Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells

Numerous factors are known to bind human immunodeficiency virus (HIV) long terminal repeat (LTR) and activate viral transcription, but little is known as to how they function in naturally activated T cells and to what extent their binding is relevant to HIV replication in rico. To characterize the H IV LTR-binding factors responsible for antigen-dependent activation of HIV, we examined replication of LTR mutant viruses in CD4(+) T cells activated by different stimuli, NF-kappa B or Sp1 mutant virus replicated well in CD4 (+) T cells activated by phorbol ester and calcium ionophore. When they wer e activated by antigen-pulsed dendritic cells, the replication of the Sp1-d eleted virus was severely impaired in CD45RA(+), but not in CD45RO(+) T cel l subsets that dominantly produce interleukin-2 (IL-2). Stimulation via CD3 /CD28 induced a high level of IL-2 production in both T cell subsets, but S p1-deleted virus poorly replicated in CD45RA(+) subset. The level of NF-kap pa B and Sp1-binding factors did not differ between these subsets. Our resu lts suggest that additional cofactors distinct from IL-2-inducing signaling molecules are important for LTR activation during antigen-dependent T cell activation.