Syk Facilitates Influenza A Virus Replication by Restraining Innate Immunity at the Late Stage of Viral Infection
Yingying Li, Shasha Liu, Yongqin David Chen, Biao Chen, Meng Xiao, Bincai Yang, Kul Raj Rai, Mohamed Maarouf, Guijie Guo, Ji‐Long Chen
Abstract
Innate immunity must be tightly controlled to eliminate invading pathogens while avoiding autoimmune or inflammatory diseases. Syk is essential for STAT1 activation at the early stage of IAV infection, which is critical for initial antiviral responses. Surprisingly, here a time course study showed that Syk suppressed innate immunity during late phases of IAV infection and thereby promoted IAV replication. Syk deficiency enhanced the expression of type I and III interferons, inhibited IAV replication, and rendered mice more resistant to IAV infection. Syk impaired innate immune signaling through impeding TBK1 activation. These data reveal that Syk participates in the initiation of antiviral defense against IAV infection and simultaneously contributes to the restriction of innate immunity at the late stage of viral infection, suggesting that Syk serves a dual function in regulating antiviral responses. This finding provides new insights into complicated mechanisms underlying interaction between virus and host immune system.