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Journal of virology1996; 70(6); 3346-3354; doi: 10.1128/JVI.70.6.3346-3354.1996

Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.

Abstract: Equine infectious anemia virus (EIAV) provides a uniquely dynamic system in which to study the mechanism and role of genomic variation in lentiviral persistence and pathogenesis. We have used a Shetland pony model of infection to investigate the association of specific long terminal repeat (LTR) and env gene genomic sequences with the initiation of infection and the onset of disease. We analyzed viral RNA isolated from a pathogenic stock of virus (EIAV PV) and from plasma taken during the first disease episode from two ponies infected with EIAV PV. Overall sequence variation within gp90 was low in EIAV PV and only slightly higher in plasma virus samples isolated from ponies during the first disease episode. However, a high proportion of mutations were localized to the principal neutralizing domain in EIAV PV and to the principal neutralizing domain and the gp90 hypervariable region in the two pony-derived samples. The rate of fixation of mutations was analyzed and determined to be approximately 4 x 10(-2) mutations per site per year. Sequence diversity within the U3 region of the LTR was extremely low, which suggested that the previously reported hypervariability of this region may be a consequence of selection for replication of EIAV in different host cells. The predominant EIAV PV env and LTR sequences were used to construct chimeric viruses so that the contribution of these sequences to viral pathogenicity could be examined. The chimeras replicated in cultured equine monocytes to the same extent as the parental nonpathogenic virus and did not cause disease in Shetland ponies by 120 days postinfection, suggesting that the EIAV genomic determinants of pathogenesis are complex.
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Publication Date: 1996-06-01 PubMed ID: 8648664PubMed Central: PMC190205DOI: 10.1128/JVI.70.6.3346-3354.1996Google Scholar: Lookup
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  • Non-U.S. Gov't
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  • U.S. Gov't
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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 looks into the role of genomic variation in the Equine infectious anemia virus (EIAV) during infection and early disease stages in ponies. A variety of gene sequences were analyzed and subsequent constructed chimeric virus, created from these sequences, did not cause illness in test subjects.

Understanding the Role of Genomic Variation

  • The Equine infectious anemia virus (EIAV) provides a useful system to study how genomic variation plays a part in persistence and pathogenesis of lentiviral diseases. These are slow-progressing diseases caused by lentiviruses, a family of retroviruses.
  • Through a model of infection in Shetland ponies, the researchers looked into the connection of specific gene sequences with the start of infection and early disease stages. Two critical gene sequences, the long terminal repeat (LTR) and the env, were at the center of this investigation.

Analysis of Viral RNA Sequences

  • An analysis was conducted on viral RNA, taken from a pathogenic EIAV stock and plasma samples from two ponies during the first disease episode after the infection.
  • The researchers observed that the overall variation within one of the env genes, the gp90, was low in the EIAV stock and a bit higher in the plasma virus samples from the ponies.
  • A significant number of mutations were seen in the principal neutralizing domain in the EIAV stock and in the same domain and gp90 hypervariable region in the pony samples.
  • The rate of mutation fixation was determined to be about 4 x 10(-2) mutations per site per year.

Sequence Diversity and Chimeric Viruses

  • The diversity level within the U3 region of the LTR was extremely low. It suggests that the previously mentioned hypervariable nature of this region might be due to selective replication of EIAV in various host cells.
  • The most prevalent EIAV env and LTR sequences were used in creating chimeric viruses for observing their contribution to disease causation.
  • The results showed that these chimeras replicated in cultivated equine monocytes to the same level as the parent nonpathogenic virus and did not result in disease in the ponies even by 120 days post-infection.

Conclusion

  • The research suggests that EIAV’s genomic traits that determine pathogenesis are complicated. This complexity highlights the need for further research and understanding.

Cite This Article

APA
Lichtenstein DL, Issel CJ, Montelaro RC. (1996). Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus. J Virol, 70(6), 3346-3354. https://doi.org/10.1128/JVI.70.6.3346-3354.1996

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 70
Issue: 6
Pages: 3346-3354

Researcher Affiliations

Lichtenstein, D L
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Issel, C J
    Montelaro, R C

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Base Sequence
      • Equine Infectious Anemia / virology
      • Genome, Viral
      • Horses
      • Infectious Anemia Virus, Equine / genetics
      • Molecular Sequence Data
      • Repetitive Sequences, Nucleic Acid
      • Viral Proteins / chemistry

      Grant Funding

      • 5R01CA49296 / NCI NIH HHS

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      Citations

      This article has been cited 18 times.
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