Influenza a Virus Antagonizes Type I and Type II Interferon Responses via SOCS1-dependent Ubiquitination and Degradation of JAK1

Background: Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood.
Methods: In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection.
Results: The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1.
Conclusion: Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.