achieved accuracy up to 81% and 86% when predicting for a new viral species and a new viral family, respectively. This result is comparable to the best achieved previously in single virus-host and intra-species PPI prediction cases.
DeNovo predicts PPIs of a novel virus without requiring known PPIs for it, but with a limitation on the number of human proteins it can make predictions against. The second framework, DeNovo-Human, relaxes this limitation by forcing in-network prediction and random sampling while keeping the pooling technique of DeNovo. The accuracy and AUC are both promising ($>85%$, and $>91%$ respectively). DeNovo-Human facilitates predicting the virus-human PPI network.
To demonstrate how the two frameworks can enrich our knowledge about virus behavior, I use them to answer interesting questions about the Zika virus. The research questions examine how the Zika virus enters human cells, fights the innate immune system, and causes microcephaly. The answers obtained are well supported by recently published Zika virus studies.Ph. D.
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Hacker, Kari Ema De Silva Aravinda Manu. "Characterization of dengue virus interactions with host cells." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2009. http://dc.lib.unc.edu/u?/etd,2845.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2009.Title from electronic title page (viewed Jun. 4, 2010). "... in partial fulfillment of the degree of Doctor of Philosophy in the Department of Microbiology and Immunology." Discipline: Microbiology and Immunology; Department/School: Medicine.
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Turner, David Richard. "Protein-RNA interactions in tobacco mosaic virus assembly." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328799.
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LeÌonard, Vincent H. J. "Interactions of Bunyamwera virus N and NSs proteins." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418348.
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Harrison, Thomas Stephen. "Interactions between Human Immunodeficiency Virus and Cryptococcus neoformans." Thesis, St George's, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299059.
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Jones, Angela. "Human dendritic cell interactions with respiratory syncytial virus." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289663.
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Frois-Moniz, Katya. "Host/virus interactions in the marine cyanobacterium prochlorococcus." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/90042.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Civil and Environmental Engineering, 2014.Cataloged from PDF version of thesis.
Includes bibliographical references.
Bacterial viruses shape the diversity, metabolic function, and community dynamics of their microbial hosts. As microbes drive many major biogeochemical cycles, viral infection is therefore a phenomenon of global significance. A significant fraction of primary production in the oceans is performed by the picocyanobacteria Prochlorococcus and Synechococcus. The viruses ('cyanophages') that infect these cyanobacteria are unusual in that their genomes contain a large suite of orthologs to host metabolic genes. These orthologs, known as 'auxiliary metabolic genes' ('AMGs'), encode proteins involved in diverse cellular processes, including photosynthesis, carbon and phosphate metabolism, and nucleotide synthesis. They are thought to benefit phage during infection by redirecting host metabolism towards pathways that promote viral replication. While AMGs are widespread in two Prochlorococcus cyanophage families, the podoviruses and myoviruses, they are rare or completely absent in the third family, the siphoviruses. The overarching goal of this thesis is to understand differences in the infection processes of different cyanophages - in particular, between cyanophages that encode AMGs and those that do not. We hypothesize that the latter group utilizes a fundamentally different infection strategy than AMG-encoding cyanophages, and offer several lines of evidence to support this hypothesis. First, we show that siphoviruses that lack AMGs have highly productive infections, and that host photosynthesis is not impaired during infection. This result is somewhat surprising, as evidence suggests that photosynthesis is supported by AMG-encoded proteins during infection by other cyanophages; however, it is consistent with our observations that unlike the podo- and myoviruses, the siphoviruses do not degrade the host genome during infection, and that the host response to siphovirus infection parallels the metabolic changes effected by AMGs in other cyanophages. These results, along with patterns of siphovirus infection kinetics over the diel light cycle, suggest that siphoviruses utilize a mode of infection that is based on modulating, rather than suppressing, host transcription. Finally, we argue that the suite of metabolic changes that occur during siphovirus infection - and that are effected by AMGs in other cyanophages - are induced by a nitrogen-stress-like response in the host during infection, offering new insights into cyanophage/host coevolution.
by Katya Frois-Moniz.
Ph. D.
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Westwood, Jack Henry. "Cucumber mosaic virus infection and plant-aphid interactions." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608811.
