Long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.
Abstract: The Wyoming strain of equine infectious anaemia virus (EIAV) is a highly virulent field strain that replicates to high titre in vitro only in primary equine monocyte-derived macrophages. In contrast, Wyoming-derived fibroblast-adapted EIAV strains (Malmquist virus) replicate in primary foetal equine kidney and equine dermis cells as well as in the cell lines FEA and Cf2Th. Wyoming and Malmquist viruses differ extensively both in long terminal repeat (LTR) and envelope region sequences. We have compared the promoter activities of the Wyoming LTR with those of LTRs derived from fibroblast-adapted viruses by examining their abilities to drive a luciferase reporter gene as well as by construction of infectious molecular clones differing only in LTR sequence. Our results indicate that LTR sequences are a major restriction for growth of the Wyoming strain of EIAV in fibroblasts.
Publication Date: 1999-03-26 PubMed ID: 10092016DOI: 10.1099/0022-1317-80-3-755Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This study examines the role of long terminal repeat sequences in determining the specific type of cells (cell tropism) viruses, specifically the equine infectious anaemia virus, can infect.
Understanding the Virus
- The research focuses on the Wyoming strain of equine infectious anaemia virus (EIAV), known for its virulence and selective replication, only in equine monocyte-derived macrophages in in-vitro conditions.
- In contrast, strains of the same virus adapted to fibroblasts, known as the Malmquist virus, can replicate in a wider variety of cells, including primary foetal equine kidney cells, equine dermis cells, and the FEA and Cf2Th cell lines.
Genetic Differences between Viral Strains
- The Wyoming and Malmquist viruses are largely different in their long terminal repeat (LTR) and envelope region sequences. The LTR is a sequence in the DNA of retroviruses involved in the integration of the viral genome into the host cell’s genome.
- LTRs also play a crucial role in controlling viral gene expression.
Comparing Promoter Activities of LTRs
- This research compared the promoter activities of the Wyoming LTR with LTRs derived from fibroblast-adapted viruses to understand their role in determining cell tropism.
- The experimentation involved examining the ability of these LTRs to drive a luciferase reporter gene, as well as constructing infectious molecular clones that only differed in their LTR sequences.
Findings and Conclusion
- The results from the research suggest that LTR sequences are a crucial factor restricting the Wyoming strain of EIAV from growing in fibroblasts.
- This finding shows that LTRs have a significant role in defining the cell tropism of this particular virus, indicating potential areas of further research and development regarding viral infections and treatments.
Cite This Article
APA
Payne SL, La Celle K, Pei XF, Qi XM, Shao H, Steagall WK, Perry S, Fuller F.
(1999).
Long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.
J Gen Virol, 80 ( Pt 3), 755-759.
https://doi.org/10.1099/0022-1317-80-3-755 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Base Sequence
- Cell Line
- Consensus Sequence / genetics
- Fibroblasts / virology
- Gene Expression Regulation, Viral
- Gene Products, tat / genetics
- Gene Products, tat / metabolism
- Genes, Reporter
- Genetic Variation
- Horses / virology
- Infectious Anemia Virus, Equine / classification
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / growth & development
- Infectious Anemia Virus, Equine / pathogenicity
- Macrophages / virology
- Molecular Sequence Data
- Mutagenesis, Site-Directed
- Promoter Regions, Genetic / genetics
- Terminal Repeat Sequences / genetics
- Transcriptional Activation
- Transfection
- Wyoming
Grant Funding
- CA-50168 / NCI NIH HHS
Citations
This article has been cited 11 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.
- 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).
- Liu Q, Ma J, Wang XF, Xiao F, Li LJ, Zhang JE, Lin YZ, Du C, He XJ, Wang X, Zhou JH. Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. Vet Immunol Immunopathol 2016 Feb;170:30-40.
- Cervantes DT, Ball JM, Edwards J, Payne S. Horses naturally infected with EIAV harbor 2 distinct SU populations but are monophyletic with respect to IN. Virus Genes 2016 Feb;52(1):71-80.
- Patel JR, Heldens JG, Bakonyi T, Rusvai M. Important mammalian veterinary viral immunodiseases and their control. Vaccine 2012 Feb 27;30(10):1767-81.
- Blackard JT, Ma G, Welge JA, Martin CM, Sherman KE, Taylor LE, Mayer KH, Jamieson DJ. Analysis of a non-structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization. J Med Virol 2012 Feb;84(2):242-52.
- 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.
- Oskarsson T, Hreggvidsdóttir HS, Agnarsdóttir G, Matthíasdóttir S, Ogmundsdóttir MH, Jónsson SR, Georgsson G, Ingvarsson S, Andrésson OS, Andrésdóttir V. Duplicated sequence motif in the long terminal repeat of maedi-visna virus extends cell tropism and is associated with neurovirulence. J Virol 2007 Apr;81(8):4052-7.
- Zhang B, Jin S, Jin J, Li F, Montelaro RC. A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus. Proc Natl Acad Sci U S A 2005 Jul 12;102(28):9918-23.
- 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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