干扰素诱导跨膜蛋白抗病毒机制研究进展
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摘要
干扰素诱导跨膜蛋白(IFITM)是一类新型抗病毒细胞防御分子,其在人体组织细胞中普遍表达,主要定位于质膜、内体及溶酶体中,这些部位是病毒侵入细胞的主要靶点。IFITM通过抑制病毒与宿主细胞间的膜融合,从而限制多种病毒侵染,包括埃博拉病毒、流感病毒、严重急性呼吸综合征(SARS)冠状病毒、登革热病毒、西尼罗病毒和寨卡病毒等。虽然,IFITM已经被证明可以抑制8个病毒科数十种病毒,而且其主要抑制病毒进入阶段的融合过程,但IFITM抗病毒机制尚未明确。近年来IFITM的抗病毒作用及其机制已成为相关领域的研究热点。现就IFITM抗病毒谱及抗病毒机制研究进展作一综述。
Interferon-induced transmembrane proteins(IFITMs), a class of novel discovered viral restriction factors, are widely expressed in human tissue cells, mainly located in plasma membrane and endolysosomal comparments, which are the main targets of the virus entry. By inhibiting membrane fusion between virus and cell membrane, IFITMs restrict the entry of a broad spectrum of viruses, including Ebola virus, influenza A virus, severe acute respiratory syndromes(SARS) coronavirus, dengue virus, West Nile virus and Zika virus. Although IFITM has been shown to be able to suppress the infection of virus of the eight virus families, and it primarily inhibits the fusion process of the virus entry stage, but the mechanism of IFITM antiviral activity remains unknown. In recent years, the antiviral effect of IFITM and its mechanism has become a hotspot in related fields. Here the recent advance of IFITM's antiviral spectrum and underlying mechanism of how these proteins exert antiviral function were reviewed.
Interferon-induced transmembrane proteins(IFITMs), a class of novel discovered viral restriction factors, are widely expressed in human tissue cells, mainly located in plasma membrane and endolysosomal comparments, which are the main targets of the virus entry. By inhibiting membrane fusion between virus and cell membrane, IFITMs restrict the entry of a broad spectrum of viruses, including Ebola virus, influenza A virus, severe acute respiratory syndromes(SARS) coronavirus, dengue virus, West Nile virus and Zika virus. Although IFITM has been shown to be able to suppress the infection of virus of the eight virus families, and it primarily inhibits the fusion process of the virus entry stage, but the mechanism of IFITM antiviral activity remains unknown. In recent years, the antiviral effect of IFITM and its mechanism has become a hotspot in related fields. Here the recent advance of IFITM's antiviral spectrum and underlying mechanism of how these proteins exert antiviral function were reviewed.
引文
[1]Hickford D,Frankenberg S,Shaw G,etal.Evolution of vertebrate interferon inducible transmembrane proteins[J].BMC Genomics,2012,13(1):155.
[2]Smith SE,Weston S,Kellam P,et al.IFITM proteins-cellular inhibitors of viral entry[J].Curr Opin Virol,2014,4(2):71-77.
[3]Bailey CC,Kondur HR,Huang I,et al.Interferon-induced transmembrane protein 3 is a typeⅡtransmembrane protein[J].J Biol Chem,2013,288(45):32184-32193.
[4]John SP,Chin CR,Perreira JM,et al.The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication[J].J Virol,2013,87(14):7837-7852.
[5]Feeley EM,Sims JS,John SP,et al.IFITM3 inhibits influenza A virus infection by preventing cytosolic entry[J].PLo S Pathog,2011,7(10):e1002337.
[6]Amini-Bavil-Olyaee S,Choi YJ,Lee JH,et al.The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry[J].Cell Host Microbe,2013,13(4):452-464.
[7]Zhao X,Guo F,Liu F,et al.Interferon induction of IFITM proteins promotes infection by human coronavirus OC43[J].Proc Nat I Acad Sci USA,2014,111(18):6756-6761.
[8]Diamond MS,Farzan M.The broad-spectrum antiviral functions of IFIT and IFITM proteins[J].Nat Rev Immunol,2013,13(1):46-57.
