Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.
Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.
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DOI：
10.1371/journal.ppat.1001258
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发表时间：
2011-01-06
期刊：
影响因子：
6.7
通讯作者：
Farzan M
中科院分区：
文献类型：
--
作者：
Huang IC;Bailey CC;Weyer JL;Radoshitzky SR;Becker MM;Chiang JJ;Brass AL;Ahmed AA;Chi X;Dong L;Longobardi LE;Boltz D;Kuhn JH;Elledge SJ;Bavari S;Denison MR;Choe H;Farzan M
干扰素诱导的跨膜蛋白1、2和3 （IFITM1、2和3）是最近发现的抑制甲型流感病毒（IAV）血凝素（HA）蛋白介导的感染的病毒限制因子。本研究表明，IFITM蛋白限制马尔堡病毒和埃博拉丝状病毒（MARV， EBOV）的进入糖蛋白（GP1,2）介导的感染。与这些观察结果一致，干扰素-β特异性地限制了线状病毒和IAV的进入过程。IFITM蛋白还能抑制传染性MARV和EBOV的复制。我们观察到ifitm介导的不同限制模式：与IAV相比，MARV和EBOV的进入过程受到IFITM3的限制较少，但受到IFITM1的限制较多。此外，小鼠Ifitm5和6不限制IAV，但有效抑制丝状病毒的进入。我们进一步证明传染性SARS冠状病毒（SARS- cov）的复制和SARS- cov刺突蛋白介导的进入受到IFITM蛋白的限制。ifitm介导的SARS-CoV的限制性更类似于丝状病毒而不是IAV。胰蛋白酶对受体相关的SARS-CoV假病毒体的治疗绕过了它们对溶酶体组织蛋白酶L的依赖，也绕过了ifitm介导的限制。然而，IFITM蛋白不会降低细胞组织蛋白酶活性或限制病毒粒子进入酸性细胞内区室。我们的数据表明，ifitm介导的限制局限于内吞途径的后期。他们进一步表明，IFITM蛋白以不同的方式限制了广泛的包膜病毒的进入，并独立于病毒受体表达调节细胞的趋向性。细胞表达限制性因子，即主要抑制病毒复制的蛋白质。我们最近描述了一个限制因子家族，干扰素诱导的跨膜（IFITM）蛋白，干扰甲型流感病毒的复制。在病毒成功进入细胞质之前，IFITM蛋白在病毒生命周期的早期独特地抑制复制。本研究表明，几种高致病性病毒（马尔堡病毒、埃博拉病毒和SARS冠状病毒）的进入过程同样被IFITM蛋白破坏。我们比较了IFITM介导的这些病毒与甲型流感病毒的限制性，发现单个IFITM蛋白专门用于限制性。例如，我们描述了两种小鼠IFITM蛋白，它们能有效地限制马尔堡病毒和埃博拉病毒的进入，但不能抑制甲型流感病毒。我们进一步表明，我们可以通过诱导病毒进入质膜或质膜附近的细胞来绕过ifitm介导的限制。这一观察结果表明，限制不是细胞的整体特性，而是局限于晚期内体和溶酶体区室，这是ifitm限制性病毒通常的进入位点。因此，这项研究增强了我们对先天免疫系统如何控制甲型流感病毒和其他致病性病毒的理解。
Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP1,2) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression. Cells express restriction factors, proteins whose primary activity is to inhibit viral replication. We have recently described a family of restriction factors, interferon-inducible transmembrane (IFITM) proteins, that interfere with replication of influenza A virus. The IFITM proteins uniquely inhibit replication early in the viral life-cycle, before the virus can successfully enter the cell cytoplasm. Here we show that the entry processes of several highly pathogenic viruses – Marburg virus, Ebola virus, and SARS coronavirus – are similarly disrupted by IFITM proteins. We compared IFITM-mediated restriction of these viruses with influenza A virus, and discovered that individual IFITM proteins are specialized for restriction. For example, we describe two mouse IFITM proteins that efficiently restrict entry of Marburg and Ebola viruses, but which do not inhibit influenza A virus. We further show that we can circumvent IFITM-mediated restriction by inducing a virus to enter a cell at or near the plasma membrane. This observation indicates that restriction is not a global property of the cell, but rather is localized to late endosomal and lysosomal compartments, the usual entry sites of IFITM-restricted viruses. This study therefore enhances our understanding of how the innate immune system controls influenza A virus and other pathogenic viruses.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
跨膜蛋白的脆弱性干扰素诱导基因家族与小鼠的生殖细胞规范有关。
影响因子：
--
作者：
Lange, U C;Saitou, M;Western, P S;Barton, S C;Surani, M A
通讯作者：
Surani, M A
DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
影响因子：
5.4
作者：
Huang, I-Chueh;Li, Wenhui;Farzan, Michael
通讯作者：
Farzan, Michael
DOI：
10.1073/pnas.0803711105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Chen Chen;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei