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Virology1996; 225(2); 395-399; doi: 10.1006/viro.1996.0614

Analysis of the long terminal repeat from a cytopathic strain of equine infectious anemia virus.

Abstract: Sequential passage of the tissue culture-adapted prototype strain of EIAV in fetal donkey dermal (FDD) cell cultures generated a virus stock which exhibits cytopathic effects in FDD cell cultures. In this study, the effects of the long terminal repeat (LTR) region on virus replication and cytopathogenicity were examined. The FDD-adapted virus LTR was found to contain a number of base pair mutations and a large insertion within the U3 region in comparison with the previously characterized LTR, lambda12. Transient gene expression studies showed that basal promoter activity, in FDD cell cultures, of the FDD-adapted virus LTR was more than seven times greater than that of lambda12. Analysis of an infectious EIAV molecular clone in which the LTR region was replaced with the corresponding region of FDD-adapted virus showed that the LTR increased replication capacity but did not influence cytopathogenicity.
Publication Date: 1996-11-15 PubMed ID: 8918926DOI: 10.1006/viro.1996.0614Google 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 paper explores how slight genetic changes in the equine infectious anemia virus (EIAV) can affect how much harm the virus causes (cytopathogenicity) and how quickly it reproduces (replication). The results indicate that while such mutations can boost replication, they don’t significantly affect cytopathogenicity.

Research Background

  • The team studied the equine infectious anemia virus (EIAV), a disease affecting horses that’s similar to HIV in humans.
  • They developed a modified strain of the virus by continually growing it in fetal donkey dermal (FDD) cell cultures, which resulted in a virus form that causes cells to break down and die—i.e., it shows cytopathogenic effects.
  • The research’s prime focus was the long terminal repeat (LTR) region of the virus—sequences at each end of the viral RNA that control gene expression and integration into the host DNA.

Key Findings

  • The LTR of this modified EIAV strain had several base pair mutations and a significant insertion within the U3 region, differing from the previously studied LTR, termed lambda12.
  • This modified LTR showed over seven times the basal promoter activity (i.e., it was seven times more effective in initiating transcription, the first step of gene expression) in FDD cell cultures than lambda12.
  • The researchers then created a cloned form of the virus, replacing the original LTR with the FDD-adapted LTR, and found it had a much higher replication capacity, meaning that it could reproduce much quicker.
  • However, these changes didn’t make the virus any more cytopathogenic—the modified strain didn’t cause cell death any more effectively than the original version.

Implications of the Study

  • The findings suggest that mutations in the LTR region can increase the replication rate of EIAV, potentially making it more transmissible.
  • Despite the higher replication rate, these mutations didn’t affect the virus’s cytopathogenicity, implying that alterations to the LTR don’t necessarily make EIAV more harmful.
  • Such insights could have broader applications in understanding and combating viral diseases, particularly those that bear similar retroviral characteristics, such as HIV in humans.

Cite This Article

APA
Madden CR, Shih DS. (1996). Analysis of the long terminal repeat from a cytopathic strain of equine infectious anemia virus. Virology, 225(2), 395-399. https://doi.org/10.1006/viro.1996.0614

Publication

ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 225
Issue: 2
Pages: 395-399

Researcher Affiliations

Madden, C R
  • Department of Biochemistry, Louisiana State University, Baton Rouge 70803, USA.
Shih, D S

    MeSH Terms

    • Animals
    • Base Sequence
    • Cell Line
    • Cytopathogenic Effect, Viral / genetics
    • Genes, Viral
    • Infectious Anemia Virus, Equine / physiology
    • Molecular Sequence Data
    • Mutation
    • Repetitive Sequences, Nucleic Acid
    • Sequence Alignment
    • Virus Replication / genetics

    Grant Funding

    • CA-49296 / NCI NIH HHS

    Citations

    This article has been cited 4 times.
    1. Wei L, Fan X, Lu X, Zhao L, Xiang W, Zhang X, Xue F, Shao Y, Shen R, Wang X. Genetic variation in the long terminal repeat associated with the transition of Chinese equine infectious anemia virus from virulence to avirulence.. Virus Genes 2009 Apr;38(2):285-8.
      doi: 10.1007/s11262-008-0317-ypubmed: 19130201google scholar: lookup
    2. 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.
    3. Diaz-Griffero F, Hoschander SA, Brojatsch J. Bystander killing during avian leukosis virus subgroup B infection requires TVB(S3) signaling.. J Virol 2003 Dec;77(23):12552-61.
    4. Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.. J Virol 1998 Feb;72(2):1383-93.