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.
Zhang
J
J
New Jersey Center for Advanced Biotechnology and Medicine (CABM), University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, USA.
Novembre
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F
Rabson
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000235:genetics*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D010835:Phytohemagglutinins; D011494:Protein Kinases; C065999:Sp1 kinase