Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection

Xie, Na; Huang, Kai; Zhang, Tao; Y, Lei; Li, Rui; Wang, Kui; Zhou, Shengtao; Li, Jingyi; Wu, Jinhua; Wu, Hong; Deng, Cao; Zhao, Xia; Nice, Edouard C.; Huang, Canhua

doi:10.1016/j.jprot.2011.09.011

Cited by 20 publications

(18 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, no association of serum SLs to the viral load of both HBV and HCV patients was determined as well (Table and http://onlinelibrary.wiley.com/doi/10.1002/hep.27587/suppinfo), in line with our previous observations regarding HCV infected patients . This was observed despite the fact that inhibitors of de novo Cer synthesis have been suggested as potent inhibitors of HBV and HCV replication in vitro and despite the involvement of SL‐rich rafts in the life cycle of both HCV and HBV . However, especially in chronic HCV infection, several studies have observed major HCV‐related disruptions of the host (sphingo‐)lipid metabolism, with gene expression of several genes involved in metabolism and transport of SLs, phospholipids, and fatty acids being increased upon HCV infection .…”

Section: Discussionsupporting

confidence: 78%

Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

et al. 2015

View full text Add to dashboard Cite

Ablation of very-long-chain ceramides (Cers) with consecutive elevations in sphinganine levels has been shown to cause a severe hepatopathy in a knockout mouse model. We have recently shown that serum sphingolipids (SLs) are deregulated in patients with chronic liver disease. However, their role as possible biomarkers in liver fibrosis remains to date unexplored. We assessed, using liquid chromatography/tandem mass spectrometry, serum concentrations of various SL metabolites in 406 patients with chronic viral hepatitis, 203 infected with genotype 1 hepatitis C virus (HCV) and 203 with hepatitis B virus (HBV), respectively. We observed significant variations of serum SLs, with sphingosine and sphinganine being, both in univariate (P < 0.05) as well as in multivariate analysis, significantly associated to severity of liver fibrosis in HCV-infected patients (odds ratio [OR]: 1.111; confidence interval [CI]: 1.028-1.202; P 5 0.007 and OR, 0.634; CI, 0.435-0.925; P 5 0.018, respectively). Serum SLs correlated significantly with serum triglyceride and cholesterol levels as well as with insulin resistance, defined by the homeostatic model assessment index, in HCV patients. Sustained viral response rates in HCV patients were independently predicted by serum C24Cer (OR, 0.998; CI, 0.997-0.999; P 5 0.001), its unsaturated derivative C24:1Cer (OR, 1.001; CI, 1.000-1.002; P 5 0.059), and C18:1Cer (OR, 0.973; CI, 0.947-0.999; P 5 0.048), together with ferritin (OR, 1.006; CI, 1.003-1.010; P < 0.001), alkaline phosphatase (OR, 1.020; CI, 1.001-1.039; P 5 0.032), and interleukin-28B genotype (OR, 9.483; CI,; P < 0.001). Conclusion: Our study demonstrates a tight interaction between variations in serum SL levels and progression of liver fibrosis as well as responsiveness to antiviral therapy. Particularly, sphingosine, sphinganine, and C24Cer appear as promising novel biomarkers in chronic HCV infection and should be further evaluated within the noninvasive prediction of liver fibrosis. (HEPATOLOGY 2015;61:812-822)

show abstract

Section: Discussionsupporting

confidence: 78%

Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

et al. 2015

View full text Add to dashboard Cite

show abstract

“…A third unexplored but plausible consequence of TM6SF2 action is influences on viral load in chronic viral hepatitis. Both CHC and CHB are associated with abnormalities in lipid metabolism, (21)(22)(23) lipids play important roles in various aspects of the life cycle of the viruses, (24,25) and we have shown that a variable fraction of hepatitis C virus (HCV) in serum is associated with triglyceride-rich lipoproteins called lipoviral particles that exhibit increased infectivity. (26) Thus, it could be hypothesized that gene variants that modulate hepatic lipid metabolism and TG export could impact on viral load.…”

Section: International Liver Disease Genetics Consortiummentioning

confidence: 99%

Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

et al. 2016

View full text Add to dashboard Cite

A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P 5 0.02) but not different in cohorts with CHC (n 5 2023) and chronic hepatitis B (n 5 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio 5 1.39, 95% confidence interval 1.04-1.87, and odds ratio 5 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. Conclusion: The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (HEPATOLOGY 2016;64:34-46)

show abstract

“…SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments. For instance, Xie et al defined the modification of lipid raft composition in HBV infection ( Xie et al, 2012 ).…”

Section: Quantitative Interaction Proteomics (Interaction Systems Virmentioning

confidence: 99%

Decoding protein networks during virus entry by quantitative proteomics

Bruening

Pietschmann

2016

Virus Research

View full text Add to dashboard Cite

Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein–protein interactions between viral surface proteins and host proteins as well as secondary host protein–protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.

show abstract

Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection

Cited by 20 publications

References 65 publications

Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

Decoding protein networks during virus entry by quantitative proteomics

Contact Info

Product

Resources

About