Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism

Wendy Maury; Robert J Thompson; Quentin Jones; Sarahann Bradley; Tara Denke; Prasith Baccam; Matthew Smazik; J. Lindsay Oaks

doi:10.1128/JVI.79.9.5653-5664.2005

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Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism

Journal article

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Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism

Wendy Maury, Robert J Thompson, Quentin Jones, Sarahann Bradley, Tara Denke, Prasith Baccam, Matthew Smazik and J. Lindsay Oaks

Journal of virology, Vol.79(9), pp.5653-5664

05/2005

DOI: 10.1128/JVI.79.9.5653-5664.2005

PMCID: PMC1082720

PMID: 15827180

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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.

Virus-Cell Interactions

Details

Title: Subtitle: Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism
Creators: Wendy Maury - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Robert J Thompson - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Quentin Jones - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Sarahann Bradley - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Tara Denke - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Prasith Baccam - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Matthew Smazik - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
J. Lindsay Oaks - Department of Microbiology, University of Iowa, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: Journal of virology, Vol.79(9), pp.5653-5664
DOI: 10.1128/JVI.79.9.5653-5664.2005
PMID: 15827180
PMCID: PMC1082720
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 05/2005
Academic Unit: Microbiology and Immunology; Operative Dentistry
Record Identifier: 9984083891102771

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