Second exon of Tat of HIV-2 is required for optimal trans-activation of HIV-1 and HIV-2 LTRs.

To determine conditions for optimal trans-activation by Tat of HIV-2, genomic DNAs and cDNAs encoding Tat of HIV-2 were tested on their homologous (HIV-2) and heterologous (HIV-1) long terminal repeats (LTRs). It has been previously reported that Tat of HIV-2 could efficiently trans-activate only its own LTR but not that of HIV-1. The inefficient trans-activation of HIV-1 is due, in part, to an acidic residue in the basic, RNA-binding domain of Tat of HIV-2. Here we demonstrate that inefficient trans-activation of HIV-1 LTR is observed only with plasmids that express exon 1 and genomic forms of tat of HIV-2. Expression of both exons of Tat of HIV-2 from cDNA results in trans-activation of HIV-1 that is equivalent to the effect of Tat of HIV-1. In addition, the cDNA form of tat of HIV-2 trans-activates the HIV-2 LTR more efficiently than exon 1 and genomic forms of tat of HIV-2. We conclude that exon 2 of Tat of HIV-2 is important for optimal interactions with the trans-acting responsive regions (TARs) of HIV-1 and HIV-2 and that differential expression of short and full-length Tats of HIV-2 during the viral life cycle might affect viral latency, levels of viral replication, and cellular cytopathology.