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Home / Equine Research Bank / J Virol / Evolution of the equine infectious anemia virus long termina...
Journal of virology2005; 79(9); 5653-5664; doi: 10.1128/JVI.79.9.5653-5664.2005

Evolution of the equine infectious anemia virus long terminal repeat during the alteration of cell tropism.

Abstract: Equine infectious anemia virus (EIAV) is a lentivirus with in vivo cell tropism primarily for tissue macrophages; however, in vitro the virus can be adapted to fibroblasts and other cell types. Tropism adaptation is associated with both envelope and long terminal repeat (LTR) changes, and findings strongly suggest that these regions of the genome influence cell tropism and virulence. Furthermore, high levels of genetic variation have been well documented in both of these genomic regions. However, specific EIAV nucleotide or amino acid changes that are responsible for cell tropism changes have not been identified. A study was undertaken with the highly virulent, macrophage-tropic strain of virus EIAV(wyo) to identify LTR changes associated with alterations in cell tropism. We found the stepwise generation of a new transcription factor binding motif within the enhancer that was associated with adaptation of EIAV to endothelial cells and fibroblasts. An LTR that contained the new motif had enhanced transcriptional activity in fibroblasts, whereas the new site did not alter LTR activity in a macrophage cell line. This finding supports a previous prediction that selection for new LTR genetic variants may be a consequence of cell-specific selective pressures. Additional investigations of the EIAV(wyo) LTR were performed in vivo to determine if LTR evolution could be detected over the course of a 3-year infection. Consistent with previous in vivo findings, we observed no changes in the enhancer region of the LTR over that time period, indicating that the EIAV(wyo) LTR was evolutionarily stable in vivo.
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Publication Date: 2005-04-14 PubMed ID: 15827180PubMed Central: PMC1082720DOI: 10.1128/JVI.79.9.5653-5664.2005Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the changes in the Equine Infectious Anemia Virus (EIAV) when it adapts to different cell types, with a specific focus on how the ‘long terminal repeat’ (LTR) region of the virus’ genetics changes in this process.

Understanding EIAV and Cell Tropism

  • Equine infectious anemia virus (EIAV) is a type of lentivirus which primarily targets tissue macrophages in vivo – meaning within a living organism.
  • In a lab setting, EIAV can adapt to various cell types, such as fibroblasts – which are cells that produce connective tissue.
  • The adaptation of EIAV to different cell types, known as ‘cell tropism’, is associated with changes in both the envelope of the virus and the long terminal repeat (LTR) – which are repetitive DNA sequences at each end of a viral genome.
  • These adaptations have not yet been tied to any specific genetic sequences or protein changes.

The Study and its Findings

  • The study aimed to identify the changes in the LTR that are associated with how the virus alters its cell tropism.
  • They used a highly virulent, strain of the virus, EIAV(wyo), which primarily targets macrophages.
  • The researchers discovered that when adapting to endothelial cells (which line the inside of blood vessels) and fibroblasts, there was a stepwise creation of a new transcription factor binding motif within the LTR enhancer, which is a sequence of DNA that helps initiate transcription of a particular gene.
  • An LTR containing this new motif demonstrated enhanced transcriptional activity in fibroblasts, however this new binding site did not change the activity of the LTR in a macrophage cell line.
  • This supports the theory that the selection for genetic alterations in the LTR region might be a result of pressures from the specific cells that the virus infects.
  • They also examined the LTR of the EIAV(wyo) strain in vivo over a 3-year infection period to see how it evolved, and found that there were no changes in the enhancer region of the LTR, suggesting that this region is stable over time within a living organism.

Cite This Article

APA
Maury W, Thompson RJ, Jones Q, Bradley S, Denke T, Baccam P, Smazik M, Oaks JL. (2005). Evolution of the equine infectious anemia virus long terminal repeat during the alteration of cell tropism. J Virol, 79(9), 5653-5664. https://doi.org/10.1128/JVI.79.9.5653-5664.2005

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 79
Issue: 9
Pages: 5653-5664

Researcher Affiliations

Maury, Wendy
  • Department of Microbiology, 3403 Bowen Science Building, University of Iowa, Iowa City, IA 52242-1109, USA. wendy-maury@uiowa.edu
Thompson, Robert J
    Jones, Quentin
      Bradley, Sarahann
        Denke, Tara
          Baccam, Prasith
            Smazik, Matthew
              Oaks, J Lindsay

                MeSH Terms

                • Adaptation, Physiological
                • Amino Acid Motifs
                • Animals
                • Base Sequence
                • Biological Evolution
                • Cells, Cultured
                • Disease Models, Animal
                • Endothelial Cells
                • Enhancer Elements, Genetic / genetics
                • Equine Infectious Anemia / virology
                • Fibroblasts
                • Horses
                • Infectious Anemia Virus, Equine / genetics
                • Infectious Anemia Virus, Equine / pathogenicity
                • Macrophages
                • Molecular Sequence Data
                • Sequence Alignment
                • Serial Passage
                • Terminal Repeat Sequences / genetics
                • Virulence / genetics

                Grant Funding

                • AI144638 / NIAID NIH HHS
                • CA72063 / NCI NIH HHS

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                Citations

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