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Wall, Sion Richard. "Host-virus interactions in human papillomavirus mediated disease." Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/55555/.
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Human Papillomavirus (HPV) is the cause of a wide spectrum of disease ranging from benign cutaneous warts to malignant anogenital tumours. Two notable features of HPV diseases are that the viruses are highly tissue specific of individual HPV types and the fact that while HPV infections are common only a minority of infected individuals manifest clinical disease, indicating the importance of host virus interactions. In this thesis two HPV mediated diseases have been examined in detail, cervical cancer and Recurrent Respiratory Papillomatosis. Cervical cancer is a major cause of mortality in women in developing nations. In these countries cervical screening programmes are impractical for logistical reasons and there is much interest in the feasibility of developing preventative vaccines. However, before such agents can be developed it must be established that the same HPV types that cause cervical cancer in industrialised nations are associated with cervical cancer in developing nations and that the local clades of HPV have the same amino acid sequence as putative vaccine strains. This thesis presents a study of the prevalence of cervical HPV infection, HPV type distribution and viral genetics carried out in a previously unstudied population of 934 women in rural Gambia. A high cervical HPV prevalence is observed, the most common high risk types were found to be HPV-16 & -35, the former being the most common high risk type worldwide and the latter this study show may be underestimated in African populations. Sequencing of the HPV L1 open reading frames provided data which may have implications for vaccine research. RRP is a rare disease characterised by the presence of papillomata on the larynx and other sites in the upper aerodigestive tract. RRP is usually caused by HPV-6 or -11, two viruses more commonly associated with genital warts. RRP is thought to be contracted from the genital tract. However, genital HPV infection is common yet RRP remains a rare disease, therefore other factors either from the virus or the host must modulate disease pathogenesis. In order to elucidate if RRP is caused by unique HPV clades that might be particularly well adapted to the larynx, the L1 major capsid gene and the oncogenes E6 & E7 have been sequenced. In order to establish the sequence of "normal" genital HPV-11 and to exclude regional differences between UK and US HPV-6 and HPV-11, genital wart tissue from 37 UK donors has also been analysed and compared to papilloma material from 53 RRP patients. Significant sequence differences between RRP and Genital Wart E6 & E7 ORF were observed. In order to examine the possible role of host immunogenetic factors in the pathogenesis of RRP, 50 individuals with RRP were then HLA class typed. A significant association between the HLA class II allele DRB*0301 was found along with a negative association with the HLA DQB1*03 allele. Finally, T-cell proliferation studies using Cytokine Bead Array to detect cytokine production revealed that DQBT03 positive donors produce more IFN-y in response to HPV peptides than DQB1*03 negative individuals.
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Baudin, Maria. "Rift Valley fever : consequences of virus-host interactions." Doctoral thesis, Umeå universitet, Virologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126602.
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Rift Valley fever virus (RVFV) is a mosquito-borne virus which has the ability to infect a large variety of animals including humans in Africa and Arabian Peninsula. The abortion rate among these animals are close to 100%, and young animals develop severe disease which often are lethal. In humans, Rift Valley fever (RVF) presents in most cases as a mild illness with influenza-like symptoms. However, in about 8% of the cases it progresses into a more severe disease with a high case fatality rate. Since there is such a high abortion rate among infected animals, a link between human miscarriage and RVFV has been suggested, but never proven. We could in paper I for the first time show an association between acute RVFV infection and miscarriage in humans. We observed an increase in pregnant women arriving at the Port Sudan Hospital with fever of unknown origin, and several of the patients experienced miscarriage. When we analysed their blood samples for several viral diseases we found that many had an acute RVFV infection and of these, 54% experienced a miscarriage. The odds of having a miscarriage was 7 times higher for RVFV patients compared to the RVFV negative women of which only 12% miscarried. These results indicated that RVFV infection could be a contributing factor to miscarriage. RVFV is an enveloped virus containing the viral glycoproteins n and c (Gn and Gc respectively), where Gn most likely is responsible for the initial cellular contact. The protein DC-SIGN on dendritic cells and the glycosaminoglycan heparan sulfate has been suggested as cellular receptors for RVFV, however other mechanisms are probably also involved in binding and entry. Charge is a driving force for molecular interaction and has been shown to be important for cellular attachment of several viruses, and in paper II we could show that when the charge around the cells was altered, the infection was affected. We also showed that Gn most likely has a positive charge at a physiological pH. When we added negatively charged molecules to the viral particles before infection, we observed a decreased infection efficiency, which we also observed after removal of carbohydrate structures from the cell surface. Our results suggested that the cellular interaction partner for initial attachment is a negatively charged carbohydrate. Further investigations into the mechanisms of RVFV cellular interactions has to be undertaken in order to understand, and ultimately prevent, infection and disease. There is currently no vaccine approved for human use and no specific treatments for RVF, so there is a great need for developing safe effective drugs targeting this virus. We designed a whole-cell based high-throughput screen (HTS) assay which we used to screen libraries of small molecular compounds for anti-RVFV properties. After dose-response and toxicity analysis of the initial hits, we identified six safe and effective inhibitors of RVFV infection that with further testing could become drug candidates for treatment of RVF. This study demonstrated the application of HTS using a whole-cell virus replication reporter gene assay as an effective method to identify novel compounds with potential antiviral activity against RVFV.
