Analyze Diet
Journal of virology1997; 71(7); 5031-5039; doi: 10.1128/JVI.71.7.5031-5039.1997

In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

Abstract: Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this study, we further characterized the PND of virus isolates sequentially recovered during 22 febrile episodes in seven horses newly infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA clones derived from the 22 episodes confirmed the generation of various new viral quasispecies with insertions/duplications in the PND. Although the insertion/duplication sequences in a total of 92 cDNA clones were extensively heterogeneous, we hypothesized that all the insertions/duplications occurred during reverse transcription from viral genomic RNA to minus strand DNA. The insertion/duplication regions were derived from a part of the PND sequence, which consisted of five small units. These small units, some with various substitutions and/or deletions, were also generated, especially in regions with insertions/duplications. Of particular note was that all these virus variants, except for two cDNA variants, were generated by essentially four different duplication pathways. Thus, these results extend the significance of insertions/duplications in the PND to the novel generation of EIAV in vivo during febrile episodes.
Publication Date: 1997-07-01 PubMed ID: 9188568PubMed Central: PMC191736DOI: 10.1128/JVI.71.7.5031-5039.1997Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates how the Equine Infectious Anemia Virus (EIAV) evolves and adapts in horses, specifically during febrile episodes. The study discovered that the virus generates new variations through genetic changes in a portion of its sequence related to immune system recognition.

Research Background and Methodology

  • The focus of this research is the Equine Infectious Anemia Virus (EIAV), which serves as a model for studying how retroviruses evade the immune system by generating variant clones.
  • Previously, the researchers had sequenced the gp90-encoding region of 22 cDNA clones from five distinct EIAV isolates. The results suggested changes within the virus’s Principal Neutralizing Domain (PND), a key area recognized by the immune system, were due to insertions/duplications of genetic material.
  • In this study, they extended their research, examining new infections caused by a virulent EIAV strain known as V70 in seven horses.
  • The team studied 22 febrile (feverish) episodes in these horses, sequencing 70 cDNA clones from these infections.

Results and Interpretation

  • The researchers’ sequencing confirmed that the EIAV virus was generating “quasispecies,” or new viral variants, through insertions/duplications in its PND.
  • These sequences were highly varied, but the researchers hypothesized they all resulted from the reverse transcription process, as the viral RNA is turned into DNA.
  • These insertion/duplication regions corresponded with part of the original PND sequence, consisting of five small units. Some of these units exhibited substitutions or deletions, particularly in regions with insertions/duplications.
  • All of these virus variants (apart from two cDNA variants) resulted from four different pathways of duplication.
  • This study thereby emphasizes the importance of these insertions/duplications in the PND, as it contributes to the creation of new EIAV variants in horses during fever episodes.

Implications and Significance of the Study

  • The findings of this research are important as they show the complexity and adaptability of EIAV, and by implication, other similar retroviruses.
  • The ability of the virus to modify its Principal Neutralizing Domain through insertions/duplications enables it to evade the host immune defenses, leading to persistent infection and increased viral diversity.
  • This study serves as a crucial step in understanding the mechanisms through which retroviruses generate variants and adapt themselves, further contributing to the scientific understanding of virus-host dynamics.

Cite This Article

APA
Zheng YH, Sentsui H, Nakaya T, Kono Y, Ikuta K. (1997). In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain. J Virol, 71(7), 5031-5039. https://doi.org/10.1128/JVI.71.7.5031-5039.1997

Publication

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 71
Issue: 7
Pages: 5031-5039

Researcher Affiliations

Zheng, Y H
  • Section of Serology, Institute of Immunological Science, Hokkaido University, Kita-ku, Sapporo, Japan.
Sentsui, H
    Nakaya, T
      Kono, Y
        Ikuta, K

          MeSH Terms

          • Amino Acid Sequence
          • Animals
          • Base Sequence
          • DNA, Viral
          • Fever / virology
          • Genetic Variation
          • Glycoproteins
          • Horses
          • Infectious Anemia Virus, Equine / genetics
          • Infectious Anemia Virus, Equine / isolation & purification
          • Infectious Anemia Virus, Equine / pathogenicity
          • Molecular Sequence Data
          • Mutagenesis
          • Neutralization Tests
          • Sequence Analysis, DNA
          • Sequence Homology, Amino Acid
          • Sequence Homology, Nucleic Acid
          • Viral Envelope Proteins / genetics
          • Virulence