[9]Gerlach T,Hensen L,Matrosovich T,et al.Ph-optimum of hemagglutinin-mediated membrane fusion determines sensitivity of influenza A viruses to the interferon-induced antiviral state and IFITMs[J].J Virol,2017,91(11):e00246-17.
[10]Brass AL,Huang IC,Benita Y,et al.The IFITM proteins mediate cellular resistance to influenza A H1N1 virus,West Nile virus,and dengue virus[J].Cell,2009,139(7):1243-1254.
[11]Huang IC,Bailey CC,Weyer JL,et al.Distinct patterns of IFITMmediated restriction of filoviruses,SARS coronavirus,and influenza A virus[J].PLo S Pathog,2011,7(1):e1001258.
[12]Lu J,Pan Q,Rong L,et al.The IFITM proteins inhibit HIV-1infection[J].J Virol,2011,85(5):2126-2137.
[13]Schoggins JW,Wilson SJ,Panis M,et al.A diverse range of gene products are effectors of the typeⅠinterferon antiviral response[J].Nature,2011,472(7344):481-485.
[14]Weidner JM,Jiang D,Pan XB,et al.Interferon-induced cell membrane proteins,IFITM 3 and tetherin,inhibit vesicular stomatitisvirusin fection viadistinct mechanisms[J].J Virol,2010,84(24):12646-12657.
[15]Wilkins C,Woodward J,Lau D T,et al.IFITM1 is a tight junction protein that inhibits hepatitis C virus entry[J].Hepatology,2013,57(2):461-469.
[16]Chan YK,Huang IC,and Farzan M.IFITM proteins restrict antibody-dependent enhancement of dengue virus infection[J].PLo S One,2012,7(3):e34508.
[17]Anafu AA,Bowen CH,Chin CR,et al.Interferon-inducible transmembrane protein 3(IFITM3)restricts reovirus cell entry[J].J Biol Chem,2013,288(24):17261-17271.
[18]Rabbani MA,Ribaudo M,Guo JT,et al.Identification of interferonstimulated gene proteins that inhibit human parainfluenza virus type3[J].J Virol,2016,90(24):11145-11156.
[19]Foster T,Wilson H,Iyer S,et al.Resistance of transmitted founder HIV-1 to IFITM-mediated restriction[J].Cell Host Microbe,2016,20(4):429-442.
[20]Yount JS,Moltedo B,Yang YY,et al.Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3[J].Nat Chem Biol,2010,6(8):610-614.
[21]Yount JS,Karssemeijer RA,and Hang HC.S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3(IFITM3)-mediated resistance to influenza virus[J].J Biol Chemy,2012,287(23):19631-19641.
[22]Li K,Markosyan RM,Zheng YM,et al.IFITM proteins restrict viral membrane hemifusion[J].PLo S Pathog,2013,9(1):e1003124.
[23]Jia R,Pan Q,Ding S,et al.The N-terminal region of IFITM3modulates its antiviral activity by regulating IFITM3 cellular localization[J].J Virol,2012,86(24):13697-13707.
[24]Everitt AR,Clare S,Pertel T,et al.IFITM3 restricts the morbidity and mortality associated with influenza[J].Nature,2012,484(7395):519-523.
[25]Zhang YH,Zhao Y,Li N,et al.Interferon-induced transmembrane protein-3 genetic variant rs12252-c is associated with severe influenza in chinese individuals[J].Nat Commun,2011,4(1):1418.
[26]Fu B,Wang L,Li S,et al.ZMPSTE24 defends against influenza and other pathogenic viruses[J].J Exp Med,2017,214(4):919-929.
[2]Smith SE,Weston S,Kellam P,et al.IFITM proteins-cellular inhibitors of viral entry[J].Curr Opin Virol,2014,4(2):71-77.
[3]Bailey CC,Kondur HR,Huang I,et al.Interferon-induced transmembrane protein 3 is a typeⅡtransmembrane protein[J].J Biol Chem,2013,288(45):32184-32193.
[4]John SP,Chin CR,Perreira JM,et al.The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication[J].J Virol,2013,87(14):7837-7852.
[5]Feeley EM,Sims JS,John SP,et al.IFITM3 inhibits influenza A virus infection by preventing cytosolic entry[J].PLo S Pathog,2011,7(10):e1002337.
