title: Differential regulation of human immunodeficiency virus type 2 and simian immunodeficiency virus promoter activity.
abstract: Promoter activity of the HIV-1 long terminal repeat (LTR) is largely dependent on intact NF-kB and SpI binding sites in the U3 region. In contrast, upstream LTR sequences allow efficient simian immunodeficiency virus (SIVmac) transcription in the absence of the core enhancer promoter region. In the present study, we investigated whether the regulation of HIV-2 Rod LTR activity is more reminiscent of HIV-1 having the same host or of SIVmac239 belonging to the same phylogenetic group. Viral promoter activity was studied in the context of the integrated provirus using both single cycle assays with pseudotyped luciferase reporter viruses and replication-competent HIV-2 LTR mutants. Our results demonstrate that intact SpI binding sites are important for both HIV-2 and SIVmac LTR activity in T cells and monocyte-derived macrophages. In contrast, deletion of the NF-kB binding site or of upstream regulatory sequences impaired HIV-2 Rod LTR activity but had little effect on SIVmac239 promoter function. Thus, similar to HIV-1, regulation of HIV-2 LTR promoter activity shows a low degree of functional redundancy possibly suggesting a specific adaptation to the human host.
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hiebenthal-Millow
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D017353:Gene Deletion; D016322:HIV Enhancer / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000502:physiology; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014158:Transcription, Genetic; D014779:Virus Replication