F protein increases CD4+CD25+ T cell population in patients with chronic hepatitis C

Abstract

HCV is a global health problem with an estimated 230 million chronically infected people worldwide. It has been reported that a 17-kd protein translated from core-encoding genomic region can contribute to immune-mediated mechanisms associated with the development of the chronic disease. Also, Treg cells can be contributed to an inadequate response against the viruses, leading to chronic infection. Here we evaluated the ability of protein F to modulate the frequency of CD4+CD25+FoxP3+T and IL-10+T cells in patients with chronic HCV infection. F gene was amplified and cloned in the expression vector. The protein was purified and used for stimulation of PBMCs in the HCV chronic patients and the control groups. The frequency of CD4+CD25+FoxP3+ T cell-like populations and IL-10-producing CD4+CD25+ T cells was assessed in the HCV-infected patients and in the healthy controls by flow cytometry, which showed an increase of both CD4+CD25+FoxP3+ T cell-like population and IL-10-producing CD4+CD25+ T cells in the HCV-infected patients positive for anti-F antibody. Our results suggest the potential involvement of F and core antigens in increasing the frequency of CD4+CD25+FoxP3+ T cell-like population and IL-10-producing CD4+CD25+ T cells which may be associated with HCV-persistent infection.

Cytokine profile in chronic hepatitis C: An observation

“…Several virus proteins are recognized to have ability to affect signal transduction in immune cells thus influencing effector functions of both innate and adaptive immunity [4][5]. Additionally, chronic activation of immune cells results in exhaustion of immune response [6] and activation of a subgroup of regulatory T cells [7] that contributes to the functional impairment of the virusspecific T cell response. Permanent presence of virus and sustained immune response results in prolonged inflammation and consequential liver injury.…”

A Decline in Anti-Core+1 Antibody Titer Occurs in Successful Treatment of Patients Infected with Hepatitis C Virus

“…The first 10 amino acids of the core+1 protein play a stabilizing role in the conformational structure of the core+1 protein, leading to better folding, rather than acting as an antigenic region (5). Therefore, this homology does not interfere with the anticore+1 positive response (5); besides, the authors' previous study showed no cross-reactivity between the Abs against core+1, truncated core+1, and core proteins (10).…”

“…There are some reports indicating that chronic hepatitis C (CHC) infection is strongly associated with hepatocellular carcinoma (HCC) (3)(4)(5)(6)(7)(8)(9). There is neither effective vaccine for immunization, nor a broadly effective treatment for HCV infection (3).Among different factors associated with chronic HCV infection, alternate reading frame protein (ARFP) or core+1 protein is one the newest ones that can promote persistent infection (10)(11)(12). This protein is produced by a frame shift at codon 11 by a minority of ribosomes that initiate translation at the HCV AUG initiator codon of HCV genome (13,14).…”

Comparison of biomarkers between genotypes 1a and 3a in hepatitis C virus patients with control group

“…It has been shown that in chronic HCV patients, 82% were positive for anti-F antibodies, showing a significant difference from the healthy individuals 5 . This protein increases the frequency of CD4+CD25+ Treg cells, which may be associated with persistent and chronic infection through subversion of the host immune response 6 F proteins could also enhance liver cell proliferation 7 , which is subsequently associated with the disease progression towards cirrhosis 8 . The protease function of HCV NS3 protein is also a crucial factor for the induction of liver fibrosis via interaction with cellular miRNAs and down-regulation of miRNA gene expressions 9,10 .…”