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Evolution of viral quasispecies in four dominant HlA‐A2 restricted T cell epitopes is not a major reason for viral persistence in interferon‐treated patients with chronic hepatitis C
Author(s) -
Pingel Sabine,
Weyer Sandra,
Galle Peter R.,
Löhr Hanns F.
Publication year - 2002
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.2168
Subject(s) - viral quasispecies , epitope , virology , biology , human leukocyte antigen , hepatitis c virus , interferon , virus , immunology , antibody , antigen
In most patients, chronic hepatitis C virus (HCV) infection persists despite antiviral treatment with interferon‐alpha (IFN‐α) and ribavirin. The aim of the study was to determine whether HCV could evade cellular immune responses through mutations within T cell epitopes. Viral sequences flanking four major CTL epitopes within the HCV core and envelope regions were analyzed by PCR amplification, cloning and sequencing in seven HLA‐A2 positive HCV patients before, during and after antiviral therapy. In addition, cytotoxic T lymphocyte precursor (CTLp) frequencies specific to these epitopes were quantitated by ELISPOT. A total of 13 coding mutations were observed among 650 cloned and sequenced PCR products under or post IFN treatment but no clear selection of viral variants. In detail, the diversity of quasispecies in the two core epitopes remained fairly stable over time despite variable CTLp induction in some individuals. The overall mutation rate in the two envelope epitopes was higher but there was no correlation with specific CTLp frequencies. In conclusion, although evolution of the viral quasispecies during and after antiviral therapy was demonstrated, immune evasion by epitope specific mutations seemed to be not common in interferon nonresponders because the viral complexity did not increase. J. Med. Virol. 66:472–480, 2002. © 2002 Wiley‐Liss, Inc.