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large yellow croaker(larimichthys crocea)mitofusin 2 inhibits type I IFN responses by degrading MAVS via enhanced K48‑linked ubiquitination

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Marine Life Science & Technology 2023年第3期5卷 359-372页

作者： Wen-Xing Li Xiao-Hong Wang Yi-Jun Lin Yuan-Yuan Zhou Jun Li Xiang-Yang Zhang Xin-Hua Chen State Key Laboratory of Mariculture Breeding Key Laboratory of Marine Biotechnology of Fujian ProvinceCollege of Life SciencesCollege of Marine SciencesFujian Agriculture and Forestry UniversityFuzhou 350002China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519000China School of Science and Medicine Lake Superior State UniversitySault Ste.MarieMI 49783USA

In mammals,mitofusin 2(MFN2)is involved in mitochondrial fusion,and suppresses the virus-induced RIG-I-like receptor(RLR)signaling ***,little is known about the function of MFN2 in non-mammalian *** the present study,we cloned an MFN2 ortholog(LcMFN2)in large yellow croaker(larimichthys crocea).Phylogenetic analysis showed that MFN2 emerged after the divergence of amphioxus and *** protein sequences of MFN2 were well conserved from fsh to ***2 was expressed in all the tissues/organs examined at diferent levels,and its expression was upregulated in response to poly(I:C)*** of LcMFN2 inhibited MAVS-induced type I interferon(IFN)promoter activation and antiviral gene *** contrast,knockdown of endogenous LcMFN2 enhanced poly(I:C)induced production of type I ***,LcMFN2 enhanced K48-linked polyubiquitination of MAVS,promoting its ***,overexpression of LcMFN2 impaired the cellular antiviral response,as evidenced by the increased expression of viral genes and more severe cytopathic efects(CPE)in cells infected with spring viremia of carp virus(SVCV).These results indicated that LcMFN2 inhibited type I IFN response by degrading MAVS,suggesting its negative regulatory role in cellular antiviral ***,our study sheds a new light on the regulatory mechanisms of the cellular antiviral response in teleosts.

关键词： large yellow croaker larimichthys crocea MFN2 MAVS Type I IFN response Ubiquitin-proteasome pathway

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