title: Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter.
abstract: BACKGROUND
  HIV-1 transcription initiation depends on cellular transcription factors that bind to promoter sequences in the Long Terminal Repeat (LTR). Each HIV-1 subtype has a specific LTR promoter configuration and even minor sequence changes in the transcription factor binding sites (TFBS) or their arrangement can impact transcriptional activity. Most latency studies have focused on HIV-1 subtype B strains, and the degree to which LTR promoter variation contributes to differences in proviral latency is therefore largely unknown. Latency differences may influence establishment and size of viral reservoirs as well as the possibility to clear the virus by therapeutic intervention.
  
  
  RESULTS
  We investigated the proviral transcriptional latency properties of different HIV-1 subtypes as their LTRs have unique assemblies of transcription factor binding sites. We constructed recombinant viral genomes with the subtype-specific promoters inserted in the common backbone of the subtype B LAI isolate. The recombinant viruses are isogenic, except for the core promoter region that encodes all major TFBS, including NFκB and Sp1 sites. We developed and optimized an assay to investigate HIV-1 proviral latency in T cell lines. Our data show that the majority of HIV-1 infected T cells only start viral gene expression after TNFα activation.
  
  
  CONCLUSIONS
  There were no gross differences among the subtypes, both in the initial latency level and the activation response, except for subtype AE that combines an increased level of basal transcription with a reduced TNFα response. This subtype AE property is related to the presence of a GABP instead of NFκB binding site in the LTR.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Renée M
authors.initials: RM
authors.lastname: van der Sluis
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.forename: Marja L
authors.initials: ML
authors.lastname: van Gerven
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Rienk E
authors.initials: RE
authors.lastname: Jeeninga
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013045:Species Specificity; D017735:Virus Latency; D014779:Virus Replication