Functional differences between human and bovine immunodeficiency virus Tat transcription factors.
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.
Bogerd
H P
HP
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Wiegand
H L
HL
Bieniasz
P D
PD
Cullen
B R
BR
D000818:Animals; D002417:Cattle; D002460:Cell Line; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016087:Immunodeficiency Virus, Bovine / Q000378:metabolism*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; D012367:RNA, Viral; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus