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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response
Sebastian Beck1, Martin Zickler1, Vinícius Pinho Dos Reis1
1Viral Zoonosis - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
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.
Insights
Cellular factor ANP32B, not ANP32A, promotes influenza A virus (IAV) pathogenesis in mice. Targeting ANP32B offers a potential strategy against severe influenza infections.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Understanding virus-host interactions is vital for pandemic preparedness.
- Cellular factors ANP32A and ANP32B are implicated in influenza A virus (IAV) species specificity.
Purpose of the Study:
- To investigate the role of ANP32A and ANP32B in IAV pathogenesis using genetically modified mice.
- To determine the impact of these cellular factors on viral tropism, immune response, and disease outcome.
Main Methods:
- Infection of ANP32A knockout (-/-) and wild-type (+/+) mice with H3N2 and H5N1 IAV strains.
- Infection of ANP32B knockout (-/-) and wild-type (+/+) mice with H3N2 and H5N1 IAV strains.
- Genome-wide transcriptome analysis in ANP32B knockout and wild-type mice.
Main Results:
- ANP32A deficiency did not significantly alter IAV tropism, immune response, or disease outcome.
- ANP32B deficiency led to significantly reduced viral loads, inflammatory cytokine response, and pathogenicity in mice infected with H3N2 or H5N1 IAV.
- Transcriptome analysis revealed novel immune-regulatory pathways associated with reduced pathogenicity in ANP32B-deficient mice.
Conclusions:
- ANP32B, but not ANP32A, promotes IAV pathogenesis in a mouse model.
- ANP32B may possess an uncharacterized immune-modulatory function during IAV infection.
- Targeting ANP32B or its associated pathways presents a potential therapeutic strategy for severe influenza.
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