SIMIAN IMMUNODEFICIENCY VIRUSES CONTAINING MUTATIONS IN THE LONG TERMINAL REPEAT NF-KAPPA-B OR SPL BINDING-SITES REPLICATE EFFICIENTLY IN T-CELLS AND PHA-STIMULATED PBMCS

The long terminal repeats (LTRs) of primate lentiviruses contain conse rved binding sites for the NF-kappa B and Sp1 cellular transcription f actors. In order to study the role that these sites play in simian imm unodeficiency virus (SIV) replication, we have introduced mutations th at disrupt either the NF-kappa B or Sp1 binding sites in the LTR of an infectious molecular clone of SIVmac239. An additional mutation also disrupted the SF3 transcription factor binding site that overlaps the NF-kappa B site. Viruses containing point mutations or deletions of th e NF-kappa B, SF3, or Sp1 binding sites retained the ability to replic ate efficiently in the CEMx174 and MT4 cell lines, as well as in PHA-s timulated primary rhesus macaque peripheral blood mononuclear cells (P BMCs). Efficient replication of STVs mutated in either NF-kappa B or S p1 binding sites suggests that the SIV LTR promoter contains multiple functionally redundant elements capable of supporting sufficient trans cription to allow productive viral replication. (C) 1997 Elsevier Scie nce B.V.