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Rowley, J. C. "Virus-host interactions in early HIV-1 infection." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1463445/.
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After entry into a target cell, HIV-1 must traverse the cytoplasm and enter the nucleus in order to integrate into host chromatin. Until recently, the viral CA core was thought to play a passive role in infection, simply delivering its contents to the cytoplasm soon after entry. However, CA has recently been found to interact with and/or determine interaction with several nuclear entry cofactors. In this study, we investigate the consequences of CA interacting with the host mRNA-processing factor CPSF6. We provide evidence that the interaction between CA and cytoplasmic CPSF6 during early infection dictates the downstream nuclear entry pathway and integration site selection of HIV-1, despite not affecting viral titre in cell lines. We identify clinically relevant CTL escape mutations that lie within the CPSF6 binding pocket of CA and alter the relationship of HIV-1 with the CPSF6-dependent nuclear entry pathway. The phenotypes of these mutants suggest that conservation of this pathway is important in vivo but also that the pathway differs between cell types. In addition, we examine the antiviral mechanisms of C-terminal truncations of CPSF6 and the small-molecule CPSF6 peptidomimetics PF74 and BI-1. We design a series of compounds predicted to interact with the CPSF6-binding pocket of CA and screen them for antiviral activity as well as the ability to alter the nuclear entry pathway of HIV-1. Of particular interest are a compound that exhibits a very different inhibition profile from PF74/BI-1 and a compound that causes the virus to use a CPSF6-independent nuclear entry pathway without reducing viral titre. Together, the findings in this study confirm and characterise the role of CPSF6 as an HIV-1 cofactor and demonstrate that drugs targeting the CA-CPSF6 interaction could inhibit the virus through multiple different mechanisms.
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Baldridge, Gerald Don. "Molecular biology of Bunyavirus-host interactions." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184934.
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Ribonuclease T1 oligonucleotide fingerprint (ONF) analysis was used to study genomic stability of La Crosse virus (Bunyaviridae) during vertical and horizontal transmission in the laboratory. No RNA genomic changes were detected in vertebrate cell culture-propagated virus isolated (following oral ingestion and replication) from the natural mosquito host, Aedes triseriatus. Genomic changes were not detected during transovarial passage of virus through two generations of mosquitoes or in virus isolated from suckling mice infected by transovarially infected mosquitoes. These results demonstrate that the La Crosse virus genome can remain relatively stable during transovarial transmission (TOT) in the insect host and during transfer between insect and vertebrate hosts. ONF analysis was used to demonstrate TOT of reassortant California serogroup bunyaviruses in Aedes treiseriatus. Mosquitoes were simultaneously inoculated with temperature sensitive mutants of La Crosse and Snowshoe hare viruses able to replicate at 33°C but not at 40°C. Putative reassortants, selected by replication at 40°C, were isolated from progeny mosquitoes and mice infected by these mosquitoes. ONF analysis confirmed that they were reassortants. Approximately 75% of the M segment and 25% of the L segment nucleotide sequences of Inkoo virus (Bunyaviridae) were determined by Sanger dideoxynucleotide sequencing of cDNA clones. Comparison of the M segment nucleotide and deduced amino acid sequences with those of four other bunyaviruses, representing two serogroups, revealed greater conservation of nucleotide than of amino acid sequence between serogroups. Areas of the sequences representing nonstructural protein(s) were less conserved than glycoprotein regions. The L segment nucleotide sequence begins with the known 3' end of the viral L segment and contains an open reading frame encoding the amino terminal 505 amino acids of the viral L protein. The amino acid sequence contains the glycine-aspartate-aspartate motif which is conserved in many RNA-dependent RNA polymerases. Comparison of the L segment sequences with those in the GEN Bank Data Base revealed no significant similarities with any other sequence.
