Abstract
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV)
infections are characterized by early peaks of viraemia that decline as strong
cellular immune responses develop. Although it has been
shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert
selective pressure during HIV and SIV infection,
the data have been controversial. Here we show that Tat-specific
CD8-positive T-lymphocyte responses select for new viral escape variants during
the acute phase of infection. We sequenced the entire virus immediately after
the acute phase, and found that amino-acid replacements accumulated primarily
in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly
involved in controlling wild-type virus replication, and suggests that responses
against viral proteins that are expressed early during the viral life cycle
might be attractive targets for HIV vaccine development.
