Simian immunodeficiency viruses containing mutations in the long terminal repeat NF-kappa B or Sp1 binding sites replicate efficiently in T cells and PHA-stimulated PBMCs.

The long terminal repeats (LTRs) of primate lentiviruses contain conserved binding sites for the NF-kappa B and Sp1 cellular transcription factors. In order to study the role that these sites play in simian immunodeficiency virus (SIV) replication, we have introduced mutations that 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 the NF-kappa B, SF3, or Sp1 binding sites retained the ability to replicate efficiently in the CEMx174 and MT4 cell lines, as well as in PHA-stimulated primary rhesus macaque peripheral blood mononuclear cells (PBMCs). Efficient replication of SIVs mutated in either NF-kappa B or Sp1 binding sites suggests that the SIV LTR promoter contains multiple functionally redundant elements capable of supporting sufficient transcription to allow productive viral replication.