Hepatitis c virus and host cell lipids: An intimate connection

Alvisi, Gualtiero; Madan, Vanesa; Bartenschlager, Ralf

doi:10.4161/rna.8.2.15011

Cited by 138 publications

(129 citation statements)

References 160 publications

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“…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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confidence: 99%

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Characterization of the inhibition of hepatitis C virus entry byIn 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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confidence: 99%

“…3 Three lipid transport molecules on the hepatocyte surface have been implicated in viral entry: Low-density lipoprotein (LDL) receptor mediates cellular uptake of HCV RNA, but may be nonessential for productive infection. 4 Scavenger receptor class B type I (SR-BI) is essential for HCV infection in vitro 5 and is discussed in more detail below.…”

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confidence: 99%

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

et al. 2013

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“…Thus, of intracellular lipid droplets have been associated with the assembly and morphogenesis of DENV and HCV [78,79,146]. Assembly of HCV particles occurs on the surface of lipid droplets and, as mentioned earlier, it is related to the very low density lipoprotein (VLDL) pathway, a phenomenon that leads to the formation of unique lipo-viro-particles [4,147]. The lipoprotein component associated to HCV particles is essential for their infectivity [148], since one of its functions is to interact with LDL-R, thus contributing to viral attachment (section 2.1.1).…”

Section: Lipids and Viral Morphogenesismentioning

confidence: 99%

“…Despite their great diversity, viruses share as a common feature the dependence on host cell factors to complete their replicative cycle. Among the cellular factors required by viruses, lipids play an important role on viral infections [1][2][3][4]. The involvement of lipids in the infectious cycle is shared by enveloped viruses (those viruses whose infectious particle is wrapped by one or more lipid membranes) and non-enveloped viruses [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Among the cellular factors required by viruses, lipids play an important role on viral infections [1][2][3][4]. The involvement of lipids in the infectious cycle is shared by enveloped viruses (those viruses whose infectious particle is wrapped by one or more lipid membranes) and non-enveloped viruses [1][2][3][4]. Apart from taking advantage on cellular lipids that are usually located inside cells, viruses induce global metabolic changes on infected cells, leading to the rearrangement of the lipid metabolism to facilitate viral multiplication [1, [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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