title: Intracellular osteopontin stabilizes TRAF3 to positively regulate innate antiviral response.
abstract: Osteopontin (OPN) is a multifunctional protein involved in both innate immunity and adaptive immunity. However, the function of OPN, especially the intracellular form OPN (iOPN) on innate antiviral immune response remains elusive. Here, we demonstrated that iOPN is an essential positive regulator to protect the host from virus infection. OPN deficiency or knockdown significantly attenuated virus-induced IRF3 activation, IFN-β production and antiviral response. Consistently, OPN-deficient mice were more susceptible to VSV infection than WT mice. Mechanistically, iOPN was found to interact with tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) and inhibit Triad3A-mediated K48-linked polyubiquitination and degradation of TRAF3 through the C-terminal fragment of iOPN. Therefore, our findings delineated a new function for iOPN to act as a positive regulator in innate antiviral immunity through stabilization of TRAF3.
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Biomedical Translational Research Institute, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Immunology &Key Laboratory of Infection and Immunity of Shandong Province, Shandong University the School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Chengjiang
authors.initials: C
authors.lastname: Gao
mesh_terms: D000072283:A549 Cells; D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D029082:Sendai virus / Q000276:immunology; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D054875:Ubiquitination; D018116:Vesiculovirus / Q000276:immunology
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C506895:SPP1 protein, human; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human; D053495:Osteopontin; D016899:Interferon-beta