Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry.
Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry.
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DOI：
10.1016/j.celrep.2015.06.063
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发表时间：
2015-08-04
期刊：
影响因子：
8.8
通讯作者：
Pietschmann T
中科院分区：
文献类型：
--
作者：
Gerold G;Meissner F;Bruening J;Welsch K;Perin PM;Baumert TF;Vondran FW;Kaderali L;Marcotrigiano J;Khan AG;Mann M;Rice CM;Pietschmann T
丙型肝炎病毒（HCV）通过多步机制进入人肝细胞，其中涉及病毒受体CD 81等宿主蛋白。CD 81如何控制HCV进入的特征很差，并且病毒结合后的CD 81蛋白相互作用仍然难以捉摸。我们已经开发了一个定量蛋白质组学协议，以确定HCV触发的CD 81相互作用，并发现26个动态结合伙伴。这些蛋白质中至少有六种促进HCV感染，如RNAi所示。我们进一步表征了血清反应因子结合蛋白1（SRFBP 1），该蛋白在HCV摄取期间被募集到CD 81，并支持肝癌细胞和原代人肝细胞中的HCV感染。SRFBP 1促进所有7种HCV基因型的宿主细胞渗透，但不促进水疱性口炎病毒和人冠状病毒的渗透。因此，SRFBP 1是HCV特异性的泛基因型宿主进入因子。这些结果表明，使用定量蛋白质组学来阐明病原体的进入，并强调宿主蛋白质-蛋白质相互作用在HCV入侵的重要性。丙型肝炎病毒结合改变宿主蛋白与受体CD 81的相互作用26种病毒依赖性CD 81相互作用蛋白中的6种促进病毒进入SRFBP 1结合CD 81并有助于所有HCV的感染，但不是VSV，基因型SRFBP 1是膜相关的，并且是HCV进入所需的丙型肝炎病毒（HCV）通过多步机制进入人肝细胞。格罗尔德等人应用定量蛋白质组学来定义负责HCV进入的蛋白质网络，并将SRFBP 1鉴定为病毒受体CD 81的伴侣。
Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion. Hepatitis C virus binding alters host protein interactions with the receptor CD81 Six out of 26 virus-dependent CD81-interacting proteins promote virus entry SRFBP1 binds CD81 and aids infection of all HCV, but not VSV, genotypes SRFBP1 is membrane-associated and required for HCV entry Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism. Gerold et al. apply quantitative proteomics to define the protein network responsible for HCV entry and identify SRFBP1 as a partner for the virus receptor CD81.