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Contribution de la protéine PB1-F2 des virus influenza A dans l’adaptation d’une souche virale à son hôte

Abstract : Influenza A viruses (IAV) cause flu in birds and some mammals, including humans. They are an important issue for both veterinary and human health. The PB1-F2 protein is an IAV virulence factor whose functions depends on the host as well as the viral strain. The molecular mechanisms associated with PB1-F2 are still enigmatic, but its ability to modulate the host immune response suggests that PB1-F2 contributes to viral fitness. Our work aimed to compare the properties of PB1-F2 in avian and mammalian hosts. In cellular models, an avian H7N1 PB1-F2 had no effect on the host response whereas a human H3N2 PB1-F2 was pro-inflammatory. Conversely, PB1-F2 H7N1 exacerbated the virulence in mice and promoted a strong inflammatory response. Surprisingly, a chimeric H3N2 virus expressing the avian PB1-F2 induced a reduced inflammation in mice compared to H3N2 wild type virus. Thus, the functions of PB1-F2 are not strictly transposable and strongly depend on the viral context in which it is expressed. Finally, we have mapped the interactions between PB1-F2 and host proteins in avian and human cells using the biotin ligase BioID2. We have identified both specific and common PB1-F2 regulated biological pathways. Our work provides elements characterizing the functions of PB1-F2 in avian and mammalian hosts but also in crossing host species barrier or with a reassortant virus expressing an avian PB1-F2
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Submitted on : Friday, October 22, 2021 - 4:31:42 PM
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  • HAL Id : tel-03396305, version 1

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Joëlle Mettier. Contribution de la protéine PB1-F2 des virus influenza A dans l’adaptation d’une souche virale à son hôte. Virologie. Université Paris-Saclay, 2021. Français. ⟨NNT : 2021UPASB034⟩. ⟨tel-03396305⟩

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