Tat-specific cytotoxic T lymphocytes select for SIV escape variants duringresolution of primary viraemia

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as str ong cellular immune responses develop(1,2). Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection(3-11), the data have been controvers ial(12,13). Here we show that Tat-specific CD8-positive T-lymphocyte respon ses select for new viral escape variants during the acute phase of infectio n. We sequenced the entire virus immediately after the acute phase, and fou nd that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in contro lling wild-type virus replication, and suggests that responses against vira l proteins that are expressed early during the viral life cycle might be at tractive targets for HIV vaccine development.