tetano
Editor, Senior Moderator
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 S[SUP]1[/SUP], Zickler M[SUP]1[/SUP], Pinho Dos Reis V[SUP]1[/SUP], G?nther T[SUP]1[/SUP], Grundhoff A[SUP]1[/SUP], Reilly PT[SUP]2[/SUP], Mak TW[SUP]3[/SUP], Stanelle-Bertram S[SUP]1[/SUP], Gabriel G[SUP]1,[/SUP][SUP]4[/SUP].
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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[SUP]-/-[/SUP] and ANP32A[SUP]+/+[/SUP] 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[SUP]-/-[/SUP] mice with H3N2 or H5N1 IAV revealed significantly reduced virus loads, inflammatory cytokine response and reduced pathogenicity compared to ANP32B[SUP]+/+[/SUP] mice. Genome-wide transcriptome analyses in ANP32B[SUP]+/+[/SUP] and ANP32B[SUP]-/-[/SUP] 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
Free PMC Article
ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response.
Beck S[SUP]1[/SUP], Zickler M[SUP]1[/SUP], Pinho Dos Reis V[SUP]1[/SUP], G?nther T[SUP]1[/SUP], Grundhoff A[SUP]1[/SUP], Reilly PT[SUP]2[/SUP], Mak TW[SUP]3[/SUP], Stanelle-Bertram S[SUP]1[/SUP], Gabriel G[SUP]1,[/SUP][SUP]4[/SUP].
Author information
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[SUP]-/-[/SUP] and ANP32A[SUP]+/+[/SUP] 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[SUP]-/-[/SUP] mice with H3N2 or H5N1 IAV revealed significantly reduced virus loads, inflammatory cytokine response and reduced pathogenicity compared to ANP32B[SUP]+/+[/SUP] mice. Genome-wide transcriptome analyses in ANP32B[SUP]+/+[/SUP] and ANP32B[SUP]-/-[/SUP] 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
Free PMC Article