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Modulation of cell death and inflammation in Influenza A Virus infection through PB1-F2-specific targeting of host proteins

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Defense Thèse de doctorat : Univ. Genève, 2019 - Sc. Vie - Bioméd. 35 - 2019/12/09
Abstract Influenza A virus (IAV) is a major etiologic agent of acute respiratory infections in humans. Annually, IAV infections lead to 3-5 millions of severe cases and up to 650.000 deaths. Severe IAV pathology is accompanied by excessive inflammatory host responses. Proinflammatory cytokines in IAV infected hosts are predominantly produced by monocytic cells. PB1-F2 is a 90 amino acid IAV accessory protein, modulating inflammatory host responses and cell death. The molecular mechanism underlying these processes was unknown. We identified three novel host protein interactors of viral PB1-F2: AIF, DNAJA3 and NLRP3. We show that AIF and DNAJA3 are involved in cell death modulation and viral replication, albeit in a PB1-F2 independent fashion. In contrast, interaction of PB1-F2 with NLRP3 leads to diminished inflammasome activation. Our data suggests that PB1-F2 binding arrests NLRP3 in its closed conformation, preventing the binding of the licensing kinase Nek7 and ultimately activation and oligomerization of NLRP3.
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URN: urn:nbn:ch:unige-1290723
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BOAL P. T. DE CARVALHO, Inès. Modulation of cell death and inflammation in Influenza A Virus infection through PB1-F2-specific targeting of host proteins. Université de Genève. Thèse, 2019. doi: 10.13097/archive-ouverte/unige:129072 https://archive-ouverte.unige.ch/unige:129072

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Deposited on : 2020-01-20

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