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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
IFI208, an interferon-stimulated gene, promotes host antiviral responses through liquid-liquid phase separation of
Guangqiang Ye1, Jiaxiu Gao1, Xiaohong Liu1
1Division of Fundamental Immunology, State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Abstract:
PYHIN (IFI200/HIN-200) family members are involved in host antiviral immune responses by detecting viral nucleic acids through HIN domains. Within this family, the function of IFI208, which lacks a HIN domain, remains largely unknown. In this study, we identify IFI208, a member of the PYHIN family, as an interferon stimulated gene (ISG). Upon exposure to viral DNA and RNA, IFI208 inhibits viral replication by increasing type I interferon (IFN) production. Mechanistically, upon infection, IFI208 is translocated to the cytoplasm through the chromosome region maintenance 1 (XPO1) transporter protein, and interacts with melanoma differentiation associated gene 5 (MDA5) to enhance the ability of this protein to recognize double stranded RNA (dsRNA) and promote its oligomerization. Taken together, we identify IFI208 as an interferon-stimulated gene (ISG) that induces dsRNA dependent liquid-liquid phase separation of MDA5. Our results indicate that the XPO1-IFI208-MDA5 axis has an important function in the innate responses to viruses.
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