Roles of target cells and virus-specific cellular immunity in primary simian immunodeficiency virus infection

There is an ongoing debate on whether acute human immunodeficiency virus infection is controlled by target cell limitation or by virus-specific cellular immunity. To resolve this question, we developed a novel mathematical modeling scheme which allows us to incorporate measurements of virus load, target cells, and virus-specific immunity and applied it to a comprehensive data set generated in an experiment involving rhesus macaques infected with simian immunodeficiency virus. Half of the macaques studied were treated during the primary infection period with reagents which block T-cell costimulation and as a result displayed severely impaired virus-specific immune responses. Our results show that early viral replication in normal infection is controlled to a large extent by virus-specific CD8(+) T cells and not by target cell limitation.