Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients

It is unknown whether hepatitis C virus (HCV)‐specific cellular immune responses can develop in seronegative sexual partners of chronically HCV‐infected patients and whether they have occult infection. Thirty‐one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti‐HCV seropositive patients, without viremia, were used as controls. Virus‐specific CD4+ and CD8+ T‐cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN‐γ) or interleukin 4 (IL‐4) production and CD69 expression. Sexual partners had a higher production of IFN‐γ and IL‐4 by CD4+ cells against NS3‐p124 (P = 0.003), NS5b‐p257 (P = 0.005) and NS5b‐p294 (P = 0.012), and CD8+ cells against NS3‐p124 (P = 0.002), NS4b‐p177 (P = 0.001) and NS3‐p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN‐γ production by CD4+ T cells against NS5b‐p257 (P = 0.042) and NS5b‐p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV‐RNA positive and replicative (negative) strands was performed by strand‐specific real‐time PCR. In four sexual partners, the presence of positive and negative HCV‐ RNA strands in PBMC was confirmed. Hence, we found an HCV‐specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV‐infected patients.