Mechanisms of Influenza virus uncoating by host factors

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Influenza A viruses (IAVs) are enveloped RNA viruses that cause seasonal epidemics and occasional pandemics. During the late stages of virus host cell entry the IAV particle undergoes viral capsid/shell uncoating, cytosolic release of the infectious genomic segments known as viral ribonucleoproteins (vRNPs), and nuclear import of vRNPs. Viral replication takes place in the nucleus of infected cells. Using siRNA screening and cell biology approaches we identified cellular processes that promote IAV uncoating. Here, I will introduce histone deacetylase 6 (HDAC6), a cytosolic lysine deacetylase with ubiquitin-binding activity, and transportin-1 (TNPO1), an importin that regulates liquid liquid phase separation. Both factors are key regulators of cellular disaggregation and are potentially hijacked by multiple enveloped RNA viruses to establish infection in host cells.