Cellular and viral specificity of equine infectious anemia virus Tat transactivation.
Abstract: Lentiviruses vary in their dependence on a functional tat gene during their viral life cycle. To begin to understand the viral and cellular parameters controlling equine infectious anemia virus (EIAV) transactivation, we investigated Tat function and Tat and LTR structural requirements necessary for successful transactivation. EIAV Tat expression was required for detection of viral antigens from a full-length provirus. The level of transactivation by EIAV Tat as measured by LTR-CAT assays correlated well with viral antigen expression. Using horse/mouse somatic cell hybrids (SCH), a single SCH line which supported EIAV transactivation was identified, indicating that the presence of specific horse chromosomes provided cellular factors required for transactivation. Transformed cell lines from several different species were also tested and found to differ in their ability to support EIAV transactivation. A canine cell line, Cf2Th, which was permissive for EIAV transactivation, and a human cell line, HeLa, which was not permissive for EIAV transactivation, were used to map regions of the LTR and Tat that were important in cell-specific transactivation. As expected, the R region of EIAV LTR was required for transactivation by EIAV Tat in all cell lines studied. Similarly, the R region of HIV LTR was necessary for transactivation by HIV Tat. However, the composition of the U3 region also influenced transactivation in a cell-specific manner. In Cf2Th cells, replacement of EIAV U3 sequences with HIV U3 sequences resulted in high basal (nontransactivated) expression, and as a result, only a twofold increase in expression was observed in the presence of EIAV Tat. Similar studies using HIV Tat demonstrated that transactivation occurred in Cf2Th cells when either EIAV or HIV U3 sequences were present in the LTR. In contrast, transactivation by either HIV or EIAV Tat in HeLa cells required the presence of HIV enhancer sequences. These findings suggested that the ability of transactivation to occur in some cell lines may involve interactions between cell-specific transcription factors and the activation domain of Tat. For transactivation in other cell lines, Tat appeared to require more ubiquitious factors that interact with both EIAV and HIV U3 sequences.
Publication Date: 1994-05-01 PubMed ID: 8178449DOI: 10.1006/viro.1994.1226Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research investigates the role and function of the Tat gene in the life cycle of equine infectious anemia virus (EIAV), along with the cellular and viral prerequisites for effective transactivation.
Understanding Tat Function and Requirements for Transactivation
- The study begins by studying the requirement of the Tat gene in the expression of viral antigens from a full-length provirus of EIAV. The researchers observed a direct relationship between the level of transactivation and viral antigen expression.
- To better understand the cellular factors influencing this process, they created horse/mouse somatic cell hybrids (SCH) and identified a single line that supported EIAV transactivation. This implied the presence of specific horse chromosomes, providing essential cellular factors for transactivation.
- The study also surveyed transformed cell lines from various species to determine their ability to support EIAV’s transactivation. The results varied across species.
Mapping Important LTR and Tat Regions
- A canine cell line (Cf2Th) that supported EIAV’s transactivation and a human cell line (HeLa) that did not were used to map the critical areas of LTR and Tat for cell-specific transactivation.
- As expected, the ‘R’ region of EIAV LTR was essential for EIAV Tat transactivation across all cell lines. Similarly, the ‘R’ region of HIV LTR was necessary for HIV Tat transactivation.
- The study also revealed that the composition of the ‘U3’ region impacted transactivation in a cell-specific manner.
Cell-Specific Interactions and their Roles
- In Cf2Th cells, the replacement of EIAV U3 sequences with HIV U3 sequences led to high basal (non-transactivated) expression. As a consequence, only a twofold increase in expression was observed when EIAV Tat was present.
- In contrast, for either HIV or EIAV Tat to transactivate in HeLa cells, the presence of HIV enhancer sequences was required. The team inferred that the ability to transactivate in some cell lines might involve interactions between cell-specific transcription factors and the activation domain of Tat.
