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Báo cáo y học: "Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter. | van der Sluis et al. Retrovirology 2011 8 73 http www.retrovirology.eom content 8 1 73 RETR0VIR0L0GY RESEARCH Open Access Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter Renée M van der Sluis Georgios Pollakis Marja L van Gerven Ben Berkhout and Rienk E Jeeninga 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 NFkB 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 TNFa 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 TNFa response. This subtype AE property is related to the presence of a GABP instead of NFkB binding site in the LTR. .