Role of N-linked glycans in the interactions of recombinant HCV envelope glycoproteins with cellular receptors.
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-virus 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-receptor 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.
Institute of Biochemical Sciences, National Taiwan University , Taipei, Taiwan.
Po-Chang
PC
Chen
Po-Kai
PK
Chuang
Chein-Hung
CH
Chen
Ya-Ting
YT
Chan
Juine-Ruey
JR
Chen
Sheng-Wei
SW
Lin
Che
C
Ma
Tsui-Ling
TL
Hsu
Chi-Huey
CH
Wong
D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D006031:Glycosylation; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000821:virology*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D011134:Polysaccharides / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human; C433029:CLEC4M protein, human; C087035:E1 protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus