Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps

Thi, Viet Loan Dao; Granier, Christelle; Zeisel, Mirjam B.; Guérin, Maryse; Mancip, Jimmy; Granio, Ophélia; Pénin, François; Lavillette, Dimitri; Bartenschlager, Ralf; Baumert, Thomas F.; Cosset, François‐Loïc; Dreux, Marlène

doi:10.1074/jbc.m112.365924

Cited by 110 publications

(123 citation statements)

References 95 publications

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“…Of note, their major difference-G451R, but not DHVR1, directly bind SR-BI-has been shown only with sE2, but not complete virions. 35,36 Given that SR-BI is thought to act at more than one step of the HCV-entry process, 21,22 further work will clearly be needed to define the exact effects of the different viral variants and inhibitors of the virus-SR-BI interactions. In addition, it is interesting to speculate how oxidative modification of apolipoproteins, such as ApoE and ApoC1, currently known to be associated with HCV, would affect HCV infectivity.…”

Section: Discussionmentioning

confidence: 99%

“…20 Recent work has suggested that SR-BI fulfils at least two distinct functions during viral entry: one related to initial attachment and another during post-binding. 5,21,22 Among SR-BI ligands, HDL has a modest enhancing effect on HCV entry, 23 whereas oxLDL has been found to be a strong inhibitor. 24 oxLDL is a modified form of LDL that is generated early on in the pathogenesis of atherosclerosis, when native LDL deposited in early atherosclerotic lesions (''fatty streaks'') undergoes oxidative modifications.…”

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confidence: 99%

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Characterization of the inhibition of hepatitis C virus entry by In vitro –generated and patient-derived oxidized low-density lipoprotein

et al. 2013

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Oxidized low-density lipoprotein (oxLDL) has been reported as an inhibitor of hepatitis C virus (HCV) cell entry, making it the only known component of human lipid metabolism with an antiviral effect on HCV. However, several questions remain open, including its effect on full-length cell-culture-grown HCV (HCVcc) of different genotypes or on other steps of the viral replication cycle, its mechanism of action, and whether endogenous oxLDL shares the anti-HCV properties of in vitro-generated oxLDL. We combined molecular virology tools with oxLDL serum measurements in different patient cohorts to address these questions. We found that oxLDL inhibits HCVcc at least as potently as HCV pseudoparticles. There was moderate variation between genotypes, with genotype 4 appearing the most oxLDL sensitive. Intracellular RNA replication and assembly and release of new particles were unaffected. HCV particles entering target cells lost oxLDL sensitivity with time kinetics parallel to anti-SR-BI (scavenger receptor class B type I), but significantly earlier than anti-CD81, suggesting that oxLDL acts by perturbing interaction between HCV and SR-BI. Finally, in chronically HCV-infected individuals, endogenous serum oxLDL levels did not correlate with viral load, but in HCV-negative sera, high endogenous oxLDL had a negative effect on HCV infectivity in vitro. Conclusion: oxLDL is a potent pangenotype HCV entry inhibitor that maintains its activity in the context of human serum and targets an early step of HCV entry. (HEPATOLOGY 2013;57:1716-1724 C hronic hepatitis C virus (HCV) infection affects an estimated 160 million people worldwide. 1 Chronic HCV is a frequent cause of end-stageliver diseases (ESLDs) and hepatocellular carcinoma as well as a common indication for liver transplantation (LT). Treatment remains problematic because of side effects and high cost. A particular problem is graft reinfection that occurs immediately after LT for HCVassociated ESLD and often leads to transplant hepatitis and graft loss. 2 The HCV replication cycle is intricately linked to host lipid metabolism. 3 The production of infectious viral particles is dependent on the cellular very-lowdensity lipoprotein (VLDL) assembly machinery, and

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Characterization of the inhibition of hepatitis C virus entry by In vitro –generated and patient-derived oxidized low-density lipoprotein

et al. 2013

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“…The horizontal bars represent the median values. HCVfrg, n ϭ 9; HCVcc, n ϭ 3. apoE function, our findings suggested that apoE is an essential factor for entry of infectious in vivo produced virus (23,(42)(43)(44)(45)(46).…”

Section: Hcvfrg Infectious Particles Have a Lower Density As Comparedmentioning

confidence: 92%

“…Finally, presumably at a further step of entry, HCVcc particles of lower-intermediate density (i.e. 1.08 -1.13 g/ml) and HCV pseudoparticles become able to bind SR-BI via a direct interaction with the E2 glycoprotein, which results in enhancement of their entry process (23)(24)(25).…”

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confidence: 99%

“…Moreover, other proteins implicated in cholesterol uptake such as Niemann Pick C-1-like 1 (21), and host cell kinases such as the epidermal growth factor receptor and the ephrin receptor A2 (22) have been identified as cofactors of HCV entry. Using the HCVcc and HCV pseudoparticle models, our laboratory recently demonstrated that SR-BI mediates entry of particles independently of their density via its capacity to transfer lipids to and from different carriers (23,24). Finally, presumably at a further step of entry, HCVcc particles of lower-intermediate density (i.e.…”

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Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

Calattini¹,

Fusil²,

Mancip³

et al. 2015

Journal of Biological Chemistry

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Background:We compared viral subpopulations derived from humanized liver mouse model versus cell culture. Results:In vivo and in vitro produced particles show different biophysical properties and receptor usage. Conclusion:In vivo models allow functional investigations on how lipid metabolism and hepatic environment influence HCV entry. Significance: HCV produced from humanized liver mice may better reflect the characteristics of virus from HCV-infected patients.

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Tracking Hepatitis C Virus Interactions with the Hepatic Lipid Metabolism

Vièyres

Pietschmann

2020

The Liver

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Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps

Cited by 110 publications

References 95 publications

Characterization of the inhibition of hepatitis C virus entry by In vitro –generated and patient-derived oxidized low-density lipoprotein

Characterization of the inhibition of hepatitis C virus entry by In vitro –generated and patient-derived oxidized low-density lipoprotein

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

Tracking Hepatitis C Virus Interactions with the Hepatic Lipid Metabolism

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