title: Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1.
abstract: Transcription of the HIV-1 provirus genome is regulated by a complex interplay between viral regulatory proteins and cellular transcription factors that interact with the viral long terminal repeat (LTR) region of HIV-1. However, several cellular transcription factors have been identified that can interact with the HIV-1 LTR; the significance of all of these factors is not clearly understood. In this study we have characterized the LTR region of different subtypes of HIV-1 with regard to nucleotide sequence and promoter activity. The LTR regions of HIV-1 from peripheral blood mononuclear cells of 29 infected individuals originating from 10 different geographical regions were sequenced and further analyzed for promoter/enhancer activity in transient transfection of HeLa cells, in the context of a reporter gene and in the context of the complete virus genome. We found several subtype-specific LTR sequences of the various HIV-1 strains, such as an insertion that created a potential third NF-kappaB site in the LTR of the subtype C strains. The USF-binding site in the NRE also contained subtype-specific sequences. Interestingly, the promoter/enhancer activities of the subtype C LTRs were higher than the activities of the other subtypes analyzed here (subtypes A, B, D, E, and G), suggesting that the potential third NF-kappaB site may confer higher LTR activity or that the subtype C NRE may be less potent. Thus, our data suggest that genetic diversity of the LTR may result in HIV-1 subtypes with different replicative properties.
authors.affiliation: Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge/Stockholm, Sweden. muna@lab01.hs.sll.se
authors.forename: M H
authors.initials: MH
authors.lastname: Naghavi
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: A
authors.initials: A
authors.lastname: Vahlne
mesh_terms: D000328:Adult; D000349:Africa / Q000208:ethnology; D001483:Base Sequence; D001665:Binding Sites; D015500:Chloramphenicol O-Acetyltransferase; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D016322:HIV Enhancer / Q000235:genetics*; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D013548:Sweden / Q000208:ethnology; D014162:Transfection
chemical_list: D016655:HIV Core Protein p24; D016328:NF-kappa B; D015500:Chloramphenicol O-Acetyltransferase