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Journal of Virology, January 2000, p. 892-898, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interactions between Equine Cyclin T1, Tat, and TAR Are Disrupted by a Leucine-to-Valine Substitution Found in Human Cyclin T1

Ran Taube, Koh Fujinaga, Dan Irwin, Jörg Wimmer, Matthias Geyer, and B. Matija Peterlin*

Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143-0703

Received 16 July 1999/Accepted 4 October 1999

Transcriptional transactivators (Tat) from human immunodeficiency and equine infectious anemia viruses (HIV and EIAV) interact with their transactivation response elements (TAR) to increase the rates of viral transcription. Whereas the human cyclin T1 is required for the binding of Tat to TAR from HIV, it is unknown how Tat from EIAV interacts with its TAR. Furthermore, Tat from EIAV functions in equine and canine cells but not in human cells. In this study, we present sequences of cyclins T1 from horse and dog and demonstrate that their N-terminal 300 residues rescue the transactivation of Tat from EIAV in human cells. Although human and equine cyclins T1 bind to this Tat, only the equine cyclin T1 supports the binding of Tat to TAR from EIAV. Finally, a reciprocal exchange of the valine for the leucine at position 29 in human and equine cyclins T1, respectively, renders the human cyclin T1 active and the equine cyclin T1 inactive for Tat transactivation from EIAV. Thus, the collaboration between a specific cyclin T1 and Tat for their high-affinity interaction with TAR is a common theme of lentiviral transactivation.

* Corresponding author. Mailing address: UCSF Mt. Zion Box 0703, 3rd and Parnassus Ave., San Francisco, CA 94143-0703. Phone: (415) 502-1905. Fax: (415) 502-1901. E-mail: matija{at}itsa.ucsf.edu.

Journal of Virology, January 2000, p. 892-898, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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