Naturally arising point mutations in non-essential domains of equine infectious anemia virus Rev alter Rev-dependent nuclear-export activity.
Abstract: Equine infectious anemia virus (EIAV) exhibits a high rate of genetic variation in vivo, and results in a clinically variable disease in infected horses. In vivo populations of EIAV have been characterized by the presence of distinct, genetic subpopulations of Rev that differ in phenotype and fluctuate in dominance in a manner coincident with each clinical stage of disease. This study examined the specific mutations that arose in vivo and altered the phenotype. The Rev protein was found to be highly conserved, and only 10 aa mutations were observed at a frequency greater than 10 % in the sample population. Nine of these mutations were capable of significantly altering Rev activity, either as single mutations in the context of the founder variant, or in the context of cumulatively fixed mutations. The results indicated that limited genetic variation outside the essential functional domains of Rev can alter the phenotype and may confer a selective advantage in vivo.
Publication Date: 2008-03-18 PubMed ID: 18343848PubMed Central: PMC4425282DOI: 10.1099/vir.0.83195-0Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The study investigates how small genetic changes, or mutations, in the equine infectious anemia virus (EIAV) can significantly affect the virus’s activity. Also, it explored how these changes might provide benefits in a living organism.
Introduction and Background
- The virus in focus, EIAV, is known to rapidly mutate and cause varying degrees of disease in horses.
- The researchers were particularly interested in different subpopulations of the protein Rev that exist within EIAV, which grow and decrease based on the stage of the disease.
Mutation Analysis and Phenotype Alterations
- The researchers examined which specific mutations occurred naturally and how these changes affected the virus’s behavior or phenotype.
- The Rev protein, of interest to the researchers, was highly similar across different virus samples.
- Of all the observed genetic changes, only ten affected more than 10% of the total viral sample.
- Nine out of these ten changes had a noticeable effect on the Rev protein activity. This observable change was either as singular mutations in the initial type of the virus or in the context of mutations building up over time.
Consequences of Genetic Variation
- The findings indicated that even minor genetic variations that do not touch Rev’s crucial operational domains can indeed change its phenotype.
- This shift in phenotype, brought by limited genetic variations, might offer a selective advantage to the virus in a natural, non lab-involved environment.
Implication
- Understanding these selective mutations and their effect on the phenotype behavior can potentially help in developing better therapeutic strategies against EIAV.
Cite This Article
APA
Sparks WO, Dorman KS, Liu S, Carpenter S.
(2008).
Naturally arising point mutations in non-essential domains of equine infectious anemia virus Rev alter Rev-dependent nuclear-export activity.
J Gen Virol, 89(Pt 4), 1043-1048.
https://doi.org/10.1099/vir.0.83195-0 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011, USA.
- Department of Statistics, Iowa State University, Ames, IA 50011, USA.
- Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011, USA.
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011, USA.
MeSH Terms
- Active Transport, Cell Nucleus
- Animals
- Cell Nucleus / metabolism
- Equine Infectious Anemia / virology
- Gene Products, rev / genetics
- Gene Products, rev / metabolism
- Horses
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / metabolism
- Point Mutation
- Protein Structure, Tertiary / genetics
Grant Funding
- R01 CA128568 / NCI NIH HHS
- R01 CA128568-01A2 / NCI NIH HHS
- R21 CA097936 / NCI NIH HHS
- CA97936 / NCI NIH HHS
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Citations
This article has been cited 6 times.- Jackson PEH, Dzhivhuho G, Rekosh D, Hammarskjold ML. Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis.. Curr HIV Res 2020;18(2):85-98.
- Fernandes JD, Booth DS, Frankel AD. A structurally plastic ribonucleoprotein complex mediates post-transcriptional gene regulation in HIV-1.. Wiley Interdiscip Rev RNA 2016 Jul;7(4):470-86.
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