干扰素诱导跨膜蛋白抗病毒机制研究进展

doi:10.3877/cma.j.issn.1674-1358.2018.03.002

中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (03) : 212 -215. doi: 10.3877/cma.j.issn.1674-1358.2018.03.002

所属专题：文献；

综述

干扰素诱导跨膜蛋白抗病毒机制研究进展

侯志飞¹, 赵学森¹^,^†(

)

^1. 100015　北京，首都医科大学附属北京地坛医院传染病研究所

收稿日期:2017-07-10 出版日期:2018-06-15
通信作者: 赵学森
基金资助:
国家自然科学基金(No. 81571976)

Advances in antiviral study on interferon-induced transmembrane protein

Zhifei Hou¹, Xuesen Zhao¹^,^†()

^1. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Received:2017-07-10 Published:2018-06-15
Corresponding author: Xuesen Zhao
About author:
Corresponding author: Zhao Xuesen, Email: zhaoxuesen@ccmu.edu.cn

全文 ( ) 下载PDF ( ) 导出引用

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。

关键词: 干扰素诱导跨膜蛋白, 病毒侵入, 膜融合

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.

Key words: Interferon-induced transmembraneprotein, Viral entry, Membrane fusion

图1 IFITM1/2/3的抗病毒机制

表1 IFITM1/2/3抗病毒谱及其机制

基因名称	诱导类型	细胞定位	主要表达细胞	作用机制	抑制主要病毒	促进病毒
IFITM1	Ⅰ型IFN、Ⅱ型IFN	细胞膜	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	HCV、PIV3、SARS-CoV、MARV、EBOV、DNV、IAV、HIV、WNV	无
IFITM2	Ⅰ型IFN、Ⅱ型IFN	可能早期内体、晚期内体、溶酶体	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	MERS-CoV、SARS-CoV、VSV、IAV、MARV、EBOV、DNV、WNV、HIV	HCoV-OC43
IFITM3	Ⅰ型IFN、Ⅱ型IFN	早期内体、晚期内体、溶酶体	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	MERS-CoV、SARS-CoV、VSV、IAV、MARV、EBOV、DNV、WNV、HIV	HCoV-OC43

表1 IFITM1/2/3抗病毒谱及其机制

基因名称	诱导类型	细胞定位	主要表达细胞	作用机制	抑制主要病毒	促进病毒
IFITM1	Ⅰ型IFN、Ⅱ型IFN	细胞膜	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	HCV、PIV3、SARS-CoV、MARV、EBOV、DNV、IAV、HIV、WNV	无
IFITM2	Ⅰ型IFN、Ⅱ型IFN	可能早期内体、晚期内体、溶酶体	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	MERS-CoV、SARS-CoV、VSV、IAV、MARV、EBOV、DNV、WNV、HIV	HCoV-OC43
IFITM3	Ⅰ型IFN、Ⅱ型IFN	早期内体、晚期内体、溶酶体	上皮细胞、内皮细胞	抑制病毒与细胞膜融合	MERS-CoV、SARS-CoV、VSV、IAV、MARV、EBOV、DNV、WNV、HIV	HCoV-OC43

[1]	Hickford D, Frankenberg S, Shaw G, et al. 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 type Ⅱ transmembrane 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]. PLoS 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 NatI 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 ifitm-mediated restriction of filoviruses, sars coronavirus, and influenza a virus[J]. PLoS Pathog,2011,7(1):e1001258.
[12]	Lu J, Pan Q, Rong L, et al. The ifitm proteins inhibit hiv-1 infection[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, ifitm3 and tetherin, inhibit vesicular stomatitis virus infection via distinct 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]. PLoS 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 interferon-stimulated gene proteins that inhibit human parainfluenza virus type 3[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]. PLoS Pathog,2013,9(1):e1003124.
[23]	Jia R, Pan Q, Ding S, et al. The n-terminal region of ifitm3 modulates 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.

[1]	侯志飞, 蒋栋, 赵学森, 曾辉. 诱导表达人IFITM3的293细胞株的建立及其对H1N1型流感病毒侵染作用[J]. 中华实验和临床感染病杂志(电子版), 2018, 12(02): 198-203.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Advances in antiviral study on interferon-induced transmembrane protein

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Advances in antiviral study on interferon-induced transmembrane protein