[6]Amini-Bavil-Olyaee S,Choi YJ,Lee JH,et al.The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry[J].Cell Host Microbe,2013,13(4):452-464.
[7]Zhao X,Guo F,Liu F,et al.Interferon induction of IFITM proteins promotes infection by human coronavirus OC43[J].Proc Nat I Acad Sci USA,2014,111(18):6756-6761.
[8]Diamond MS,Farzan M.The broad-spectrum antiviral functions of IFIT and IFITM proteins[J].Nat Rev Immunol,2013,13(1):46-57.
[9]Gerlach T,Hensen L,Matrosovich T,et al.Ph-optimum of hemagglutinin-mediated membrane fusion determines sensitivity of influenza A viruses to the interferon-induced antiviral state and IFITMs[J].J Virol,2017,91(11):e00246-17.
[10]Brass AL,Huang IC,Benita Y,et al.The IFITM proteins mediate cellular resistance to influenza A H1N1 virus,West Nile virus,and dengue virus[J].Cell,2009,139(7):1243-1254.
[11]Huang IC,Bailey CC,Weyer JL,et al.Distinct patterns of IFITMmediated restriction of filoviruses,SARS coronavirus,and influenza A virus[J].PLo S Pathog,2011,7(1):e1001258.
[12]Lu J,Pan Q,Rong L,et al.The IFITM proteins inhibit HIV-1infection[J].J Virol,2011,85(5):2126-2137.
[13]Schoggins JW,Wilson SJ,Panis M,et al.A diverse range of gene products are effectors of the typeⅠinterferon antiviral response[J].Nature,2011,472(7344):481-485.
[14]Weidner JM,Jiang D,Pan XB,et al.Interferon-induced cell membrane proteins,IFITM 3 and tetherin,inhibit vesicular stomatitisvirusin fection viadistinct mechanisms[J].J Virol,2010,84(24):12646-12657.
[15]Wilkins C,Woodward J,Lau D T,et al.IFITM1 is a tight junction protein that inhibits hepatitis C virus entry[J].Hepatology,2013,57(2):461-469.
[16]Chan YK,Huang IC,and Farzan M.IFITM proteins restrict antibody-dependent enhancement of dengue virus infection[J].PLo S One,2012,7(3):e34508.
[17]Anafu AA,Bowen CH,Chin CR,et al.Interferon-inducible transmembrane protein 3(IFITM3)restricts reovirus cell entry[J].J Biol Chem,2013,288(24):17261-17271.
[18]Rabbani MA,Ribaudo M,Guo JT,et al.Identification of interferonstimulated gene proteins that inhibit human parainfluenza virus type3[J].J Virol,2016,90(24):11145-11156.
[19]Foster T,Wilson H,Iyer S,et al.Resistance of transmitted founder HIV-1 to IFITM-mediated restriction[J].Cell Host Microbe,2016,20(4):429-442.
[20]Yount JS,Moltedo B,Yang YY,et al.Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3[J].Nat Chem Biol,2010,6(8):610-614.
[21]Yount JS,Karssemeijer RA,and Hang HC.S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3(IFITM3)-mediated resistance to influenza virus[J].J Biol Chemy,2012,287(23):19631-19641.
[22]Li K,Markosyan RM,Zheng YM,et al.IFITM proteins restrict viral membrane hemifusion[J].PLo S Pathog,2013,9(1):e1003124.
[23]Jia R,Pan Q,Ding S,et al.The N-terminal region of IFITM3modulates its antiviral activity by regulating IFITM3 cellular localization[J].J Virol,2012,86(24):13697-13707.
[24]Everitt AR,Clare S,Pertel T,et al.IFITM3 restricts the morbidity and mortality associated with influenza[J].Nature,2012,484(7395):519-523.
[25]Zhang YH,Zhao Y,Li N,et al.Interferon-induced transmembrane protein-3 genetic variant rs12252-c is associated with severe influenza in chinese individuals[J].Nat Commun,2011,4(1):1418.
[26]Fu B,Wang L,Li S,et al.ZMPSTE24 defends against influenza and other pathogenic viruses[J].J Exp Med,2017,214(4):919-929.