Genetic and biological variation in equine infectious anemia virus Rev correlates with variable stages of clinical disease in an experimentally infected pony.
Abstract: Genetic and biological variation in the regulatory protein Rev of equine infectious anemia virus (EIAV) were examined throughout a clinically dynamic disease course of an experimentally infected pony. Following infection with the virulent EIAV(Wyo), the pony underwent a variable disease course, including an acute fever episode at 12 days postinfection (DPI), multiple recurrent fever episodes until 135 DPI, a prolonged subclinical period, and two late fever episodes. Viral RNA was isolated from the inoculum and sequential sera samples, and the rev exon 2/gp45 overlapping ORFs were amplified, cloned, and sequenced. Novel variants were found throughout infection, and genetic analyses indicated that both the Rev and gp45 ORFs were under selective pressure. The Rev variant predominant in the inoculum, R1, remained predominant during the early periods following infection (until 35 DPI); however, R1 was replaced by new predominant variants during the recurrent fever period (67-135 DPI). R1 reemerged as the predominant variant during the afebrile period, but a new predominant variant, R93, was associated with the late fever episodes. Rev variants predominant during recurrent febrile and late-febrile periods had significantly higher Rev-mediated nuclear export activity than the variants predominant during the acute and afebrile periods. Statistical correlation was found between Rev activity and different stages of clinical disease. Together, these results suggest that genetic and biological variation in rev may be a contributing factor in EIAV disease progression.
Copyright 2001 Academic Press.
Publication Date: 2001-01-09 PubMed ID: 11145901DOI: 10.1006/viro.2000.0696Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research examined changes in the genetic and biological characteristics of a protein in the equine infectious anemia virus throughout different stages of the disease in an intentionally infected pony. The findings suggest that these changes might have a role in driving the disease’s progression.
Background and Purpose
- The study was aimed at exploring the genetic and biological variations in a protein called Rev of the Equine Infectious Anemia Virus (EIAV), a lentivirus that causes anemia, intermittent fever, and other severe symptoms in horses.
- The researchers were particularly interested in evaluating these changes throughout different stages of the disease in a pony that was experimentally infected with a strain of the virus known as EIAV(Wyo).
- The primary hypothesis was that the genetic and biological variations in the Rev protein could potentially contribute to the progression of the disease.
Research Methodology
- The pony was infected with the EIAV virus and meticulously monitored through its different disease stages, which included an acute fever, several recurrent fever episodes, a prolonged symptomless period, and late fever episodes.
- The viral RNA was extracted from the initial infection agent and sequential blood samples and the overlapping open reading frames (ORFs) for the second exon of rev and the protein gp45 were amplified, cloned, and sequenced.
- Genetic analyses were conducted on these sequences to identify novel variants and to examine the selective pressures on both the Rev and gp45 proteins.
Findings and Conclusions
- The inoculum’s predominant Rev variant, R1, remained dominant during the early post-infection stages up to the 35th day of infection.
- R1 was displaced by new predominant variants during the recurrent fever period (from day 67 to 135 of infection).
- However, R1 resurfaced as the dominant variant during the fever-free periods, but a new predominant variant, R93, was associated with the late fever episodes.
- Rev variants that were dominant during recurrent fever and late fever stages demonstrated higher nuclear export activity mediated by Rev than the variants dominant during the acute and symptom-free periods.
- A statistical correlation was established between Rev activity and the different disease stages, implicating genetic and biological variation in the Rev protein as a potential contributory factor to EIAV disease progression.
Cite This Article
APA
Belshan M, Baccam P, Oaks JL, Sponseller BA, Murphy SC, Cornette J, Carpenter S.
(2001).
Genetic and biological variation in equine infectious anemia virus Rev correlates with variable stages of clinical disease in an experimentally infected pony.
Virology, 279(1), 185-200.
https://doi.org/10.1006/viro.2000.0696 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa, 50011, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Equine Infectious Anemia / physiopathology
- Equine Infectious Anemia / virology
- Evolution, Molecular
- Gene Products, rev / chemistry
- Gene Products, rev / genetics
- Gene Products, rev / metabolism
- Genetic Variation
- Horses
- Infectious Anemia Virus, Equine / classification
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / pathogenicity
- Infectious Anemia Virus, Equine / physiology
- Molecular Sequence Data
- RNA, Viral / blood
- Sequence Analysis, DNA
- Viral Envelope Proteins / chemistry
- Viral Envelope Proteins / genetics
- Viral Load
- Virulence
Grant Funding
- R01 AI 44638 / NIAID NIH HHS
Citations
This article has been cited 24 times.- Jackson PEH, Holsey J, Turse L, Hammarskjold ML, Rekosh D. Rev-Rev Response Element Activity Selection Bias at the HIV Transmission Bottleneck.. bioRxiv 2023 Apr 5;.
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