Abstract
Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been implicated in several aspects of HCV pathology including oncogenesis and immune subversion. Here we show that expression of the C protein induced specific tyrosine phosphorylation of the TCR-related signaling proteins ZAP-70, LAT and PLC-γ in the T cells. Stable expression of the C protein specifically reduced Src homology domain 2-containing protein tyrosine phosphatase 1 (SHP-1) mRNA and protein accumulation. Quantitative CpG methylation analysis revealed a distinct CpG methylation pattern at the SHP-1 gene promoter in the C protein expressing cells that included specific hypermethylation of the binding site for Sp1 transcription factor. Collectively, our results suggest that HCV may suppress immune responses and facilitate its own persistence by deregulating phosphotyrosine signaling via repressive epigenetic CpG modification at the SHP-1 promoter in the T cells.
Highlights
Hepatitis C virus (HCV) is one of the main causes of liver inflammation in humans.The virus can cause short-term acute infections which are self-limiting and relatively rare
We examined the effects of HCV C protein on phosphotyrosine signaling in T cells
We demonstrate that expression of the HCV C protein induces a particular CpG methylation pattern at the SHP-1 gene promoter
Summary
Hepatitis C virus (HCV) is one of the main causes of liver inflammation in humans. The virus can cause short-term acute infections which are self-limiting and relatively rare. The SHP-1 gene is present on chromosome 12 in humans and contains two different cell-specific promoters. The SHP-1 is a tumor suppressor gene and reduced SHP-1 expression owing to the promoter hypermethylation has been reported in different blood-related cancers [33,34,35,36,37,38,39,40,41]. We demonstrate that expression of the HCV C protein induces a particular CpG methylation pattern at the SHP-1 gene promoter. This epigenetic modification correlates with reduced SHP-1 mRNA expression and general dysregulation of the phosphotyrosine signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
