Stiftung Tierärztliche Hochschule Hannover (TiHo)

ANP32B deficiency protects mice from lethal Influenza A virus challenge by dampening the host immune response

Beck, Sebastian; Zickler, Martin; Pinho Dos Reis, Vinícius; Günther, Thomas; Grundhoff, Adam; Reilly, Patrick T; Mak, Tak W; Stanelle-Bertram, Stephanie; Gabriel, Gülşah GND

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.

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Beck, S., Zickler, M., Pinho Dos Reis, V., Günther, T., Grundhoff, A., Reilly, P.T., Mak, T.W., Stanelle-Bertram, S., Gabriel, G., 2020. ANP32B deficiency protects mice from lethal Influenza A virus challenge by dampening the host immune response. Frontiers in immunology 11: 450. https://doi.org/10.3389/fimmu.2020.00450
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