Characterization of EIAV LTR variability and compartmentalization in various reservoir tissues of long-term inapparent carrier ponies.
Abstract: Dynamic genomic variation resulting in changes in envelope antigenicity has been established as a fundamental mechanism of persistence by equine infectious anemia virus (EIAV), as observed with other lentiviruses, including HIV-1. In addition to the reported changes in envelope sequences, however, certain studies indicate the viral LTR as a second variable EIAV gene, with the enhancer region being designated as hypervariable. These observations have lead to the suggestion that LTR variation may alter viral replication properties to optimize to the microenvironment of particular tissue reservoirs. To test this hypothesis directly, we examined the population of LTR quasispecies contained in various tissues of two inapparent carrier ponies experimentally infected with a reference EIAV biological clone for 18 months. The results of these studies demonstrated that the EIAV LTR is in fact highly conserved with respect to the infecting LTR species after 1.5 years of persistent infection and regardless of the tissue reservoir. Thus, these comprehensive analyses demonstrate for the first time that the EIAV LTR is highly conserved during long-term persistent infection and that the observed variations in viral LTR are associated more with in vitro adaptation to replication in cultured cells rather than in vivo replication in natural target cells.
Publication Date: 2003-07-02 PubMed ID: 12832214DOI: 10.1016/s0042-6822(03)00168-5Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research paper studies the behavior and variation of the equine infectious anemia virus (EIAV) in horses, and concludes that the virus remains largely consistent in various tissue reservoirs during long-term infection, contradicting the current understanding that it constantly adapts for optimization.
Overview of Research
- The research aims to understand the behavior of the EIAV lentivirus, particularly its long terminal repeat (LTR) gene region, when it enters different tissues within its horse hosts.
- The study investigates whether variation in the LTR region of EIAV causes changes in the virus’s replication to adapt to the specific environment of the infected tissues.
Research Methods
- Two undetected carrier ponies, that is, horses that carried the virus without showing symptoms, were artificially infected with an EIAV clone (a genetically identical sample).
- The LTR gene population in different tissues was studied, tracked, and compared over a period of 18 months.
Key Findings
- Contrary to the hypothesis, the research did not identify significant changes in the LTR region of EIAV, even after 1.5 years of infection.
- It was found that the EIAV LTR, instead of varying in different reservoirs, was highly conserved, which means it maintained its original composition and structure regardless of the tissue that it infected.
- The study concluded that variations observed in EIAV LTR may stem from adaptation to in vitro conditions (like cell cultures in a lab) rather than in vivo (within the animal).
Significance
- The research offers important insights into the behavior of EIAV, which can have implications for the understanding and treatment of other lentiviruses including HIV-1.
- By challenging the existing belief about the EIAV’s behavior within different tissue reservoirs, it prompts further investigation to gain a more accurate understanding of lentiviral behavior and persistence through genomic variation.
Cite This Article
APA
Reis JK, Craigo JK, Cook SJ, Issel CJ, Montelaro RC.
(2003).
Characterization of EIAV LTR variability and compartmentalization in various reservoir tissues of long-term inapparent carrier ponies.
Virology, 311(1), 169-180.
https://doi.org/10.1016/s0042-6822(03)00168-5 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
MeSH Terms
- Animals
- Base Sequence
- Bone Marrow / virology
- Carrier State / virology
- Cloning, Molecular
- Equine Infectious Anemia / virology
- Genetic Variation
- Horses
- Infectious Anemia Virus, Equine / genetics
- Kidney / virology
- Leukocytes, Mononuclear / virology
- Liver / virology
- Lymph Nodes / virology
- Molecular Sequence Data
- Sequence Alignment
- Spleen / virology
- Terminal Repeat Sequences
- Transcription Factors / genetics
Grant Funding
- 2 P41 RR06009 / NCRR NIH HHS
- 2R01 CA49296 / NCI NIH HHS
Citations
This article has been cited 3 times.- Wang XF, Liu Q, Wang YH, Wang S, Chen J, Lin YZ, Ma J, Zhou JH, Wang X. Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo. J Virol 2018 Apr 15;92(8).
- Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family. Retrovirology 2009 Oct 20;6:95.
- Maury W, Thompson RJ, Jones Q, Bradley S, Denke T, Baccam P, Smazik M, Oaks JL. Evolution of the equine infectious anemia virus long terminal repeat during the alteration of cell tropism. J Virol 2005 May;79(9):5653-64.
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