KCMF1-mediated influenza A virus PB1 ubiquitination at K653 regulates viral replication
Description
Here, we list the key raw data of the manuscript. If you need more detailed data, please contact us. In this study, we identified a novel host factor that regulates IAV replication both in vitro and in vivo from a pool of 26 candidate E3 ubiquitin ligases. Mechanistically, our findings indicate that KCMF1 interacts with the IAV PB1 and mediates ubiquitination at the K653 site, leading to subsequent proteasomal degradation. A recombinant A/Puerto Rico/8/34 virus harboring the K653R mutation PB1 exhibits enhanced replication and increased pathogenicity, with KCMF1-mediated regulation of PR8 virus proliferation being linked to the K653 site of PB1. Importantly, we also discovered that influenza viruses with mutations at the PB1 K653 site exhibited significant resistance to favipiravir (T-705), an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase approved for the treatment of influenza in Japan.
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Institutions
- Xinxiang Medical University