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Smith, H. G. "Comparative epidemiology and host : Virus interactions of beet yellow virus and beet mild yellowing virus in sugar beet." Thesis, University of East Anglia, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374298.
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Nasheri, Ardekan Neda. "Development of Biomolecular Tools for Studying Host-Virus Interactions of the Hepatitis C Virus." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32480.
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Hepatitis C virus (HCV) is a growing health concern in Canada and around the world, as it currently infects 3% of the global population. While there is no vaccine available against this virus, novel and effective treatment regimens have improved prospects for the cure of HCV. Complications caused by HCV can lead to severe liver disease and even death. The limited viral proteome forces HCV to rely heavily on various host factors for its replication. Additionally HCV modulates the host physiology to facilitate its pathogenesis; consequently, the in dept study of essential host-virus interactions expands our understandingof how the virus and related species commandere host cell machinery. This understanding can help create new therapeutic strategies, which may have applications towards HCV and other related RNA viruses.
While numerous studies have demonstrated that HCV modulates the abundance of various host proteins, the systematic study of the virus’s effect on the enzymatic activity has been relatively unexplored. For this reason, activity-based protein profiling (ABPP) was applied to study the changes in the activity of host enzymes during HCV replication. ABPP is a functional proteomics technique that employs active site-directed probe (ABP) to report on the activity of enzymes within complex proteomes, such as living cells. Herein, directed and non-directed ABPs were employed for specific as well as global profiling of the alterations in the activity of cellular enzymes during HCV replication. As a result, essential host enzymes that are differentially active during HCV infection were identified. Furthermore, I have developed a quantitative ABPP method for relative quantification of the cellular enzymes activity during HCV infection. These results contribute to the discovery of disease-associated biomarkers, with diagnostic significance, and aid in the identification of potential targets for therapeutic interventions. In addition to developing protein-based tools to study host-virus interactions, I employed a novel technique to investigate the interactions of micro-RNA 122 (miR-122), an essential HCV host factor, with the viral RNA genome. This in vitro screening approach, interrogates the folding of HCV RNA using viral RNA-coated magnetic bead (VRB) to determine target site accessibility for RNA silencing. This method predicts the relative affinity of small RNAs towards HCV genomic RNA that are not easily predicted by informatic means, and led to discovery of potent miR-122 interaction site within the large, highly-structured HCV RNA genome. For that reason, VRB assay may represent an attractive tool for the examination of target site accessibility for RNA silencing.
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Foster, Rosalinda Gram. "Virus-Host Interactions in the Development of Avian Leukosis Virus-Induced Osteopetrosis: a Dissertation." eScholarship@UMMS, 1993. https://escholarship.umassmed.edu/gsbs_diss/180.
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Avian leukosis virus (ALV)-induced osteopetrosis is a proliferative disorder of the bone affecting the growth and differentiation of osteoblasts. Osteopetrosis is a polyclonal disease in which cells of the bone contain, on average, multiple viral DNA copies. Osteopetrotic bone is also characterized by the accumulation of unintegrated viral DNA, suggesting an atypical life cycle of the virus in the infected osteoblasts. To better understand virus-host interactions in the induction of osteopetrosis by ALVs, infected chick osteoblast cultures and osteopetrotic bone were examined for aspects of the virus life cycle and effects of infection on osteoblast function.
