ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response

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Front Immunol. 2020 Mar 13;11:450. doi: 10.3389/fimmu.2020.00450. eCollection 2020.
ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response.


Beck S¹, Zickler M¹, Pinho Dos Reis V¹, G?nther T¹, Grundhoff A¹, Reilly PT², Mak TW³, Stanelle-Bertram S¹, Gabriel G^1,4.

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Abstract

Deciphering complex virus-host interactions is crucial for pandemic preparedness. In this study, we assessed the impact of recently postulated cellular factors ANP32A and ANP32B of influenza A virus (IAV) species specificity on viral pathogenesis in a genetically modified mouse model. Infection of ANP32A^-/- and ANP32A^+/+ mice with a seasonal H3N2 IAV or a highly pathogenic H5N1 human isolate did not result in any significant differences in virus tropism, innate immune response or disease outcome. However, infection of ANP32B^-/- mice with H3N2 or H5N1 IAV revealed significantly reduced virus loads, inflammatory cytokine response and reduced pathogenicity compared to ANP32B^+/+ mice. Genome-wide transcriptome analyses in ANP32B^+/+ and ANP32B^-/- mice further uncovered novel immune-regulatory pathways that correlate with reduced pathogenicity in the absence of ANP32B. These data show that ANP32B but not ANP32A promotes IAV pathogenesis in mice. Moreover, ANP32B might possess a yet unknown immune-modulatory function during IAV infection. Targeting ANP32B or its regulated pathways might therefore pose a new strategy to combat severe influenza.
Copyright ? 2020 Beck, Zickler, Pinho dos Reis, G?nther, Grundhoff, Reilly, Mak, Stanelle-Bertram and Gabriel.



KEYWORDS:

ANP32A; ANP32B; antiviral immunity; influenza A virus; pathogenesis


PMID:32231671PMCID:PMC7083139DOI:10.3389/fimmu.2020.00450
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