Effects of long terminal repeat sequence variation on equine infectious anemia virus replication in vitro and in vivo.
Abstract: The long terminal repeat (LTR) is reported to be one of the most variable portions of the equine infectious anemia virus (EIAV) genome. To date, however, no information is available on the effects of observed sequence variations on viral replication properties, despite a widespread assumption of the biological importance of EIAV LTR variation. EIAV LTR sequence variability is confined mostly to a small portion of the enhancer within the U3 segment of the LTR. Analysis of published EIAV LTR sequences revealed six different types of LTR based on the pattern of putative transcription factor motifs within the variable region of the enhancer. To test directly the significance of LTR variation, the in vitro and in vivo replication properties of two variant LTR species were investigated using two isogenic viruses, EIAV(19-2) and EIAV(19-2-6A), differing only within the enhancer region. The results of these studies demonstrated that the two variants replicated with similar kinetics and to equal levels in cultured equine fibroblasts or in equine macrophage, the natural target cell of EIAV, even after prolonged serial passage in the latter cell type. Furthermore, EIAV(19-2) and EIAV(19-2-6A) variants demonstrated similar replication levels in experimentally infected ponies. However, ponies infected with EIAV(19-2-6A) exhibited a rapid switch in the prevalent LTR type, such that by 112 days postinfection, no original-LTR-type viruses were evident. This specific and rapid shift in LTR quasispecies indicates an in vivo selection that is not reflected in simple in vitro replication rates, suggesting undefined selection pressures in vivo that drive LTR variation during persistent EIAV infection.
Copyright 1999 Academic Press.
Publication Date: 1999-11-02 PubMed ID: 10544113DOI: 10.1006/viro.1999.9921Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates the impacts of sequence variation in the long terminal repeat (LTR) region of the equine infectious anemia virus (EIAV) on the virus’s replication in both a controlled environment and within a living organism. The findings suggest that while such variations didn’t notably affect in vitro replication rates, they do seem to influence selection pressures that drive LTR variation during EIAV persistent infection in living organisms.
EIAV LTR Sequence Variation
- The long terminal repeat (LTR) is known to be one of the most variable parts of the EIAV genome, yet prior to this study, its effects on viral replication were unknown.
- Most of the variation in the EIAV LTR sequences is located within a small portion of the enhancer in the U3 segment of the LTR.
- An analysis of existing EIAV LTR sequences revealed the presence of six different types of LTRs, determined by the pattern of putative transcription factor motifs within the variable region of the enhancer.
Investigation of LTR Variation Effects on EIAV Replication
- In this study, the researchers tested the impact of LTR variation on EIAV replication using two isogenic viruses, EIAV(19-2) and EIAV(19-2-6A), which differ only in the enhancer region.
- These viruses were observed to replicate with similar kinetics and to equal levels in both cultured equine fibroblasts and equine macrophage, which is the natural target cell of EIAV, even after repeated serial passage in the latter cell type.
Impact of LTR Variation in Experimentally Infected Ponies
- The same variants were also tested in experimentally infected ponies, wherein both demonstrated similar replication levels.
- However, there was a significant observation that ponies infected with EIAV(19-2-6A) displayed a quick change in the prevalent LTR type. By the 112th day post-infection, no traces of the original-LTR-type viruses were found.
- This suggests an in vivo selection process that is not reflected in in vitro replication rates, alluding to undisclosed selection pressures in vivo that perpetuate LTR variation during a persistent EIAV infection.
Cite This Article
APA
Lichtenstein DL, Craigo JK, Leroux C, Rushlow KE, Cook RF, Cook SJ, Issel CJ, Montelaro RC.
(1999).
Effects of long terminal repeat sequence variation on equine infectious anemia virus replication in vitro and in vivo.
Virology, 263(2), 408-417.
https://doi.org/10.1006/viro.1999.9921 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
MeSH Terms
- Animals
- Base Sequence
- Cell Line
- Enhancer Elements, Genetic / genetics
- Equine Infectious Anemia / blood
- Equine Infectious Anemia / virology
- Fibroblasts / virology
- Genetic Variation / genetics
- Genetic Variation / physiology
- Horses / virology
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / growth & development
- Infectious Anemia Virus, Equine / pathogenicity
- Macrophages / virology
- Molecular Sequence Data
- Mutation / genetics
- RNA, Viral / analysis
- RNA, Viral / genetics
- Response Elements / genetics
- Selection, Genetic
- Serial Passage
- Terminal Repeat Sequences / genetics
- Terminal Repeat Sequences / physiology
- Transcription Factors / metabolism
- Viremia / blood
- Viremia / virology
- Virus Replication / genetics
Grant Funding
- R01 CA49296 / NCI NIH HHS
Citations
This article has been cited 6 times.- Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China. Oncotarget 2018 Jan 2;9(1):1356-1364.
- Eckstrand CD, Castillo D, McDonnel SJ, Hillman CN, Vapniarsky N, Shanthalingam S, de las Heras M, Murphy BG. Genetic variability and in vitro transcriptional permissibility of primary ovine beta-retrovirus promoter isolates. Am J Vet Res 2013 Nov;74(11):1421-7.
- Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13. Virus Genes 2010 Aug;41(1):86-98.
- 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.
- Payne SL, Pei XF, Jia B, Fagerness A, Fuller FJ. Influence of long terminal repeat and env on the virulence phenotype of equine infectious anemia virus. J Virol 2004 Mar;78(5):2478-85.
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