Levels of infection and virus expression were compared in cultured osteoblasts and osteopetrotic bone. Osteopetrotic bone contained higher levels of viral DNA and correspondingly higher levels of viral proteins than infected osteoblast cultures, suggesting a higher viral load in the diseased bone. A significant level of mature Gag protein was present in the bone, suggesting the accumulation of mature virus particles in the diseased bone. It is possible that the accumulation of virus could facilitate the high levels of infection observed in the diseased bone.
The mechanism by which unintegrated viral DNA persisted in osteopetrotic bone was investigated by examining the susceptibility of infected osteoblasts to superinfection. The results indicated that, in culture, infected osteoblasts were able to establish interference to superinfection. This suggests that the persistence of unintegrated viral DNA in osteopetrotic bone may not result from the continuing infection of productively infected osteoblasts.
The effect of virus infection on osteoblast function was examined in the diseased bone and in osteoblast cultures. In infected chickens, osteoblast activity, as evidenced by the expression of osteoblast phenotypic markers, was increased only in chickens developing severe osteopetrosis. In culture, virus infection had no apparent effect on either the proliferation or differentiation of osteoblasts. This indicates that infection was itself not sufficient to perturb osteoblast function. Furthermore, it suggested that additional components of the bone may be required for ALV infection to induce the abnormal activity of osteoblasts observed in osteopetrosis.
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Sanguino, Casado Laura. "Exploration des interactions virus-hôte et leur importance pour l'adaptation microbienne à travers du CRISPRs." Thesis, Ecully, Ecole centrale de Lyon, 2015. http://www.theses.fr/2015ECDL0033/document.
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Les interactions entre les membres d'une communauté microbienne peuvent être un moyen d'adaptation dans l'environnement. Parmi les nombreuses interactions qui ont lieu dans un écosystème et qui joue un rôle majeur sur la diversité et la dynamique des populations microbiennes est celui des virus procaryotes et leurs hôtes. Les virus peuvent également arbitrer le transfert de matériel génétique entre les procaryotes (transduction), qui pourrait être un mécanisme d'adaptation rapide. Afin de déterminer l'impact potentiel des virus et la transduction, nous avons besoin d'une meilleure compréhension de la dynamique des interactions entre virus et leurs hôtes dans l'environnement. Les données sur les virus de l'environnement sont rares, et les méthodes pour le suivi de leurs interactions avec les procaryotes sont nécessaires. Clustered regularly interspaced short palindromic repeats (CRISPRs), qui contiennent des séquences virales dans les génomes bactériens, pourraient aider à documenter l'histoire des interactions virus-hôte dans l'environnement. Ainsi, cette thèse vise à explorer les interactions virus-hôte dans un environnement donné à travers du séquences CRISPR.Les virus de la cryosphère sont considérés comme abondantes, très actif et avec de larges gammes d'hôtes. Ces caractéristiques pourraient faire de la transduction virale, un facteur clé pour l’adaptation microbienne dans ces environnements. Des métagénomes publics créés à partir des environnements avec une gamme de températures différents ont été examinés. De cette manière, certaines dynamiques d'interactions virus-hôte se sont révélées comme ayant une corrélation avec la température. Un flux de travail a ensuite été développé pour créer un réseau reliant les virus et leurs hôtes en utilisant des séquences CRISPR obtenus à partir de données métagénomiques de la glace des glaciers et du sol de l'Arctique. La création de réseaux d'infection à traves du CRISPRs a fourni une nouvelle perspective sur les interactions virus-hôte. En outre, nous avons cherché des événements de transduction dans les données métagénomiques par la recherche de séquences virales contenant de l'ADN microbien. L’analyse indiquée que les bactériophages du Ralstonia pourraient être des agents de transduction dans la glace des glaciers de l'ArctiqueInteractions between the members of a microbial community can be a means of adaptation in the environment. Among the many interactions that take place in an ecosystem and have been seen to play a major role on microbial diversity and population dynamics is that of prokaryotic viruses and their hosts. Viruses can also mediate the transfer of genetic material between prokaryotes (transduction), which could be a mechanism for rapid adaptation. In order to determine the potential impact of viruses and transduction, we need a better understanding of the dynamics of interactions between viruses and their hosts in the environment. Data on environmental viruses are scarce, and methods for tracking their interactions with prokaryotes are needed. Clustered regularly interspaced short palindromic repeats (CRISPRs), which contain viral sequences in bacterial genomes, might help document the history of virus-host interactions in the environment. Thus, this thesis aimed to explore virus-host interactions in a given environment through CRISPRs. Viruses in the cryosphere have been seen to be abundant, highly active and with broad host ranges. These characteristics could make viral transduction a key driver of adaptation in these environments. Public metagenomes created from environments over a range of temperatures were examined through sequence and CRISPR analysis. In this fashion, certain virus-host interaction dynamics were found to have a correlation with temperature. A workflow was then developed to create a network linking viruses and their hosts using CRISPR sequences obtained from metagenomic data from Arctic glacial ice and soil. The creation of CRISPR-based infection networks provided a new perspective on virus-host interactions in glacial ice. Moreover, we searched for transduction events in metagenomic data by looking for viral sequences containing microbial DNA. Further analysis of the viral sequences in the CRISPRs indicated that Ralstonia phages might be agents of transduction in Arctic glacial ice
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Carr, Tyrell. "Genetic and molecular investigation of compatible plant-virus interactions." [Ames, Iowa : Iowa State University], 2007.
