Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production

Lin, Chun Chieh; Tsai, Pei‐Ju; Sun, Hung Yu; Hsu, Mei Chi; Lee, Jin‐Ching; Wu, I‐Chin; Tsao, Chiung Wen; Chang, Ting‐Tsung; Young, Kung-Chia

doi:10.1016/j.jhep.2014.06.026

Cited by 51 publications

(59 citation statements)

References 51 publications

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“…With assistance from microsomal triglyceride transfer protein (MTTP) and its close link to the very-low-density-lipoprotein pathway, HCV virions are assembled as LVPs possessing characteristics similar to those of lipoproteins for their association with apolipoproteins and neutral lipids (8,10,11,32,35). Many apolipoproteins, including apoB, apoE, apoC, apoA-I, and apoJ, were demonstrated to play an important intracellular functional role in HCV LVP assembly and secretion (7,17,(35)(36)(37). Unlike apoB, which remains associated with triglyceride-rich lipoproteins from the beginning of assembly to the end of remnant clearance, exchangeable apolipoproteins (apoE, apoA-I, and apoC) are able to dissociate from and reassociate with lipoprotein particles in circulation (18).…”

Section: Discussionmentioning

confidence: 99%

Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

Yang

Wang

Chi

et al. 2016

J Virol

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Hepatitis C virus (HCV) is a major cause of chronic liver disease, infecting approximately 170 million people worldwide. HCV assembly is tightly associated with the lipoprotein pathway. Exchangeable apolipoprotein E (apoE) is incorporated on infectious HCV virions and is important for infectious HCV virion morphogenesis and entry. Moreover, the virion apoE level is positively correlated with its ability to escape E2 antibody neutralization. However, the role of apoE exchange in the HCV life cycle is unclear. In this study, the relationship between apoE expression and cell permissiveness to HCV infection was assessed by infecting apoE knockdown and derived apoE rescue cell lines with HCV. Exchange of apoE between lipoproteins and HCV lipoviral particles (LVPs) was evaluated by immunoprecipitation, infectivity testing, and viral genome quantification. Cell and heparin column binding assays were applied to determine the attachment efficiency of LVPs with different levels of incorporated apoE. The results showed that cell permissiveness for HCV infection was determined by exogenous apoE-associated lipoproteins. Furthermore, apoE exchange did occur between HCV LVPs and lipoproteins, which was important to maintain a high apoE level on LVPs. Lipid-free apoE was capable of enhancing HCV infectivity for apoE knockdown cells but not apoE rescue cells. A higher apoE level on LVPs conferred more efficient LVP attachment to both the cell surface and heparin beads. This study revealed that exogenous apoE-incorporating lipoproteins from uninfected hepatocytes safeguarded the apoE level of LVPs for more efficient attachment during HCV infection. IMPORTANCEIn this study, a neglected but important role of apoE exchange in HCV LVP infectivity after virus assembly and release was identified. The data indicated that apoE expression level in uninfected cells is important for high permissiveness to HCV infection. Secreted apoE-associated lipoprotein specifically enhances infection of HCV LVPs. apoE exchange between HCV LVP and lipoproteins is important to maintain an adequate apoE level on LVPs for their efficient attachment to cell surface. These data defined for the first time an extracellular role of exchangeable apoE in HCV infection and suggested that exchangeable apolipoproteins reach a natural equilibrium between HCV LVPs and lipoprotein particles, which provides a new perspective to the understanding of the heterogeneity of HCV LVPs in composition. M ore than 170 million people worldwide are infected with hepatitis C virus (HCV). Up to 80% of infected individuals are unable to clear the virus, and persistent infections lead to a high risk of developing liver cirrhosis and hepatocellular carcinoma (1). Direct-acting antivirals (DAA) significantly improved treatment efficiency, but an effective vaccine for the control of new HCV infection is still needed due to the limited access to anti-HCV treatment. Moreover, the emergence of DAA-resistant viruses calls for alternative strategies to control viral breakthrough (2-4).A...

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Section: Discussionmentioning

confidence: 99%

Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

Yang

Wang

Chi

et al. 2016

J Virol

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“…As shown in this study, the DAA regimens of grazoprevir/elbasvir and ledipasvir/sofosbuvir yielded satisfactory treatment responses, as reported previously,38 providing a basis for further investigation of the beneficial effects on lipid homoeostasis with viral clearance. Host cellular lipid metabolism modulates HCV infection and vice versa, indicating that TG and Chol can facilitate HCV genome replication,39 40 whereas VLDL,40 lipid droplets,41 apoB,7 apoE10 and apoJ12 are crucial for the assembly and release of HCV virions. The association of lipoproteins with HCV virions may interfere with lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

Sun

Cheng

Tseng

et al. 2017

Gut

Self Cite

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“…Collectively, change of exchangeable apolipoproteins on the surface of HCV particles could be involved in the efficiency of viral particle formation and morphological characteristics of particles in supernatants or sera. On the other hand, recent report suggested that ApoJ participates in the infection of HCV through the interaction with core and NS5A proteins [69]. Therefore, further studies are needed to clarify the roles of apolipoproteins in the life cycle of HCV.…”

Section: Redundant Role Of the Exchangeable Apolipoproteins In The Fomentioning

confidence: 99%

Roles of Lipoproteins and Apolipoproteins in Particle Formation of Hepatitis C Virus

Fukuhara

Ono

Puig-Basagoiti

et al. 2015

Trends in Microbiology

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Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production

Cited by 51 publications

References 51 publications

Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

Roles of Lipoproteins and Apolipoproteins in Particle Formation of Hepatitis C Virus

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