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Journal of Virology, May 2000, p. 4666-4671, Vol. 74, No. 10
Howard Hughes Medical
Institute1 and Department of
Genetics,2 Duke University Medical Center,
Durham, North Carolina
Received 2 December 1999/Accepted 16 February 2000
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 factor 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 gene 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. Species, such as
rodents, that encode cyclin T1 variants that are unable to support TAR
binding by the Tat-cyclin T1 heterodimer are also unable to support
HIV-1 Tat function. In contrast, we here demonstrate that the bovine
immunodeficiency virus (BIV) Tat protein is fully able to bind to BIV
TAR both in vivo and in vitro in the absence of any cellular cofactor.
Nevertheless, BIV Tat can specifically recruit cyclin T1 to the BIV TAR
element, and this 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 TAR binding, BIV Tat is able to function effectively in cells from several species that do not support HIV-1 Tat
function. Thus, BIV Tat, while apparently dependent on the same
cellular cofactor as the Tat proteins encoded by other lentiviruses, is
nevertheless unique in terms of the mechanism used to recruit the BIV
Tat-cyclin T1 complex to the viral LTR promoter.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Functional Differences between Human and Bovine Immunodeficiency
Virus Tat Transcription Factors
and
*
Corresponding author. Mailing address: Howard Hughes
Medical Institute, Duke University Medical Center, Box 3025, Durham, NC
27710. Phone: (919) 684-3369. Fax: (919) 681-8979. E-mail: culle002{at}mc.duke.edu.
Present address: Aaron Diamond AIDS Research Center, Rockefeller
University, New York, NY 10021.
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