Roles of viral inclusion bodies in innate immune evasion in infection with a novel bunyavirus (INM8P.441)

Abstract

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the family Bunyaviridae. We have previously shown that innate immunity in host cells was modulated in infected cells and antiviral cytokine induction was suppressed by nonstructural protein NSs of SFTSV. In this study, we analyzed the pattern recognition receptors and the signaling pathways for mounting innate defense against viruses. Through studying virus-host interactions, we have explored the strategy exploited by SFTSV to evade host antiviral responses. We found that NSs can form inclusion bodies in infected cells. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during viral replication in infected cells, but their role in viral immune evasion has barely been explored. Interestingly NSs interacted with multiple players in the signaling pathways. Through interacting with tank-binding kinase 1 (TBK1), NSs was able to sequester the IKK complex, including IKKε and IRF3 into IBs, albeit NSs did not interact with IKKε or IRF3 directly. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped into cytoplasmic IBs in SFTSV-infected cells; consequently, IFN-β induction was reduced and viral replication enhanced. Sequestering IKK complex, active IRF3, and other signaling molecules into viral IBs resulting in a reduced IFN response, is a novel mechanism for viruses to evade innate immunity.