Abstract
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.
Highlights
Accumulating evidence suggests that cellular lipoprotein components are involved in hepatitis C virus (HCV) morphogenesis, but the precise contribution of these components remains unclear
Since enhancement is specific for HCV glycoproteins and since the sequences of HCV glycoproteins vary widely among genotypes, we determined whether the apolipoprotein C1 (ApoC1) effect is limited to selected genotypes of HCV or whether ApoC1 can broadly enhance the infectivity of HCV pseudotyped particle system (HCVpp) of all six genotypes
We previously reported that high-density lipoprotein (HDL), through its association with ApoC1, was able to enhance infectivity of HCVpp
Summary
Accumulating evidence suggests that cellular lipoprotein components are involved in hepatitis C virus (HCV) morphogenesis, but the precise contribution of these components remains unclear. Assays characterizing the recently developed consensus JFH-1 molecular HCV clone (HCVcc) [19, 33, 35] provided evidence that the infectious particles generated in vitro display sedimentation velocity and buoyant density profiles similar to those described for HCV particles isolated from the plasma samples of HCV-infected patients [15, 16]. Several others have proposed that this enhancement of HCVpp infection involves a complex interplay between the hypervariable region of HCV E2 protein, scavenger receptor class B type I, and HDL [5, 31], even though a direct interaction between HCV envelope proteins and HDL could not be demonstrated [12, 31]
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