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.
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141, USA. annika.karlsson@smi.ki.se
A C
AC
Karlsson
J M
JM
Chapman
B D
BD
Heiken
R
R
Hoh
E G
EG
Kallas
J N
JN
Martin
F M
FM
Hecht
S G
SG
Deeks
D F
DF
Nixon
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