Evasion of antiviral immunity through sequestering of TBK1/IKKε/IRF3 into viral inclusion bodies.

Abstract

Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity.

• Authors: Xiaodong Wu, Xian Qi, Bingqian Qu, Zerui Zhang, Mifang Liang, Chuan Li, Carol J Cardona, Dexin Li, Zheng Xing
• Journal: Journal of virology (J Virol) Vol. 88 Issue 6 Pg. 3067-76 (Mar 2014) ISSN: 1098-5514 [Electronic] United States
• PMID: 24335286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IRF3 protein, human
• Interferon Regulatory Factor-3
• Viral Nonstructural Proteins
• Protein Serine-Threonine Kinases
• TBK1 protein, human
• I-kappa B Kinase

Topics

• Humans
• I-kappa B Kinase (genetics, immunology, metabolism)
• Immune Evasion
• Immunity, Innate
• Inclusion Bodies, Viral (immunology, metabolism)
• Interferon Regulatory Factor-3 (genetics, immunology, metabolism)
• Phlebotomus Fever (immunology, metabolism, virology)
• Phlebovirus (genetics, immunology, metabolism)
• Protein Binding
• Protein Serine-Threonine Kinases (genetics, immunology, metabolism)
• Viral Nonstructural Proteins (immunology, metabolism)