Thesis (Ph. D.)--Ohio State University, 2002. / Title from first page of PDF file. Document formatted into pages; contains xii, 97 p.; also contains graphics (some col.). Includes abstract and vita. Advisor: Ming-Daw Tsai, Dept. of Chemistry. Includes bibliographical references (p. 92-97).

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Influenza A virus (IAV) is a major threat to human health with seasonal epidemics, occasional pandemics and emergence of new highly pathogenic strains from the animal reservoir. Our laboratory has shown that the human Annexin A6 (AnxA6) interacts with the IAV M2 proton channel and limits production of progeny IAV from infected cells. We have found that overexpression of AnxA6 impairs morphogenesis and release of progeny viruses. These findings are supported by another study showing that AnxA6 has a critical role in the late endosomal cholesterol balance and affects IAV replication and propagation in AnxA6-overexpressing cells. However, the molecular mechanism responsible for restriction of IAV morphogenesis by AnxA6 is still unclear. AnxA6 is a calcium-dependent phospholipid-binding protein which plays a major role in cellular events such as regulation of cholesterol homeostasis and membrane organisation or repair. AnxA6 is also implicated in the regulation of intracellular signalling pathways required for IAV infection. In this study, we used a combination of virology, cellular biology and biochemistry approaches to decipher the restriction mechanism of IAV by human AnxA6. We found that AnxA6 down-regulates M2 viral protein expression and impairs viral morphogenesis and budding. We also found that AnxA6 regulates chemokines and cytokines expression during viral infection, suggesting that AnxA6 triggers an innate immune response to IAV by modulating signalling pathways required for viral replication. Finally, we observed that IAV down-regulates AnxA6 expression at mRNA level during early stages of infection and at protein level during late infection, suggesting that IAV has developed a strategy to respond to AnxA6 restriction mechanism during viral infection. We conclude that it is essential to better understand the interaction between human AnxA6 and IAV to elucidate the potential of AnxA6 as an antiviral candidate.

Les espaces clos constituent des lieux où la plupart des pathologies infectieuses sont contractées. Le temps passé et le confinement dans ces environnements favorisent notamment l’émergence et la transmission de certaines viroses respiratoires. Des travaux ont montré que certaines surfaces étaient fréquemment contaminées dans ces espaces. Il a également été mis en évidence un lien entre la présence de virus sur les surfaces et des cas d'infections. Le rôle de l’environnement sur la survie du virus, en particulier la part relative des fomites, bien qu’évoquée, demeure méconnu. Ce travail de recherche vise donc à évaluer la propension des supports à inhiber la transmission des virus. Dans ce contexte, l'objectif de ce travail de thèse est d'étudier les matériaux et produits de construction sur cette question. L'originalité de cette thèse réside dans le développement de méthodologies de contamination pour reproduire la contamination des surfaces par une émission oropharyngée en utilisant un substitut salivaire associé à deux modes de contamination des surfaces : l'aérobiocontamination et le dépôt de gouttelettes. Le suivi des contaminations est assuré par une approche quantitative basée sur l'ARN des particules virales et une approche quantitative basée sur l'infectiosité des particules virales. Les résultats montrent que le virus est capable de conserver une part de son infectiosité après une aérosolisation artificielle. Ils mettent également en évidence la capacité de certains matériaux, tels que le cuivre et le linoléum à affecter le génome viral en fonction du mode de contamination. Néanmoins, certains matériaux permettent de préserver l'infectiosité pendant au moins 24h / Most infectious diseases are contracted in indoor environments. The time spent and the confinement in these spaces fosters the emergence and transmission of certain respiratory viruses. Various studies have shown a link between the presence of viruses on surfaces and infections. The role of the environment on the survival of the virus, particularly the relative share of fomites, although briefly mentioned, remains unknown. This research aims to evaluate the propensity of media to inhibit the transmission of viruses. In this context, the aim of this work is to study the role of building materials and products. The originality of this thesis lies in the development of methodologies to reproduce contaminating surface contamination by oropharyngeal emission, using a saliva substitute associated with two modes of surface contamination: airborne contamination and droplets deposition. Monitoring of contamination is provided by two quantitative approaches. One based on the RNA of the viral particles and the other on the infectivity of viral particles. The results show that the virus is able to retain some of its infectivity after an artificial aerosolization. They also highlight the ability of certain materials, such as copper and the linoleum to affect the viral genome according to the mode of contamination. However, some materials can preserve infectivity for at least 24 hours