- In other cell lines, however, Tat seemed to need more ubiquitous factors that interact with both EIAV and HIV U3 sequences for effective transactivation.
Cite This Article
APA
Maury WJ, Carpenter S, Graves K, Chesebro B.
(1994).
Cellular and viral specificity of equine infectious anemia virus Tat transactivation.
Virology, 200(2), 632-642.
https://doi.org/10.1006/viro.1994.1226 Publication
Researcher Affiliations
- LPVD, Rocky Mountain Laboratories, NIAID, Hamilton, Montana 59840.
MeSH Terms
- Animals
- Antigens, Viral / biosynthesis
- Base Sequence
- Cell Line
- Enhancer Elements, Genetic / genetics
- Gene Expression Regulation, Viral
- Gene Products, tat / genetics
- Gene Products, tat / metabolism
- Genes, tat / genetics
- Horses
- Humans
- Hybrid Cells
- Infectious Anemia Virus, Equine / genetics
- Mice
- Molecular Sequence Data
- Proviruses / genetics
- Recombinant Fusion Proteins / metabolism
- Repetitive Sequences, Nucleic Acid / genetics
- Species Specificity
- Transcription Factors / genetics
- Transcription Factors / metabolism
- Transcriptional Activation
Grant Funding
- AI 30025 / NIAID NIH HHS
Citations
This article has been cited 12 times.- Maury W, Price JP, Brindley MA, Oh C, Neighbors JD, Wiemer DF, Wills N, Carpenter S, Hauck C, Murphy P, Widrlechner MP, Delate K, Kumar G, Kraus GA, Rizshsky L, Nikolau B. Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum. Virol J 2009 Jul 13;6:101.
- Brindley MA, Widrlechner MP, McCoy JA, Murphy P, Hauck C, Rizshsky L, Nikolau B, Maury W. Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris. Virol J 2009 Jan 20;6:8.
- Brindley MA, Zhang B, Montelaro RC, Maury W. An equine infectious anemia virus variant superinfects cells through novel receptor interactions. J Virol 2008 Oct;82(19):9425-32.
- Brindley MA, Maury W. Equine infectious anemia virus entry occurs through clathrin-mediated endocytosis. J Virol 2008 Feb;82(4):1628-37.
- Bolinger C, Yilmaz A, Hartman TR, Kovacic MB, Fernandez S, Ye J, Forget M, Green PL, Boris-Lawrie K. RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1. Nucleic Acids Res 2007;35(8):2629-42.
- Brindley MA, Maury W. Endocytosis and a low-pH step are required for productive entry of equine infectious anemia virus. J Virol 2005 Dec;79(23):14482-8.
- Maury W, Thompson RJ, Jones Q, Bradley S, Denke T, Baccam P, Smazik M, Oaks JL. Evolution of the equine infectious anemia virus long terminal repeat during the alteration of cell tropism. J Virol 2005 May;79(9):5653-64.
- Hines R, Sorensen BR, Shea MA, Maury W. PU.1 binding to ets motifs within the equine infectious anemia virus long terminal repeat (LTR) enhancer: regulation of LTR activity and virus replication in macrophages. J Virol 2004 Apr;78(7):3407-18.
- Maury W, Wright PJ, Bradley S. Characterization of a cytolytic strain of equine infectious anemia virus. J Virol 2003 Feb;77(4):2385-99.
- Bieniasz PD, Grdina TA, Bogerd HP, Cullen BR. Highly divergent lentiviral Tat proteins activate viral gene expression by a common mechanism. Mol Cell Biol 1999 Jul;19(7):4592-9.
- Maury W, Oaks JL, Bradley S. Equine endothelial cells support productive infection of equine infectious anemia virus. J Virol 1998 Nov;72(11):9291-7.
- Maury W. Monocyte maturation controls expression of equine infectious anemia virus. J Virol 1994 Oct;68(10):6270-9.
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