Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1

Transcription of the HIV-1 provirus genome is regulated by a complex interp lay between viral regulatory proteins and cellular transcription factors th at interact with the viral long terminal repeat (LTR) region of HIV-1, Howe ver, several cellular transcription factors have been identified that can i nteract 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 regi ons were sequenced and further analyzed for promoter/enhancer activity in t ransient transfection of HeLa cells, in the context of a reporter gene and in the context of the complete virus genome. We found several subtype-speci fic LTR sequences of the various HIV-1 strains, such as an insertion that c reated a potential third NF-kappa B site in the LTR of the subtype C strain s. The USF-binding site in the NRE also contained subtype-specific sequence s. Interestingly, the promoter/enhancer activities of the subtype C LTRs we re higher than the activities of the other subtypes analyzed here (subtypes A, B, D, E, and G), suggesting that the potential third NF-kappa B site ma y 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.