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Zemmel, Rodney W. "Rev-RRE interactions in human immunodeficiency virus gene expression." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390234.
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Jiang, Wen Rong. "Interactions of louping ill virus with a neutralising antibody." Thesis, Oxford Brookes University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261947.
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Munday, Diane Carolyn. "Analysis of human respiratory syncytial virus-host cell interactions." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634755.
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Human respiratory syncytial virus (HRSV) is the leading cause of serious lower respiratory tract disease in infants worldwide. Other high risk groups include the elderly and immunocompromised but HRSV can cause disease in all ages and infections recur throughout life. There is no approved vaccine available and costly antiviral therapies are inefficient for general use. HRSV infection therefore presents a significant healthcare and economic burden. The aims of this study were to investigate the HRSV-host cell interactions and examine the host response to infection via alterations to .the cellular proteome with a view to identifying the pathways, processes and organelles which play a key role in virus infection. Viral RNA synthesis and virion assembly occur in the cytoplasm inducing a stress response as replication alters host cell gene expression. To study this, large scale quantitative proteomics was used to analyse HRSV interactions with cytoplasmic, nuclear and mitochondrial proteomes. Underpinning this was stable isotope labelling with amino acids in cell culture (SILAC) coupled to LC-MS/MS, allowing the simultaneous identification and quantification of cellular and viral proteins. Canonical pathways and specific protein abundance and/or re-localisation changes highlighted by the data sets were validated and characterised using immunoblot analysis, confocal microscopy and functional assays. This allowed a complex picture of virus-host cell interactions to be assembled: novel changes in cell cycle proteins, sub-nuclear structures and mitochondrial function were observed. Proteins involved in the immune proteins converged on mitochondria in HRSV-infected cells and mitochondrial proteome alterations led to the functional analysis of the mitochondrial receptor, Tom70 and its chaperone Hsp90 which were found to play antiviral and pro-viral roles in HRSV biology, respectively. The findings of this study have increased our understanding of the cellular the pathways, processes and organelles which play key roles in RNA-virus infection and highlighted potential targets for therapeutic intervention.
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Damay, Isabelle Colette Geneviève. "Analysis of the bean yellow dwarf virus host interactions." Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426567.
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Caller, Laura Grace. "An investigation into BK Polyomavirus and host-virus interactions." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/288073.
