R. Vanitharani et al., HIV-1 Vpr transactivates LTR-directed expression through sequences presentwithin-278 to-176 and increases virus replication in vitro, VIROLOGY, 289(2), 2001, pp. 334-342
Human immunodeficiency virus type 1 (HIV-1) Vpr, a 14-kDa virion-associated
protein, plays an important role in the viral life cycle. Using a panel of
truncated HIV-1 LTR-CAT constructs and Vpr expression plasmid, we have ide
ntified sequences from nucleotide -278 to -176 in LTR as Vpr-mediated trans
activation domain. This region includes the glucocorticoid response element
(GRE) in HIV-1 LTR. Transactivation by Vpr was noted with the HIV-1 LTR re
porter constructs containing CAT or luciferase. A similar effect was also o
bserved with a construct in which the GRE motif was linked to CAT. Studies
involving Vpr mutants identified that helical domains I and III, and amino
acid residues at G75 and C76, are responsible for GRE-mediated LTR transact
ivation. The transactivation function of Vpr is independent of its cell cyc
le arrest activity, Further, viral replication studies indicated that Vpr-m
ediated increase in viral replication is directly correlated with the abili
ty of Vpr to transactivate HIV-1 LTR. The results presented here demonstrat
e that Vpr activates HIV-1 LTR through the host GR pathway and suggest that
an intact GRE in the LTR is critical for Vpr activity. (C) 2001 Academic P
ress.