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.

Pertussis Toxin B-Oligomer Suppresses IL-6 Induced HIV-1 and Chemokine Expression in Chronically Infected U1 Cells via Inhibition of Activator Protein 1

“…Alternatively, PTX-B could downregulate AP-1 mediated activation of the intragenic gag enhancer (48,60), previously suggested to be induced by stimuli, such as IL-6, in combination with TNF-␣ or glucocorticoids (38,49). In this regard, our findings on the levels of luciferase expression driven by LTRs after IL-6 stimulation add to previous reports on biological differences among the different HIV clades, which are determined in part by differences in the composition of the LTR promoter (52,(77)(78)(79)(80). Thus, differences in the composition of transcription factor binding sites may provide each clade with a promoter responding in a unique matter to cellular activation pathways.…”

Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade Cenv

“…In addition, a correlation between HIV-1 LTR subtype configuration of the NF-B promoter region and responsiveness to TNF-␣ was reported earlier (37). The data derived from the in vitro pLuc expression controlled by a truncated LTR with zero to two NF-B binding elements support the previously held notion (26,37,40) that the number of NF-B binding sites in the LTR directly correlates with the level of gene expression driven by the LTRs. As expected, the additional NF-B binding element in the SHIV-1157ipd3N4 LTRs rendered our virus more responsive to the effects of TNF-␣ than SHIV-1157ipd3.…”

HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo

“…In clade E promoters, only 1 NF-κB binding site is present along with an upstream active GA-binding protein (GABP) site (11) (Figure 1A). In vitro and ex vivo data have shown that the core promoter/enhancer is sufficient to promote viral replication (12) and that host cell type and the activation state of the cell affect viral replication, depending on viral promoter polymorphism (6).…”