scholarly journals Characterization of Hepatitis C Virus (HCV) and HCV E2 Interactions with CD81 and the Low-Density Lipoprotein Receptor

2000 ◽  
Vol 74 (21) ◽  
pp. 10055-10062 ◽  
Author(s):  
Sabina Wünschmann ◽  
Jheem D. Medh ◽  
Donna Klinzmann ◽  
Warren N. Schmidt ◽  
Jack T. Stapleton
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Confocal Microscopy ◽  
Viral Entry ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protein Synthesis Inhibitor ◽  
Low Density ◽  
E2 Protein ◽  
Intermediate Density

ABSTRACT Hepatitis C virus (HCV) or HCV–low-density lipoprotein (LDL) complexes interact with the LDL receptor (LDLr) and the HCV envelope glycoprotein E2 interacts with CD81 in vitro. However, E2 interactions with LDLr and HCV interactions with CD81 have not been clearly described. Using sucrose gradient-purified low-density particles (1.03 to 1.07 g/cm3), intermediate-density particles (1.12 to 1.18 g/cm3), recombinant E2 protein, or control proteins, we assessed binding to MOLT-4 cells, foreskin fibroblasts, or LDLr-deficient foreskin fibroblasts at 4°C by flow cytometry and confocal microscopy. Viral entry was determined by measuring the coentry of α-sarcin, a protein synthesis inhibitor. We found that low-density HCV particles, but not intermediate-density HCV or controls bound to MOLT-4 cells and fibroblasts expressing the LDLr. Binding correlated with the extent of cellular LDLr expression and was inhibited by LDL but not by soluble CD81. In contrast, E2 binding was independent of LDLr expression and was inhibited by human soluble CD81 but not mouse soluble CD81 or LDL. Based on confocal microscopy, we found that low-density HCV particles and LDL colocalized on the cell surface. The addition of low-density HCV but not intermediate-density HCV particles to MOLT-4 cells allowed coentry of α-sarcin, indicating viral entry. The amount of viral entry also correlated with LDLr expression and was independent of the CD81 expression. Using a solid-phase immunoassay, recombinant E2 protein did not interact with LDL. Our data indicate that E2 binds CD81; however, virus particles utilize LDLr for binding and entry. The specific mechanism by which HCV particles interact with LDL or the LDLr remains unclear.

scholarly journals Infectivity of Hepatitis C Virus Is Influenced by Association with Apolipoprotein E Isoforms

2010 ◽  
Vol 84 (22) ◽  
pp. 12048-12057 ◽  
Author(s):  
Takayuki Hishiki ◽  
Yuko Shimizu ◽  
Reiri Tobita ◽  
Kazuo Sugiyama ◽  
Kazuya Ogawa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Apolipoprotein E ◽  
Culture Medium ◽  
Low Density Lipoprotein ◽  
Ectopic Expression ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Virus Production ◽  
Low Density

ABSTRACT Hepatitis C virus (HCV) is a causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV in circulating blood associates with lipoproteins such as very low density lipoprotein (VLDL) and low-density lipoprotein (LDL). Although these associations suggest that lipoproteins are important for HCV infectivity, the roles of lipoproteins in HCV production and infectivity are not fully understood. To clarify the roles of lipoprotein in the HCV life cycle, we analyzed the effect of apolipoprotein E (ApoE), a component of lipoprotein, on virus production and infectivity. The production of infectious HCV was significantly reduced by the knockdown of ApoE. When an ApoE mutant that fails to be secreted into the culture medium was used, the amount of infectious HCV in the culture medium was dramatically reduced; the infectious HCV accumulated inside these cells, suggesting that infectious HCV must associate with ApoE prior to virus release. We performed rescue experiments in which ApoE isoforms were ectopically expressed in cells depleted of endogenous ApoE. The ectopic expression of the ApoE2 isoform, which has low affinity for the LDL receptor (LDLR), resulted in poor recovery of infectious HCV, whereas the expression of other isoforms, ApoE3 and ApoE4, rescued the production of infectious virus, raising it to an almost normal level. Furthermore, we found that the infectivity of HCV required both the LDLR and scavenger receptor class B, member I (SR-BI), ligands for ApoE. These findings indicate that ApoE is an essential apolipoprotein for HCV infectivity.

