HOST CONTROL OF HIV-1 PARASITISM IN T-CELLS BY THE NUCLEAR FACTOR OF ACTIVATED T-CELLS

Post HIV-1 entry, productive HIV-1 infection of primary T cells requir es overcoming several cellular blocks to provirus establishment and re plication. Activation of unknown host intracellular events overcomes s uch inhibitory steps and is concomitant with HIV-1 replication. We sho w that the transcription factor NFATc was sufficient as a cellular fac tor to induce a highly permissive state for HIV-1 replication in prima ry CD4(+) T cells. NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication. Pharmacologic blockade of endo genous NFAT activity by FK506 or CsA inhibited synthesis of reverse tr anscription and also potently blocked HIV-1 replication. T cells there fore can become competent for HIV-1 replication by control of regulate d host factors such as the NFATc transcription factor. The host mechan isms regulated by such permissivity factors are potential targets for anti-HIV-1 therapy.