HCV and lipoproteins: Is oxLDL an Achilles' heel of the Trojan horse?

Dreux, Marlène; Cosset, François‐Loïc

doi:10.1002/hep.21202

Cited by 4 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to some, a 'Trojan horse' mechanism could be used by HCV to facilitate its entry into the CNS. 41 HCV-infected peripheral blood mononuclear cells may enter the CNS and interact with brain cells, especially astrocytes. 42 In the present study it was found that PN was more frequent among HCV-infected individuals than among HTLV-1-infected patients.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus and human T-cell lymphotropic virus type 1 co-infection: impact on liver disease, virological markers, and neurological outcomes

Espíndola

Vizzoni

Lampe

et al. 2017

International Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus and human T-cell lymphotropic virus type 1 co-infection: impact on liver disease, virological markers, and neurological outcomes

Espíndola

Vizzoni

Lampe

et al. 2017

International Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…With evidence from in vitro work supporting several possible mechanisms involving serum lipoproteins, cholesterol metabolism, lipoprotein receptors, and HCV entry, replication and secretion, the significant relationships between both baseline and changes from baseline LDLc and TG levels and rates of SVR are biologically feasible 15‐22, 26‐30. The direct relationship between LDLc and SVR may partially be explained by competition for LDL receptor sites preventing viral entry into hepatocytes, increasing exposure of HCV to the host immune response in the serum.…”

Section: Discussionmentioning

confidence: 99%

“…Observations from in vitro studies suggest relationships between lipoproteins and HCV that are important for mechanisms of viral entry into hepatocytes, viral replication, and secretion. Several studies suggest that HCV may combine with lipoproteins in the serum, possibly obscuring the virus from the host immune response, which may in turn help in viral entry into the hepatocytes 15‐18. Various receptors involved in lipoprotein‐viral particle entry into hepatocytes are posited, including the scavenger receptor B1 (SR‐B1) and LDL receptor 19‐22.…”

mentioning

confidence: 99%

Associations Between Serum Lipids and Hepatitis C Antiviral Treatment Efficacy†,‡

Ramcharran¹,

Wahed²,

Conjeevaram³

et al. 2010

Hepatology

View full text Add to dashboard Cite

Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR. Conclusion: Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication. (HEPATOLOGY 2010;52:854-863)

show abstract

The Exchangeable Apolipoprotein ApoC-I Promotes Membrane Fusion of Hepatitis C Virus

Dreux

Boson

Ricard‐Blum

et al. 2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cell entry of hepatitis C virus (HCV) is strikingly linked to lipoproteins and their receptors. Particularly, high density lipoprotein (HDL) enhances infectivity of HCV by involving the lipid-transfer function of the scavenger receptor BI, a receptor for both HDL and HCV. Here, we demonstrate that apoC-I, an exchangeable apolipoprotein that predominantly resides in HDL, specifically enhances HCVcc and HCVpp infectivity and increases the fusion rates between viral and target membranes via a direct interaction with the HCV surface. We identify the hypervariable region 1, located at the N terminus of the HCV E2 glycoprotein, as an essential viral component that modulates apoC-I-mediated enhancement of HCV fusion properties. The affinity of apoC-I for the HCV membrane may predispose it for fusion with a target membrane via alterations of its outer phospholipid layer. Conversely, we found that excess apoC-I provided as lipoprotein-free protein induces the disruption of the HCV membrane and subsequent loss of infectivity. Furthermore, our data indicate that HDL neither interacts nor spontaneously exchanges apoC-I with HCV virions. Because apoC-I is not present in serum as a lipoprotein-free form, our results suggest that HDL-embedded apoC-I could be released from the lipoprotein particle through a fine-tuned mechanism regulated via a triple interplay between hypervariable region 1, HDL, and scavenger receptor BI, resulting in optimal apoC-I recruitment on the viral membrane. These results provide the first description of a host serum factor helping the fusion process of an enveloped virus. With an estimated 170 million infected individuals, hepatitis C virus (HCV)4 has a major impact on public health (2).HCV is an enveloped, positive-stranded RNA virus of the Flaviviridae family. Its genome encodes a single polyprotein processed by viral and cellular proteases into three structural (core, E1 and E2 glycoproteins) and seven non-structural proteins (3, 4). For a long time the study of HCV cell entry has remained limited because the ex vivo characterization of HCV derived from plasma has proven extremely difficult. This is due in large part to the low infectivity of the virus in cultures of primary hepatocytes, to its high genetic heterogeneity, and to its association through different forms with lipoproteins. Thus, to overcome these severe limitations toward the molecular characterization of HCV infection, several surrogate assays have been developed. Two relevant and complementary in vitro cell entry assays consist of cell culture-grown genuine HCV (HCVcc) derived from a fulminant hepatitis C, JFH-1 (5-7), and of HCV pseudo-particles (HCVpp) harboring authentic E1E2 glycoproteins, which are particularly amenable to mutagenesis analysis (8 -10). Although HCVcc further permit investigation of the late infection steps, HCVpp, which can be produced in nonhepatic cells that can be readily complemented with hepatic factors, offers a particularly flexible plate form to study the structure/function relationship of HCV glycopro...

show abstract

HCV and lipoproteins: Is oxLDL an Achilles' heel of the Trojan horse?

Cited by 4 publications

References 26 publications

Hepatitis C virus and human T-cell lymphotropic virus type 1 co-infection: impact on liver disease, virological markers, and neurological outcomes

Hepatitis C virus and human T-cell lymphotropic virus type 1 co-infection: impact on liver disease, virological markers, and neurological outcomes

Associations Between Serum Lipids and Hepatitis C Antiviral Treatment Efficacy†,‡

The Exchangeable Apolipoprotein ApoC-I Promotes Membrane Fusion of Hepatitis C Virus

Contact Info

Product

Resources

About