scholarly journals Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles

2002 ◽  
Vol 76 (14) ◽  
pp. 6919-6928 ◽  
Author(s):  
P. André ◽  
F. Komurian-Pradel ◽  
S. Deforges ◽  
M. Perret ◽  
J. L. Berland ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Apolipoprotein B ◽  
Core Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hcv Rna ◽  
Low Density ◽  
Density Fractions

ABSTRACT The presence of hepatitis C virus (HCV) RNA-containing particles in the low-density fractions of plasma has been associated with high infectivity. However, the nature of circulating HCV particles and their association with immunoglobulins or lipoproteins as well as the characterization of cell entry have all been subject to conflicting reports. For a better analysis of HCV RNA-containing particles, we quantified HCV RNA in the low-density fractions of plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated chronically HCV-infected patients. HCV RNA was always found in at least one of these fractions and represented 8 to 95% of the total plasma HCV RNA. Surprisingly, immunoglobulins G and M were also found in the low-density fractions and could be used to purify the HCV RNA-containing particles (lipo-viro-particles [LVP]). Purified LVP were rich in triglycerides; contained at least apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical particles with a diameter of more than 100 nm and with internal structures. Delipidation of these particles resulted in capsid-like structures recognized by anti-HCV core protein antibody. Purified LVP efficiently bind and enter hepatocyte cell lines, while serum or whole-density fractions do not. Binding of these particles was competed out by VLDL and LDL from noninfected donors and was blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the LDL receptor increased their internalization. These results suggest that the infectivity of LVP is mediated by endogenous proteins rather than by viral components providing a mechanism of escape from the humoral immune response.

scholarly journals LIPID PROFILE OF CIRRHOTIC PATIENTS AND ITS ASSOCIATION WITH PROGNOSTIC SCORES: a cross-sectional study

2015 ◽  
Vol 52 (3) ◽  
pp. 210-215 ◽  
Author(s):  
Lílian BASSANI ◽  
Sabrina Alves FERNANDES ◽  
Fabiana Viegas RAIMUNDO ◽  
Daniele Lazzarotto HARTER ◽  
Maria Cristina GONZALEZ ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
High Density Lipoprotein ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Hepatitis C Virus Infection

BackgroundIn cirrhosis the production of cholesterol and lipoproteins is altered.ObjectiveEvaluate the lipid profile by measuring total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and triglyceride levels in patients with cirrhosis caused by alcoholism and/or hepatitis C virus infection and determine its association with Child-Pugh and MELD scores.MethodsCross-sectional retrospective study of patients treated at the outpatient clinic in Porto Alegre, Brazil, from 2006 to 2010.ResultsIn total, 314 records were reviewed, and 153 (48.7%) met the inclusion criteria, of which 82 (53.6%) had cirrhosis that was due to hepatitis C virus infection, 50 (32.7%) were due to alcoholism, and 21 (13.7%) were due to alcoholism and hepatitis C virus infection. The total cholesterol levels diminished with a Child-Pugh progression (P<0.001). Child-Pugh C was significantly associated with lover levels of low-density lipoprotein (<70 mg/dL; P<0.001), high-density lipoprotein (<40 mg/dL; P<0.001) and triglyceride (<70 mg/dL; P=0.003). MELD>20 was associated with lower total cholesterol levels (<100mg/dL; P<0.001), very low-density lipoprotein (<16 mg/dL; P=0.006), and low-density lipoprotein (<70 mg/dL; P=0.003). Inverse and statistically significant correlations were observed between Child-Pugh and all the lipid fractions analyzed (P<0.001). The increase in MELD was inversely correlated with reduced levels intotal cholesterol (P<0.001), high-density lipoprotein (P<0.001), low-density lipoprotein (P<0.001), very low-density lipoprotein (P=0.030) and triglyceride (P=0.003).ConclusionA reduction in the lipid profile in patients with cirrhosis due to hepatitis C virus infection and/or alcoholism was significantly associated with the Child-Pugh and MELD prognostic markers. These results suggest that the lipid profile may be used as a tool to assist in evaluating liver disease.

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