An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation

Abid, Karim; Pazienza, Valerio; Gottardi, Andrea De; Rubbia‐Brandt, Laura; Conne, Béatrice; Pugnale, Paolo; Rossi, Christine; Mangia, Alessandra; Negro, Francesco

doi:10.1016/j.jhep.2004.12.034

Cited by 153 publications

(136 citation statements)

References 25 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…This effect is relatively modest as compared with the effect of HCV core and the NS4B co-expression system (23-fold). In fact, there is a genotype difference in steatosis induction (46). Because we for an additional 12 h. Cells were harvested and then luciferase activities were determined.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway

Park

Jun

Wakita

et al. 2009

Journal of Biological Chemistry

133

106

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection is often associated with hepatic steatosis and yet the molecular mechanisms of HCVassociated steatosis are poorly understood. Because sterol regulatory element-binding proteins (SREBPs) are the major transcriptional factors in lipogenic gene expression including fatty acid synthase (FAS), we examined the effects of HCV nonstructural proteins on the signaling pathways of SREBP. In this study, we demonstrated that HCV nonstructural 4B (NS4B) protein increased the transcriptional activities of SREBPs. We also showed that HCV NS4B enhanced the protein expression levels of SREBPs and FAS. This was further confirmed in the context of viral RNA replication and HCV infection. The up-regulation of both SREBP and FAS by NS4B protein required phosphatidylinositol 3-kinase activity. We also demonstrated that NS4B protein induced a lipid accumulation in hepatoma cells. In addition, NS4B protein synergistically elevated the transcriptional activity of HCV core-mediated SREBP-1. These results strongly suggest that NS4B may play an important role in HCV-associated liver pathogenesis by modulating the SREBP signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway

Park

Jun

Wakita

et al. 2009

Journal of Biological Chemistry

133

106

View full text Add to dashboard Cite

show abstract

“…31885-023) supplemented with 10% fetal bovine serum, 100 U/ml penicillin, and 100 g/ml streptomycin (all from Invitrogen Life Technologies). We transfected pIRES2-EGFP plasmids containing the HCV 3a or 1b core-encoding region 17 …”

Section: Cell Culture Transfection and Flow Cytometrymentioning

confidence: 99%

“…8,14,15 Given its impact on liver disease progression 8 and response to antivirals, 16 unraveling the interaction between HCV and insulin signaling is of the utmost relevance. We used our model of transient expression of the core protein of different genotypes of HCV 17 to assess the interaction of HCV genotype 3a with the insulin signaling, using as comparison the genotype 1b, for which some data have already been reported. 12 We focused our attention on the IRS-1 and IRS-2 levels and on the mechanisms potentially implicated in their regulation.…”

mentioning

confidence: 99%

The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype‐specific mechanisms†

et al. 2007

Self Cite

View full text Add to dashboard Cite

Both molecular and clinical evidence support a link between HCV infection and insulin resistance. We examined the in vitro interaction between the HCV core protein of genotypes 3a and 1b with the insulin-signaling pathway. We measured the expression levels of insulin receptor substrate 1 (IRS-1), IRS-2, and other factors involved in the insulin signal pathway in a human hepatoma cell line (Huh-7) transiently expressing the HCV core protein of genotypes 3a or 1b by molecular biology and biochemical techniques. The IRS-1 (but not IRS-2) protein level was significantly reduced in Huh-7 expressing the core protein of both genotypes 3a and 1b, as compared to cells transfected with the empty vector. However, while the core protein of genotype 3a promoted IRS-1 degradation through the downregulation of peroxisome proliferator-activated receptor ␥ (PPAR␥) and by upregulating the suppressor of cytokine signal 7 (SOCS-7), the core protein of genotype 1b activated the mammalian target of rapamycin (mTOR). We confirmed these findings by using agonists for PPAR␥ (rosiglitazone) or short interfering RNAs for SOCS-7. Conclusion: Despite the small sequence divergence of the HCV core proteins of genotypes 3a and 1b, the 2 proteins appear to interfere with the insulin signaling pathway using genotype-specific mechanisms.

show abstract

“…Viral steatosis is mostly reported in patients with genotype 3a, in whom fat accumulation correlates with HCV replication levels in serum and liver and disappears after successful antiviral therapy, strongly suggesting a direct role of specific viral products in the fat deposition. To address the role of specific HCV genotype on lipid accumulation in cells, Abid and coworkers [12] developed an in vitro model to study the effect of the core protein belonging to several viral genotypes (1b, 2a, 3a, 3h, 4h and 5a). They concluded that the pattern observed in Huh7 cells upon expression of the six core proteins largely corroborated the phenotype seen in vivo.…”

Section: Pathogenesis Of Steatosis In Hepatitis Cmentioning

confidence: 99%

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

Campo

Romero‐Gómez²

2009

WJG

View full text Add to dashboard Cite

show abstract

An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation

Abstract: Consistent with observations in chronic hepatitis C patients, the in vitro expression of HCV genotype 3a core protein is the ideal candidate model for studying the mechanisms of HCV-associated steatosis.

Cited by 153 publications

References 25 publications

Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway

Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway

The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype‐specific mechanisms†

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

Contact Info

Product

Resources

About