A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles.
Hepatitis C virus (HCV) infection is a major worldwide health problem. Our previous results showed that HCV evolved to gain the enhanced infectivity and altered buoyant density distribution during persistent infections in vitro. Here we showed that a point mutation I414T in HCV E2 was mainly responsible for these phenotypic changes. While the I414T mutation had no significant effect on HCV RNA replication and viral entry, it enhanced the production of infectious viral particles and decreased the dependency of viral entry on the levels of HCV receptors. Furthermore, we showed that the I414T mutation reduced the association of viral particles with low-density lipoprotein or very low-density lipoproteins during the virus secretion process, and the infection of the delipidated virus was more sensitive to the blockade by an anti-E2 neutralizing antibody and recombinant CD81 proteins. Our results provided more insights into understanding the roles of lipoprotein associations in HCV life cycle.
Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai, China.
Wanyin
W
Tao
Chunliang
C
Xu
Qiang
Q
Ding
Rui
R
Li
Yu
Y
Xiang
Josan
J
Chung
Jin
J
Zhong
D057134:Antibodies, Neutralizing / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D017354:Point Mutation; D012367:RNA, Viral / Q000378:metabolism; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000235:genetics*; D014771:Virion / Q000472:pathogenicity / Q000502:physiology; D053586:Virus Internalization
D057134:Antibodies, Neutralizing; D015703:Antigens, CD; C554798:CD81 protein, human; D008077:Lipoproteins, LDL; D012367:RNA, Viral; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus