High‐density lipoprotein binding rate differs greatly between genotypes 1b and 2a/2b of hepatitis C virus

Abstract

The hepatitis C virus (HCV) virion is associated with lipoproteins and immunoglobulins in the sera of patients with chronic hepatitis C; however, an accurate binding rate of HCV to lipoproteins or immunoglobulins has not yet been elucidated. Therefore, the accurate binding rate of HCV to low-density lipoproteins (LDL), high-density lipoproteins (HDL), and immunoglobulins was measured quantitatively by a real-time PCR assay. The immunoglobulin binding rate of HCV was found to be greater than 97.5% in most patients, as compared with an LDL binding rate of greater than 80% in most patients. In contrast, the HDL binding rate was greater than 98% in the genotype 2a/2b patients, while it varied in the genotype 1b patients. The genotype 2a/2b HCV not only had a higher LDL binding rate but also had a strikingly higher HDL binding rate than that of the genotype 1b HCV. These lipoprotein binding rates correlated neither to any patient's variables, including the serum apolipoprotein levels, nor to the viral load or the hypervariable region 1 (HVR 1) amino acid sequences. Most of the HCV virions in the sera of such patients have been shown to be associated simultaneously with immunoglobulins and LDL and/or HDL, but not exclusively.

Apolipoprotein E Codetermines Tissue Tropism of Hepatitis C Virus and Is Crucial for Viral Cell-to-Cell Transmission by Contributing to a Postenvelopment Step of Assembly

“…Serumderived HCV was reported to associate with various lipoproteins, including ApoAI, -B, -C1, and -E (26,27,29), which is thought to influence particle properties with regard to density, neutralization by antibodies, and receptor interactions. Given that Huh-7.5 cells secrete both ApoE and ApoB and express ApoC1 mRNA, we hypothesized that HCV particles produced in these cells may carry a different spectrum of lipoproteins than those released from 293T/miR-122/ApoE cells (and thus in the absence of detectable ApoB and ApoC1).…”

“…HCV particles display an unusually variable and generally low buoyant density, which is due to the tight interaction of HCV particles with lipoproteins (25)(26)(27). Congruently, assessment of the composition of serum-derived HCV revealed the presence of several apolipoproteins, including apolipoprotein AI (ApoAI), ApoB, ApoC1, and ApoE (26)(27)(28)(29). In parallel, several studies have highlighted the involvement of numerous host factors for production of infectious HCV particles (summarized in reference 30).…”

Hepatitis C virus RNA localization in human carotid plaques

“…29 The predominance of HCV genotype 2 we observed in atherosclerotic patients is potentially interesting, as this genotype seems to be more closely associated with lipoproteins than other genotypes. 30 However, further studies involving larger populations are needed to confirm this hypothesis. The present study does not provide information about the mechanisms involved in the infection of plaque tissue.…”

Human Serum Facilitates Hepatitis C Virus Infection, and Neutralizing Responses Inversely Correlate with Viral Replication Kinetics at the Acute Phase of Hepatitis C Virus Infection

“…The second, at a density of Ͻ1.06, contains viral particles that are mostly lipoprotein associated and infectious. The amount of HCV RNA in these fractions is highly variable and depends on the disease stage (60) and on the virus genotype (29). Whether the association of HCVpp with such serum components may occur in vitro upon their incubation with human serum and subsequently facilitate infection warrants further investigation.…”