Interactions between equine cyclin T1, Tat, and TAR are disrupted by a leucine-to-valine substitution found in human cyclin T1.
Abstract: 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.
Publication Date: 2000-01-07 PubMed ID: 10623752PubMed Central: PMC111610DOI: 10.1128/jvi.74.2.892-898.2000Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates how the transcriptional transactivator proteins (Tat) found in HIV and equine infectious anemia viruses (EIAV) interact with certain cyclins to improve the rate of viral transcription. The study reveals that a small mutation, changing leucine to valine, can swap the functionality of human and equine cyclin T1 in supporting Tat transactivation from EIAV.
Objective and Background of the Study
- The research aims at understanding the interaction dynamics between Transcriptional transactivators (Tat), found in both Equine Infectious Anemia Viruses (EIAV) and the Human Immunodeficiency Virus (HIV), with their respective Transactivation Response elements (TAR).
- Prior to this study, it was known that human cyclin T1 is essential for the binding of Tat to TAR in HIV. However, the exact method by which Tat from EIAV interacts with its TAR was not known.
- The study also aimed to inspect why Tat from EIAV performs in equine and canine cells, but fails to function in human cells.
Methodology and Findings
- The research presented sequences of cyclins T1 from horses and dogs, demonstrating that their N-terminal 300 residues can restore the transactivation capability of Tat from EIAV in human cells.
- While both human and equine cyclins T1 can bind to Tat from EIAV, only equine cyclin T1 supports the binding of Tat to TAR from EIAV.
- An intriguing finding of the study was that exchanging a valine for a leucine at position 29 in human and equine cyclins T1 would swap their functionalities. This means the human cyclin T1 would become active and the equine cyclin T1 would become inactive for Tat transactivation from EIAV.
Conclusions
- The research concluded that the interaction between a specific cyclin T1 and Tat aids their high-affinity interaction with TAR, a common phenomenon observed in lentiviral transactivation.
- Most significantly, the study discovered that a small protein alteration could drastically influence viral transcription processes, thereby opening up potential avenues for the development of new antiviral strategies.
Cite This Article
APA
Taube R, Fujinaga K, Irwin D, Wimmer J, Geyer M, Peterlin BM.
(2000).
Interactions between equine cyclin T1, Tat, and TAR are disrupted by a leucine-to-valine substitution found in human cyclin T1.
J Virol, 74(2), 892-898.
https://doi.org/10.1128/jvi.74.2.892-898.2000 Publication
Researcher Affiliations
- Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143-0703, USA.
MeSH Terms
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Base Sequence
- Cyclin T
- Cyclins / genetics
- Cyclins / isolation & purification
- Cyclins / metabolism
- Dogs
- Gene Products, tat / genetics
- Gene Products, tat / metabolism
- HeLa Cells
- Horses
- Humans
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / metabolism
- Leucine / genetics
- Leucine / metabolism
- Molecular Sequence Data
- Recombinant Fusion Proteins / genetics
- Recombinant Fusion Proteins / isolation & purification
- Recombinant Fusion Proteins / metabolism
- Response Elements
- Sequence Homology, Amino Acid
- Terminal Repeat Sequences
- Transcriptional Activation
- Valine / genetics
- Valine / metabolism
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