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Hepatitis C virus core protein reduces CD 8 + T‐cell proliferation, perforin production and degranulation but increases STAT 5 activation
Author(s) -
Khan Sarwat Tahsin,
Karges Winston,
Cooper Curtis L.,
Crawley Angela M.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12882
Subject(s) - perforin , biology , degranulation , hepatitis c virus , cytotoxic t cell , t cell , immunology , virology , cd8 , microbiology and biotechnology , virus , antigen , immune system , in vitro , biochemistry , receptor
Summary Clearance of hepatitis C virus ( HCV ) is dependent on an effective virus‐specific CD 8 + T‐cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non‐ HCV ‐specific CD 8 + T‐cells in HCV infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.g. cancer, viral co‐infections) in HCV ‐infected individuals. Evidence suggests that the HCV core protein (found in blood as free protein) may contribute to this impairment. To determine if HCV core contributes to the impairment of effector functions and survival potential of CD 8 + T‐cells, isolated human CD 8 + T‐cells from healthy donors were pre‐incubated with recombinant HCV core protein for 72 hr and then stimulated in vitro to evaluate proliferation, survival potential and effector functions. Pre‐incubation of stimulated CD 8 + T‐cells with HCV core significantly reduced their proliferation. Perforin production and degranulation were also decreased, but interferon‐ γ production was unchanged. Additionally, when CD 8 + T‐cells were treated with serum from HCV + individuals, they produced less perforin than cells treated with healthy serum. Up‐regulation of anti‐apoptotic Bcl‐2 was slightly lower in cells treated with HCV core, but signal transducer and activator of transcription 5 ( STAT 5) activation was increased, suggesting dysregulation downstream of STAT activation. Our study reveals that HCV core reduces the activity and target lysis‐associated functions of CD 8 + T‐cells. This may contribute to the generalized impairment of CD 8 + T‐cells observed in HCV infection. These findings provide insight for the design of novel counteractive immune‐mediated strategies including the design of effective therapeutic vaccines for use in HCV + individuals.