Type I interferon(IFN)inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins.As an IFN-induced protein,myxovirus resistance B(MXB)protein was reported to inhibit multiple highly p...Type I interferon(IFN)inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins.As an IFN-induced protein,myxovirus resistance B(MXB)protein was reported to inhibit multiple highly pathogenic human viruses.It remains to be determined whether MXB employs a common mechanism to restrict different viruses.Here,we find that IFN alters the subcellular localization of hundreds of host proteins,and this IFN effect is partially lost upon MXB depletion.The results of our mechanistic study reveal that MXB recognizes vimentin(VIM)and recruits protein kinase B(AKT)to phosphorylate VIM at amino acid S38,which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes,hence causing a restriction of virus infection.These results highlight a new function of MXB in modulating VIM-mediated trafficking,which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.展开更多
基金appreciate the National Microbial Resource Center(No.NMRC-2020-3)the CAMS Collection Center of Pathogenic Microorganisms(CAMS-CCPM-A)for providing valuable reagents+4 种基金supported by Beijing Natural Science Foundation 7242097(to Dongrong Yi)National Natural Science Foundation of China 81902075(to Dongrong Yi)CAMS Innovation Fund for Medical Sciences 2021-I2M-1-038(to Shan Cen)2021-I2M-1-030(to Quanjie Li)2021-I2M-1-043(to Xiaoyu Li).
文摘Type I interferon(IFN)inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins.As an IFN-induced protein,myxovirus resistance B(MXB)protein was reported to inhibit multiple highly pathogenic human viruses.It remains to be determined whether MXB employs a common mechanism to restrict different viruses.Here,we find that IFN alters the subcellular localization of hundreds of host proteins,and this IFN effect is partially lost upon MXB depletion.The results of our mechanistic study reveal that MXB recognizes vimentin(VIM)and recruits protein kinase B(AKT)to phosphorylate VIM at amino acid S38,which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes,hence causing a restriction of virus infection.These results highlight a new function of MXB in modulating VIM-mediated trafficking,which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.
基金supported by the National Natural Science Foundation of China(31570246 and 32170279)the Fundamental Research Funds for the Central Universities(2572019CT03)。
