Hp. Bogerd et al., Functional differences between human and bovine immunodeficiency virus tartranscription factors, J VIROLOGY, 74(10), 2000, pp. 4666-4671
Transcriptional transactivation of the human immunodeficiency virus type 1
(HIV-1) long terminal repeat (LTR) promoter element by the essential viral
Tat protein requires recruitment of positive transcription elongation facto
r b (P-TEFb) to the viral TAR RNA target. The recruitment of P-TEFb, which
has been proposed to be necessary and sufficient for activation of viral ge
ne expression, is mediated by the highly cooperative interaction of Tat and
cyclin T1, an essential component of P-TEFb with the HIV-1 TAR element. Sp
ecies, such as rodents, that encode cyclin T1 variants that are unable to s
upport TAR binding by the Tat-cyclin T1 heterodimer are also unable to supp
ort HIV-1 Tat function. In contrast, we here demonstrate that the bovine im
munodeficiency virus (BIV) Tat protein is fully able to bind to BIV TAR bot
h in vivo and in vitro in the absence of any cellular cofactor. Nevertheles
s, BIV Tat can specifically recruit cyclin T1 to the BIV TAR element, and t
his recruitment is as essential for BIV Tat function as it is for HIV-1 Tat
activity. However, because the cyclin T1 protein does not contribute to TA
R binding, BIV Tat is able to function effectively in cells from several sp
ecies that do not. support HIV-1 Tat function. Thus, BIV Tat, while apparen
tly dependent on the same cellular cofactor as the Tat proteins encoded by
other lentiviruses, is nevertheless unique in terms of the mechanism used t
o recruit the BIV Tat-cyclin T1 complex to the viral LTR promoter.