Expression Profiles of Genes Associated With Viral Entry in HCV-Infected Human Liver

Clinical Research Center, Kyushu Medical Center, Fukuoka, Japan.
Journal of Medical Virology (Impact Factor: 2.35). 05/2011; 83(5):921-7. DOI: 10.1002/jmv.22042
Source: PubMed


Recent studies have demonstrated that several cellular factors are involved in entry of hepatitis C virus (HCV) into host cells. Detailed gene expression profiles of these factors in HCV-infected livers have not been reported for humans. Transcriptional levels of LDL receptor (LDLR), CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin genes in liver samples from patients with chronic hepatitis C were investigated. Serum levels of LDL-cholesterol (LDL-C) and HCV core antigen were also evaluated, and expression of claudin-1 and occludin were immunohistochemically analyzed. Compared with normal liver, transcription of LDLR and claudin-1 genes was significantly suppressed (P < 0.0001) and occludin transcription was significantly up-regulated in HCV-infected livers (P < 0.0001). Significant positive correlations were found for LDLR versus occludin, LDLR versus claudin-1, occludin versus claudin-1, and CD81 versus SR-BI in HCV-infected (P = 0.0012, P < 0.0001, P = 0.0004, and P < 0.0001, respectively) and normal livers (P < 0.0001, P = 0.0051, P < 0.0001, and P < 0.0001, respectively). Positive correlation was observed between serum levels of HCV core antigen and LDL-C (P = 0.0147), with their levels negatively correlated to LDLR (P = 0.0270 and P = 0.0021, respectively). Immunohistochemically, hepatocellular expression of claudin-1 and occludin was increased in HCV-infected livers. Different levels of expression were demonstrated at the mRNA and protein levels for occludin and claudin-1 in HCV-infected and normal livers. Correlation of elements associated with viral entry was comparable in HCV-infected and normal livers.

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    • "Studying the expression profiles of genes involved in lipid metabolism and HCV entry in liver biopsies from HCV-infected patients with chronic hepatitis C, the group of Enjoji revealed that LDL-R gene expression was significantly suppressed in HCV-infected compared with normal liver, and inversely correlated to the serum content of LDL-associated cholesterol and HCV core protein [67, 68]. Interestingly, a positive correlation between LDL-R and SR-BI gene expression was observed only in HCV-infected livers. "
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