Ma. Montano et al., DIVERGENT TRANSCRIPTIONAL REGULATION AMONG EXPANDING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPES, Journal of virology, 71(11), 1997, pp. 8657-8665
The current AIDS pandemic represents the uneven spread of multiple gen
etically related subtypes (A to J) of human immunodeficiency virus typ
e 1 (HIV-1). Notably, HIV-1 E in southeast Asia and HIV-1 C in sub-Sah
aran Africa are expanding faster and are likely of greater global sign
ificance than the HIV-1 B subtype prevalent in the United States and E
urope. While many studies have focused on genetic variation among stru
ctural genes, we chose to conduct a comparative analysis of the long t
erminal repeats of HIV-1 E and HIV-1 C isolates and report subtype-spe
cific differences in enhancer copy numbers and sequences, as well as d
ivergent activation in response to the cellular transcriptional activa
tors Rel-p65 and NFATc and viral Tat. This study is the first to ident
ify functional distinctions in promoter architecture between HIV-1 sub
types and raises the possibility that regulatory divergence among the
subtypes of HIV-1 has occurred. Divergent transcriptional regulation m
ay explain some of the epidemiologically observed differences in trans
mission and pathogenesis and underscores the need for further comparat
ive analysis of HIV-1 regulation.