Apolipoprotein c1 association with hepatitis C virus.
Accumulating evidence suggests that cellular lipoprotein components are involved in hepatitis C virus (HCV) morphogenesis, but the precise contribution of these components remains unclear. We investigated the involvement of apolipoprotein C1 (ApoC1) in HCV infection in the HCV pseudotyped particle system (HCVpp), in the recently developed cell culture infection model (HCVcc), and in authentic HCV isolated from viremic chimpanzees. Viral genomes associated with HCVcc or authentic HCV were efficiently immunoprecipitated by anti-ApoC1, demonstrating that ApoC1 was a normal component of HCV. The infectivities of HCVpp that had been mixed with ApoC1 and, more importantly, untreated HCVcc collected from lysates or media of infected Huh7.5 cells were directly neutralized by anti-ApoC1. Indeed, convalescent anti-HCV immunoglobulin G and anti-ApoC1 each neutralized over 75% of infectious HCVcc particles, indicating that many, if not all, infectious particles were recognized by both antibodies. Moreover, peptides corresponding to the C-terminal region of ApoC1 blocked infectivity of both HCVpp and HCVcc. Altogether, these results suggest that ApoC1 associates intracellularly via its C-terminal region with surface components of virions during viral morphogenesis and may play a major role in the replication cycle of HCV.
Meunier
Jean-Christophe
JC
Viral Envelopes and Retrovirus Engineering, Human Virology Department, INSERM U758, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France. jean-christophe.meunier@ens-lyon.fr
Russell
Rodney S
RS
Engle
Ronald E
RE
Faulk
Kristina N
KN
Purcell
Robert H
RH
Emerson
Suzanne U
SU
D000818:Animals; D053302:Apolipoprotein C-I / Q000378:metabolism*; D002460:Cell Line; D002469:Cell Separation; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016679:Genome, Viral; D006023:Glycoproteins / Q000737:chemistry; D016174:Hepacivirus / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D053302:Apolipoprotein C-I; D006023:Glycoproteins; D019812:Heparan Sulfate Proteoglycans; D007074:Immunoglobulin G; D008074:Lipoproteins