Role of N-Linked Glycans in the Interactions of Recombinant HCV Envelope Glycoproteins with Cellular Receptors

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• 作者：Po-Chang Chen ; Po-Kai Chuang ; Chein-Hung Chen ; Ya-Ting Chan ; Juine-Ruey Chen ; Sheng-Wei Lin ; Che Ma ; Tsui-Ling Hsu ; Chi-Huey Wong
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：July 18, 2014
• 年：2014
• 卷：9
• 期：7
• 页码：1437-1443
• 全文大小：322K
• ISSN：1554-8937

文摘

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis and hepatocellular carcinoma. It infects human liver cells through several cellular protein receptors including CD81, SR-BI, claudin-1, and occludin. Previous reports also show that lectin receptors can mediate HCV recognition and entry. The envelope proteins of HCV (E1 and E2) are heavily glycosylated, further indicating the possible roles of lectin receptor鈥搗irus interaction in HCV infection. However, there is limited study investigating the relationship of HCV envelope glycoproteins and lectin as well as non-lectin receptors. Here we used surface plasmon resonance to examine the binding affinity of different glycoforms of recombinant HCV envelope protein to receptors and inspected the infectivity and assembly of HCV pseudoparticles composed of different glycoforms of envelope proteins. Our results indicated that DC-SIGN, L-SIGN, and Langerin had higher affinity to recombinant HCV envelope proteins in the presence of calcium ions than non-lectin receptors, and envelope proteins with Man8/9 N-glycans showed approximate 10-fold better binding to lectin receptors than envelope proteins with Man5 and complex type N-glycans. Interestingly, comparing among glycoforms, recombinant envelope proteins with Man5 N-glycans showed the highest binding affinity when interacting with non-lectin receptors. In summary, the glycans on HCV envelope protein play a modulatory role in HCV assembly and infection and direct HCV鈥搑eceptor interaction, which mediates viral entry in different cells. Receptors with high affinity to HCV envelope proteins may be considered as targets for development of a therapeutic strategy against HCV.