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Immune protection and immune pathogenesis of viral infections

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Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4625 - 2013/12/09
Abstract Using the model of lymphocytic choriomeningitis virus (LCMV) in mice we have first investigated antiviral antibody protection against persistent infections. We found that neutralization, Fcγ receptor binding and complement activation were dispensable for antiviral antibody protection in vivo. We demonstrated organ-specific effects of antibodies and the absence of neutralization in primary target organs of the virus. Inhibition of infectious virions release from cells might occur, and antiviral protection could be potentiated by inflammation. Secondly, we studied immunopathological mechanisms of Lassa fever (LF) using the new HHD mouse model in which LCMV-WE infection caused a LF-like disease. We showed that T cell activation of virus-infected macrophages triggered the inducible nitric oxide synthase (iNOS) expression in an interferon-γ (IFN-γ) dependent fashion leading to disease. iNOS-deficient or IFN-γ-depleted HHD mice were indeed fully protected, designating nitric oxide as an essential mediator of the terminal disease characterized by systemic edema, circulatory failure and cardioplegia.
Keywords LCMVAntibody protectionNeutralizationFcγ receptorsComplementLassa feverINOSNitric oxideIFN-γ
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URN: urn:nbn:ch:unige-328906
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REMY, Mélissa. Immune protection and immune pathogenesis of viral infections. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:32890

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Deposited on : 2014-01-08

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