Single amino acid change in Tat determines the different rates of replication of two sequential HIV-1 isolates

Human immunodeficiency virus type 1 (HIV-1) isolates display differences in their patterns of replication in vitro. Previous studies with recombinant viruses generated between two sequential HIV-1 isolates that differ in replication rates have shown that the determinant for this biological property maps to a region of the viral genome that encompasses the tat gene. In the present study, we examined if there is a functional difference in the Tat protein of the two isolates. We observed that the level of transactivation induced by Tat of the fast replicating, highly cytopathic virus (HIV-1SF13mc) was three- to eightfold higher than the level seen by the Tat of the slow replicating virus (HIV-1SF2mc). Furthermore, a single amino acid mutation in the HIV-1SF13mc. Tat leads to reduced transactivation activity of the mutant protein and a delayed replication rate of the mutant virus. Thus, selection of a Tat variant with higher transactivation potential could be responsible for the increased virus production that is often associated with a pathogenic HIV strain.