Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

Abstract

The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays.

Virus-Specific Cellular Response in Hepatitis C Virus Infection

“…It is not clear whether the cellular response in exposed individuals is more frequent after stimulation with HCV core antigen (Della Bella et al 2005;Riviere et al 2012), or with non-structural antigens, in particular NS5 (Hashem et al 2011). Surprisingly, the virus-specific cellular response in non-infected individuals exposed to HCV is more frequent, stronger and directed against greater Proliferation assai (Cramp et al 1999) 16 (n = 14) CD4 ?…”

“…Different studies of HCV-specific cellular response among persistently infected individuals can be detectable in a surprising broad range from 12.5 to 69.0 % of Day et al 2002;Riviere et al 2012;Rosen et al 2002;Zhang et al 2009). Majority of studies report that the reactivity of CD4 ?…”

“…This type of response may be present in PWIDs, medical staff, family members, sexual partners of infected persons with frequency ranging 0-36 % (Al-Sherbiny et al 2005;Hashem et al 2011;Riviere et al 2012;Scognamiglio et al 1999). In particular, it is prevalent in more than 60 % of healthy children born to mothers infected with the virus (Della Bella et al 2005;Hashem et al 2011).…”

“…In the majority of cases (60-85 %) hepatitis C virus (HCV) infection is primarily chronic since the virus efficiently evades adaptive immunity (Maheshwari et al 2008;Riviere et al 2012;Sarobe et al 2002;Strickland et al 2008) and the late consequences of infection are liver cirrhosis and hepatocellular carcinoma (Neumann-Haefelin et al 2005;Tatsumi et al 2011). The main factor determining elimination of HCV is effective immune response (Zhang et al 2009).…”

Frequent Transient Hepatitis C viremia without Seroconversion among Healthcare Workers in Cairo, Egypt

“…Prior studies into the existence of transient HCV viremia have documented cases among individuals with high-risk exposures, such as HCWs [4] or prison inmates [5], [6]. Additionally, some studies have shown that subjects with high-risk exposure to HCV could induce cell-mediated immunity in the absence of detectable viremia or seroconversion, among HCWs [7], [8], people living with HCV-infected subjects [9], [10] and sexual partners of infected individuals [11], [12].…”