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. 1997 Nov;71(11):8657–8665. doi: 10.1128/jvi.71.11.8657-8665.1997

Divergent transcriptional regulation among expanding human immunodeficiency virus type 1 subtypes.

M A Montano 1, V A Novitsky 1, J T Blackard 1, N L Cho 1, D A Katzenstein 1, M Essex 1
PMCID: PMC192329  PMID: 9343223

Abstract

The current AIDS pandemic represents the uneven spread of multiple genetically related subtypes (A to J) of human immunodeficiency virus type 1 (HIV-1). Notably, HIV-1 E in southeast Asia and HIV-1 C in sub-Saharan Africa are expanding faster and are likely of greater global significance than the HIV-1 B subtype prevalent in the United States and Europe. While many studies have focused on genetic variation among structural genes, we chose to conduct a comparative analysis of the long terminal repeats of HIV-1 E and HIV-1 C isolates and report subtype-specific differences in enhancer copy numbers and sequences, as well as divergent activation in response to the cellular transcriptional activators Rel-p65 and NFATc and viral Tat. This study is the first to identify functional distinctions in promoter architecture between HIV-1 subtypes and raises the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. Divergent transcriptional regulation may explain some of the epidemiologically observed differences in transmission and pathogenesis and underscores the need for further comparative analysis of HIV-1 regulation.

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Selected References

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