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The potentially oncogenic human pathogen BK Polyomavirus (BKPyV) was first identified in 1971 and has since been associated with a number of diseases primarily in immunosuppressed patients. Infection is established in early life and by adulthood up to 90% of populations show seroconversion for the major capsid protein VP1. Despite this infections are rarely cleared, maintaining a silent asymptomatic persistence punctuated with periods of viral shedding in the urine. The virus is non-enveloped and comprises a simple ~5.2 Kb dsDNA genome which expresses just seven known proteins, necessitating a heavy reliance on, and interactions with, host mechanisms in order to efficiently replicate and disseminate within a population. The poorly understood lifelong persistence and failure to clear infection highlights our lack of understanding of the viral life cycle and viral interactions with host processes and responses to infection. Indeed, non-enveloped viruses are thought to spread solely through infected cell lysis but such large-scale lysis should trigger an acute inflammatory response, which is rarely seen in healthy immunocompetent individuals. The research conducted for this thesis first investigates the egress of BKPyV in a non-lytic manner, presenting evidence for an active non-lytic method of viral egress that is dependent on cellular anion homeostasis. Moreover, data generated for this thesis suggests that virions egress via an unconventional secretion pathway which traffics directly from the endoplasmic reticulum (ER) to the plasma membrane in single-membraned vesicles. Further research undertook a whole cell quantitative temporal viromic (QTV) approach, post-experimentally tagging whole cell lysate peptides with isobaric labels (Tandem Mass Tagging, TMT) to provide a greater understanding of host cell proteomic changes throughout BKPyV infection in two primary human cell types over 72 hours of infection. Such an approach identified ~9000 cellular proteins, of which a surprisingly small number changed significantly in abundance in response to BKPyV infection. Of those that were changed in abundance a large proportion were related to cell cycle, revealing that BKPyV infection induces a pseudo-G2 arrest, similar to the G2/M checkpoint. Validation of TMT results in both cell types provided confidence in this robust data set, and further studies highlighted the importance of not only cell cycle status, but the activity of CDK1 for efficient viral infection and replication. Additionally, TMT generated data emphasised the lack of innate immune induction in response to BKPyV infection, suggesting BKPyV exhibits a sophisticated evasion of pathogen recognition.
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Lumb, Hayley Joy. "Probing protein-protein interactions from human respiratory syncytial virus." Thesis, Durham University, 2018. http://etheses.dur.ac.uk/12479/.
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Human respiratory syncytial virus (hRSV) is the leading cause of viral respiratory tract infections in children.1 In 2013 there were over 60 000 infants hospitalised in the USA alone and the virus resulted in approximately 2.1 million outpatient visits by children under 5 years old.2 The virus leaves the lungs weakened and open to further secondary infections such as bronchitis and pneumonia, especially in immunocompromised and elderly patients. Infections can lead to long-term effects and up to 70% of infants are left with respiratory problems for up to 10 years following hRSV bronchiolitis.3 For otherwise healthy children the treatment is usually supportive, using hydration and additional oxygen.1 Previous antiviral agents and decongestants have been used to little positive effect, leading to the need for new antiviral agents. In the work described in this thesis, key protein targets have been identified from the 11 protein hRSV Genomes. It has been found that F, M2-1, M and N are integral for structural roles, transcription and virus maturation.4 M2-1 protein is a transcription factor and has long been a target for structural biologists due to its integral role in the virus. Chapter 2 describes the characterisation of the protein using biophysical techniques to obtain data on its stability and overall fold. Further work to crystallise the protein is also included.5 Chapter 3 builds on this work introducing the interaction between matrix protein and M2-1. The interaction is characterised through Surface Plasmon Resonance (SPR) and Fluorescence Anisotropy (FA), which gave equilibrium constants and thermodynamic pathways for the first time. Chapter 4 introduces the interaction between hRSV matrix protein and hRSV fusion protein. Previous work has characterised the fusion protein and identified that the cytoplasmic tail is the key subunit which binds to matrix protein.6 Through mutagenesis of a single residue, F572 was identified as the key binding residue.7 The terminal six amino acids were used to form a peptide which formed the basis for the experiments in this thesis. The work described here presents in vitro data which will build on the published literature to further understand the interaction. SPR and FA provide experimental evidence for a hypothetical binding model. This binding model and the resulting equilibrium constants are discussed and evaluated. The X-ray crystal structure of hRSV N protein is known8,9 and this information can be used to design ligands with the aim of disrupting the protein’s function. The work outlined here aimed to evaluate the binding of a series of ligands that were identified by Arrow Therapeutics Ltd as having antiviral activity.10 Thermal shift assays were used to understand the stabilisation of the protein in the presence of the ligand. Dynamic light scattering showed the formation of aggregates of protein when exposed to various concentrations of ligand. Cryo-electron microscopy shows association of the ligand to the protein and the consequent aggregates which form. This provided an indication of how the ligands could interact with the protein and suggests possible modes of action. In Chapter 6, hRSV M protein’s interaction with hRSV F was further investigated. The interaction is key for the maturation of the virus11 and if the binding could be diminished, the infectivity of the virus would suffer. A pocket at the dimer interface was identified, which opened up an opportunity for computational docking studies. Through the application of biophysical techniques and computational methods,12 novel ligands were identified and the initial characterisation of their effect on protein stability was probed. Key protein interactions which are involved in the maturation of the virus and its fusion to the host cell have been characterised and evaluated in this thesis. The opening chapters begin within basic protein characterisation and build to show protein interactions in vitro. In the later chapters, ligand subsets are identified with the aim of disrupting protein interactions or the protein folding. Characterisation of the protein ligand interactions showed protein changes and destabilisation, leading the way for further studies.
