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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Viruses are obligate intracellular agents that depend on host cells for successful propagation, hijacking cellular machineries to their own profit. The molecular interplay between host factors and invading viruses is a continuous coevolutionary process that determines viral host range and pathogenesis. The hepatitis C virus (HCV) is a strictly human pathogen, causing chronic liver injuries accompanied by lipid disorders. Upon infection, in addition to protein-protein and protein-RNA interactions usual for such a positive-strand RNA virus, HCV relies on protein-lipid interactions at multiple steps of its life cycle to establish persistent infection, making use of hepatic lipid pathways. This paper focuses on lipoproteins in HCV entry and on receptors and enzymes involved in lipid metabolism that HCV exploits to enter hepatocytes.
"Accordingly, viral interactions with the host's lipid metabolic pathways appear to be essential for the life cycle of HCV. Attachment of the virus to the cell surface LDLR represents the first stage of HCV entry into hepatocytes, and β-lipoproteins influence HCV proliferation [34, 35]. Serum HCV antigen levels are negatively correlated with serum β-lipoprotein levels . "
[Show abstract][Hide abstract] ABSTRACT: It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C.
[Show abstract][Hide abstract] ABSTRACT: An inspection of the sequence similarity between the hepatitis C virus (HCV) polyprotein and human proteins revealed a high level of peptide sharing, with a limited number of motifs unique to the virus (i.e., with no counterpart in the human proteome). Using pentapeptide matching, only 214 motifs out of a total of 3,007 (7.11%) identified HCV as nonself compared to the Homo sapiens proteome. However, this virus-versus-human phenetic difference disappeared at the genetic level. Indeed, a BLAST analysis of pentadecameric oligodeoxynucleotide sequences corresponding to the 214 pentapeptides unique to HCV revealed that almost all of them are present in the human genome, located in the non-coding strand, introns, and/or pseudogenes, thus being, as such, untranslatable. The present data warn against using DNA-based vaccines to fight HCV infection and emphasize peptide uniqueness as the molecular basis for designing effective anti-HCV immunotherapeutic approaches.
Self/Nonself - Immune Recognition and Signaling 04/2011; 2(2):108-113. DOI:10.4161/self.2.2.15795
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