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Background. HBcAg-specific regulatory T (Treg) cells play an important role in the pathogenesis of chronic hepatitis B. Soluble heat shock proteins, especially soluble heat shock protein 60 (sHSP60), could affect the function of Treg cells via Toll-like receptor. Methods. We analyzed the relationship between soluble heat shock protein production and hepatitis B virus (HBV) replication with both clinical samples from HBeAg-positive patients with chronic hepatitis B (n = 24) and HBeAb-positive patients with chronic hepatitis B (n = 24) and in vitro HBV-replicating hepatocytes. Thereafter, we examined the biological effects of sHSP60 with isolated Treg cells. Results. The serum levels of sHSP60 in patients with chronic hepatitis B were statistically significantly higher than those in patients with chronic hepatitis C (P < .01), and the levels of sHSP60 were correlated with the HBV DNA levels (R = 0.532; P < .001) but not with the alanine aminotransferase levels. Moreover, the levels of sHSP60 in HBV-replicating HepG2 cells were statistically significantly higher than those in control HepG2 cells. Preincubation of CD4+ CD25+ cells with recombinant HSP60 (1 ng/mL) statistically significantly increased the frequency of HBcAg-specific interleukin 10-secreting Treg cells. The frequency of IL7R-CD4+ CD25+ cells, the expression of Toll-like receptor 2, and the suppressive function of Treg cells had declined during entecavir treatment. Conclusion. The function of HBcAg-specific Treg cells was enhanced by sHSP60 produced from HBV-infected hepatocytes. Entecavir treatment suppressed the frequency and function of Treg cells; this might contribute to the persistence of HBV infection. [ABSTRACT FROM AUTHOR]

Background. A lymphotropic hepatitis C virus strain (HCV, SB strain, hereafter "SB-HCV") has been shown to infect established T cell lines (Molt-4 and Jurkat) and primary human naive CD4+ T cells. During T cell development and activation, transient expression of CD44 splicing variant 6 (CD44v6) plays a significant role. Methods. SB-HCV was used to infect Molt-4 cells, and their cellular proliferation and CD44 expression was examined. Results. SB-HCV-infected Molt-4 cells expressed a significantly lower level of the CD44v6 isoform. The infected cells could be divided into 2 carboxyfluorescein succinimidyl ester (CFSE) groups, CFSE-high (indicating low proliferation activity; 34.2% of the cells) and CFSE-low (indicating high proliferation activity; 62.5% of the cells), whereas uninfected cells consisted of only a CFSE-low population. Of the CFSE-high cells, 82.4% were positive for the HCV protein NS5A , whereas only 1.2% of the CFSE-low cells were positive for this protein. Among the HCV proteins, NS5A alone caused the down-regulation of CD44v6 expression. After cells were stimulated with phorbol myristate acetate, the amount of phosphorylated mitogen-activated protein (MAP) kinase was significantly reduced in CFSE-high, SB-HCV-infected Molt-4 cells. After Fas ligand stimulation, SB-HCV-infected Molt-4 cells had increased cleavage of caspase 8 and 3 and enhanced apoptosis, compared with the rates of cleavage and apoptosis in control groups, indicating that SB-HCV infection increased Fas-mediated apoptosis. Conclusion. HCV replication in T cells suppresses cellular proliferation and enhances susceptibility to Fas signaling by inhibiting CD44v6 signaling and expression. [ABSTRACT FROM AUTHOR]