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Edwards, Matthew J. "Interactions of monoclonal antibodies with an influenza A virus." Thesis, University of Warwick, 1999. http://wrap.warwick.ac.uk/113445/.
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This investigation examines the efficiency and mechanism of neutralization of influenza A/PR/8/34 virus by three haemagglutinin (HA)-specific monoclonal IgGs (H36, H37 and H9) and their Fabs. The efficiency of neutralization by the Fabs was lower than that of their IgGs. This was concentration-dependent: 50% neutralization (N50) required 104- to 375-fold more Fab than IgG, and at N$ > o required 15- to 208- fold more Fab than IgG. Affinities of the IgGs and Fabs were very similar and thus did not contribute to the difference in their neutralization efficiencies. The mechanism of neutralization of influenza virus by the IgGs was complex. At N90, the majority of the loss of infectivity was attributable to inhibition of virus attachment to cells, whilst at N50 inhibition of attachment accounted for only a minority of the infectivity loss, with the majority attributed to inhibition of fusion. In between N50 and N90 both mechanisms operate simultaneously. In contrast, inhibition of attachment by the H36 and H37 Fabs was the dominant mechanism of neutralization throughout the range of concentrations studied. The H9 Fab did not inhibit virus- attachment, but inhibited virus-cell fusion. Therefore, it was concluded that the difference between the IgGs and their Fabs was the ability of the IgGs to display simultaneous neutralization mechanisms. Post-attachment neutralization (PAN) provides compelling evidence of the ability of antibodies to neutralize by mechanisms other than inhibition of attachment. H36, H37 and H9 IgGs and their Fabs gave PAN at 4°C and 37°C. Efficiency of PAN by the IgGs was lower than the standard neutralization of free virus (STAN). The efficiency of PAN and STAN by the Fabs was similar, except for H9 Fab whose PAN activity was significantly greater than its STAN activity. The mechanism of PAN by both IgGs and their Fabs was inhibition of fusion. The HA of influenza A/PR/8/34 virus goes through a series of conformational intermediates in the fusion process. Examination of the pre-fusion intermediate (created by treating at pH 5 and 4°C) using conformation-specific MAbs detected changes in the viral HA, but these were less extensive than in virus treated at pH 5 and 37°C (post-fusion conformation). The pre-fusion intermediate does not cause fusion, but is a fusion-committed state, as it can subsequently undergo fusion at high efficiency at pH 7.5 when the temperature is raised to 37°C. IgGs and Fabs did not inhibit the haemolysis of CRBCs by the pre-fusion intermediate, nor did they inhibit the conformational changes of the HA that trigger the fusion process. It was concluded that these antibodies interfere sterically with events that occur prior to the formation of the pre-fusion intermediate. The point at which neutralization becomes irreversible was investigated using the three IgGs and a monoclonal IgA. Neutralization of virus in solution was shown to be reversible by removing antibody from the virus with ammonium hydroxide (pH 11.5) (AmOH). The reversibility of neutralization was also examined under conditions designed to mimic the early steps in the virus infectious cycle, (1) virus attachment to cells and (2) low pH-induced virus-cell fusion. Neutralization could be reversed by removal of antibody with AmOH, after neutralization of (1) virus attached to cells and (2) after low pH treatment of virus attached to cells. This suggested that these MAbs do not trigger a permanent loss of virus infectivity, but are required to be bound to the virus for the duration of the neutralization process.