Ma. Montano et al., DYSREGULATION THROUGH THE NF-KAPPA-B ENHANCER AND TATA BOX OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPE-E PROMOTER, Journal of virology, 72(10), 1998, pp. 8446-8452
The global diversity of human immunodeficiency virus type 1 (HIV-1) ge
notypes, termed subtypes A to J, is considerable and growing, However,
relatively few studies have provided evidence for an associated pheno
typic divergence, Recently, we demonstrated subtype-specific functiona
l differences within the long terminal repeat (LTR) region of expandin
g subtypes (M. A. Montano, V. A. Novitsky, J. T, Blackard, N. L. Cho,
D, A. Katzenstein, and M, Essex, J, Virol, 71:8657-8665, 1997), Notabl
y, all HIV-1E isolates were observed to contain a defective upstream N
F-kappa B site and a unique TATA-TAR region. In this study, we demonst
rate that tumor necrosis factor alpha (TNF-alpha) stimulation of the H
IV-1E LTR was also impaired, consistent with a defective upstream NF-k
appa B site. Furthermore, repair of the upstream NF-kappa B site withi
n HIV-1E partially restored TNF-alpha responsiveness. We also show, in
gel shift assays, that oligonucleotides spanning the HIV-1E TATA box
displayed a reduced efficiency in the assembly of the TBP-TFIIB-TATA c
omplex, relative to an HIV-1B TATA oligonucleotide. In transfection as
says, the HIV-1E TATA, when changed to the canonical HIV-1B TATA seque
nce (ATAAAA-->ATAATA) unexpectedly reduces both heterologous HIV-1B Ta
t and cognate HIV-1E Tat activation of an HIV-1E LTR-driven reporter g
ene. However, Tat activation, irrespective of subtype, could be rescue
d by introducing a cognate HIV-1B TAR. Collectively, these observation
s suggest that the expanding HIV-1E genotype has likely evolved an alt
ernative promoter configuration with altered NF-kappa B and TATA regul
atory signals in contradistinction with HIV-1B.