INHIBITION OF HIV-1 REPLICATION AND REACTIVATION FROM LATENCY BY TAT TRANSDOMINANT NEGATIVE MUTANTS IN THE CYSTEINE-RICH REGION

Tat mutants (tat22, tat37 and tat22/37) were constructed in the transa ctivation domain, where cysteines at positions 22 or/and 37 were subst ituted with glycine and serine, respectively. These mutants were expre ssed either in a BK virus episomal vector or in the retroviral vector LXSN. Constitutive production of tat22 by Jurkat T cells in the contex t of both vectors blocked HIV-1 replication during lytic infection. Co nversely, the tat37 mutant did not show any inhibitory activity and ta t22/37 displayed a mild effect on HIV-1 infection only when expressed by the recombinant retrovirus. However, constitutive production of tat 22/37 by the BK virus vector in Jurkat T cells chronically infected by HIV-1 was effective in blocking reactivation of viral replication ind uced by tumor necrosis factor-alpha or human herpesvirus-6. These resu lts suggest that mutants in the transactivation domain of tat may be c onsidered in designing alternative strategies to control HIV-1 replica tion and reactivation from latency during different phases of infectio n.