Transient Tat activation of the HIVLAV/Lai-1 LTR by primary HIV-1 phenotypic variants in HeLaT4LTRbeta-gal cells.

Abstract

The rapid/high and slow/low phenotypic variants of primary HIV-1 isolates can be distinguished by their differential co-receptor utilization and their ability to productively infect established cell lines. To reveal possible differences in Tat-mediated transactivation, the potential for primary isolate Tat proteins to transactivate the LTR from the laboratory strain HIVLAV/Lai-1 was examined. Using either cell-mediated or PEG-induced fusion of cells infected with primary HIV-1 isolates and HeLaT4LTRbeta-gal cells, it was clear that the Tat protein encoded by all patient isolates efficiently activated transcription from the HIVLAV/Lai-1 LTR. However, infection of HeLaT4LTRbeta-gal cells by primary HIV-1 isolates was transient, suggesting the development of a postpenetration host control of HIV-1 replication at the level of tat activation, a feature not observed for the laboratory-adapted strain HIVIIIB. Although plasmid vectors based on the HIVLAV/Lai-1 LTR remain useful for the development of susceptible established cell lines for titrating primary HIV-1 isolates, the efficacy of such a system would depend upon the stability/duration of Tat activation.