SR-BI Interactome Analysis Reveals a Proviral Role for UGGT1 in Hepatitis C Virus Entry
SR-BI Interactome Analysis Reveals a Proviral Role for UGGT1 in Hepatitis C Virus Entry
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SR-BI 相互作用组分析揭示 UGGT1 在丙型肝炎病毒进入中的前病毒作用
DOI：
10.3389/fmicb.2019.02043
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发表时间：
2019-09-06
影响因子：
5.2
通讯作者：
Zhang, Leiliang
中科院分区：
文献类型：
--
作者：
Huang, Jiazhao;Yin, Han;Zhang, Leiliang
丙型肝炎病毒（HCV）的进入由多种共受体介导，包括清道夫受体B类I型（SR-BI）。为了阐明人SR-BI的相互作用组，我们进行了免疫沉淀（IP）实验结合质谱（MS）分析。UDP-葡萄糖：糖蛋白葡萄糖基转移酶1（UGGT 1）是钙连接蛋白循环中参与蛋白质糖基化的关键组分，被鉴定为SR-BI相互作用蛋白。沉默UGGT 1或N-糖基化抑制剂处理降低SR-BI蛋白水平。进一步的研究表明，人SR-BI在9个天冬酰胺处被N-糖基化。此外，UGGT 1的缺失降低了HCV的进入和感染。有趣的是，沉默SR-BI降低了UGGT 1的蛋白质稳定性和UGGT 1介导的蛋白质质量控制功能。我们的发现不仅确定了UGGT 1作为HCV宿主因子，而且还确定了SR-BI的UGGT 1介导的蛋白质折叠功能。
Hepatitis C virus (HCV) entry is mediated by multiple co-receptors including scavenger receptor class B, type I (SR-BI). To elucidate the interactome of human SR-BI, we performed immunoprecipitation (IP) experiment coupled with mass spectrometry (MS) analysis. UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), a key component of calnexin cycle involved in protein glycosylation, was identified as a SR-BI-interacting protein. Silencing UGGT1 or N-glycosylation inhibitor treatment reduced SR-BI protein level. Further study demonstrated that human SR-BI was N-glycosylated at nine asparagines. Moreover, HCV entry and infection were reduced by the absence of UGGT1. Interestingly, silencing SR-BI reduced protein stability of UGGT1 and protein quality control function mediated by UGGT1. Our finding not only identified UGGT1 as a HCV host factor, but also identified a UGGT1-mediated protein folding function for SR-BI.