Antiretroviral drug therapy alters the profile of human immunodeficiency virus type 1-specific T-cell responses and shifts the immunodominant cytotoxic T-lymphocyte response from Gag to Pol.
Antiretroviral drug therapy and cytotoxic T lymphocytes (CTL) both exert selective pressures on human immunodeficiency virus type 1, which influence viral evolution. Compared to chronically infected, antiretroviral-untreated patients, most chronically infected, treated patients with detectable viremia lack a cellular immune response against the Gag 77-85(SL9) epitope but show a new immunodominant response against an epitope in protease PR 76-84. Hence, mutations induced by antiretroviral therapy likely alter the profile of epitopes presented to T cells and thus the direction of the response. The consequences of dual pressures from treatment and CTL need to be considered in monitoring of drug therapy.
Karlsson
A C
AC
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA. annika.karlsson@smi.ki.se
Chapman
J M
JM
Heiken
B D
BD
Hoh
R
R
Kallas
E G
EG
Martin
J N
JN
Hecht
F M
FM
Deeks
S G
SG
Nixon
D F
DF
D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D015683:Gene Products, gag / Q000276:immunology*; D015684:Gene Products, pol / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D016056:Immunodominant Epitopes; D008969:Molecular Sequence Data; D009154:Mutation; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D044966:Anti-Retroviral Agents; D015683:Gene Products, gag; D015684:Gene Products, pol; D016056:Immunodominant Epitopes