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

Fiche publication

Date publication

janvier 2020

Journal

Frontiers in immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr REILLY Patrick

Tous les auteurs :
Beck S, Zickler M, Pinho Dos Reis V, Günther T, Grundhoff A, Reilly PT, Mak TW, Stanelle-Bertram S, Gabriel G

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32231671

Résumé

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.