          References

          This article includes 37 references
          1. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.. J Virol 1994 Jul;68(7):4650-5.
          2. Temin HM. Retrovirus variation and reverse transcription: abnormal strand transfers result in retrovirus genetic variation.. Proc Natl Acad Sci U S A 1993 Aug 1;90(15):6900-3.
            pubmed: 7688465doi: 10.1073/pnas.90.15.6900google scholar: lookup
          3. Sellon DC, Fuller FJ, McGuire TC. The immunopathogenesis of equine infectious anemia virus.. Virus Res 1994 May;32(2):111-38.
            pubmed: 8067050doi: 10.1016/0168-1702(94)90038-8google scholar: lookup
          4. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH. Viral dynamics in human immunodeficiency virus type 1 infection.. Nature 1995 Jan 12;373(6510):117-22.
            pubmed: 7529365doi: 10.1038/373117a0google scholar: lookup
          5. Michael NL, Mo T, Merzouki A, O'Shaughnessy M, Oster C, Burke DS, Redfield RR, Birx DL, Cassol SA. Human immunodeficiency virus type 1 cellular RNA load and splicing patterns predict disease progression in a longitudinally studied cohort.. J Virol 1995 Mar;69(3):1868-77.
          6. Tao B, Fultz PN. Molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, SIVsmmPBj14.. J Virol 1995 Apr;69(4):2031-7.
          7. Cao Y, Ho DD, Todd J, Kokka R, Urdea M, Lifson JD, Piatak M Jr, Chen S, Hahn BH, Saag MS. Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma.. AIDS Res Hum Retroviruses 1995 Mar;11(3):353-61.
            pubmed: 7786581doi: 10.1089/aid.1995.11.353google scholar: lookup
          8. Kishi M, Zheng YH, Bahmani MK, Tokunaga K, Takahashi H, Kakinuma M, Lai PK, Nonoyama M, Luftig RB, Ikuta K. Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells.. J Virol 1995 Dec;69(12):7507-18.
          9. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time.. Science 1996 Mar 15;271(5255):1582-6.
            pubmed: 8599114doi: 10.1126/science.271.5255.1582google scholar: lookup
          10. Lichtenstein DL, Issel CJ, Montelaro RC. Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.. J Virol 1996 Jun;70(6):3346-54.
          11. Palaniappan C, Wisniewski M, Wu W, Fay PJ, Bambara RA. Misincorporation by HIV-1 reverse transcriptase promotes recombination via strand transfer synthesis.. J Biol Chem 1996 Sep 13;271(37):22331-8.
            pubmed: 8798393doi: 10.1074/jbc.271.37.22331google scholar: lookup
          12. Nakaya T, Fujinaga K, Doi H, Suzuki S, Takahashi H, Nishino Y, Kishi M, Azuma I, Luftig RB, Ikuta K. Serial passage of human immunodeficiency virus type 1 generates misalignment deletions in non-essential accessory genes.. Virus Res 1996 Dec;46(1-2):139-47.
            pubmed: 9029786doi: 10.1016/s0168-1702(96)01396-2google scholar: lookup
          13. Zheng YH, Nakaya T, Sentsui H, Kameoka M, Kishi M, Hagiwara K, Takahashi H, Kono Y, Ikuta K. Insertions, duplications and substitutions in restricted gp90 regions of equine infectious anaemia virus during febrile episodes in an experimentally infected horse.. J Gen Virol 1997 Apr;78 ( Pt 4):807-20.
            pubmed: 9129653doi: 10.1099/0022-1317-78-4-807google scholar: lookup
          14. Kono Y, Kobayashi K. Changes in pathogenicity of equine infectious anemia virus during passages in horse leukocyte cultures.. Natl Inst Anim Health Q (Tokyo) 1970 Fall;10(3):106-12.
            pubmed: 4320651
          15. Kono Y, Kobayashi K, Fukunaga Y. Immunization of horses against equine infectious anemia (EIA) with an attenuated EIA virus.. Natl Inst Anim Health Q (Tokyo) 1970 Fall;10(3):113-22.
            pubmed: 4320652
          16. Kono Y, Kobayashi K, Fukunaga Y. Antigenic drift of equine infectious anemia virus in chronically infected horses.. Arch Gesamte Virusforsch 1973;41(1):1-10.
            pubmed: 4123810doi: 10.1007/BF01249923google scholar: lookup
          17. Nishimura M, Nakajima H. Structural proteins of equine infectious anemia virus and their antigenic activity.. Am J Vet Res 1984 Jan;45(1):5-10.
            pubmed: 6322625
          18. Payne S, Parekh B, Montelaro RC, Issel CJ. Genomic alterations associated with persistent infections by equine infectious anaemia virus, a retrovirus.. J Gen Virol 1984 Aug;65 ( Pt 8):1395-9.
            pubmed: 6086822doi: 10.1099/0022-1317-65-8-1395google scholar: lookup
          19. Montelaro RC, Parekh B, Orrego A, Issel CJ. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus.. J Biol Chem 1984 Aug 25;259(16):10539-44.
            pubmed: 6206055
          20. Salinovich O, Payne SL, Montelaro RC, Hussain KA, Issel CJ, Schnorr KL. Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection.. J Virol 1986 Jan;57(1):71-80.
            pubmed: 3001367doi: 10.1128/JVI.57.1.71-80.1986google scholar: lookup
          21. Payne SL, Salinovich O, Nauman SM, Issel CJ, Montelaro RC. Course and extent of variation of equine infectious anemia virus during parallel persistent infections.. J Virol 1987 Apr;61(4):1266-70.
          22. Hussain KA, Issel CJ, Schnorr KL, Rwambo PM, Montelaro RC. Antigenic analysis of equine infectious anemia virus (EIAV) variants by using monoclonal antibodies: epitopes of glycoprotein gp90 of EIAV stimulate neutralizing antibodies.. J Virol 1987 Oct;61(10):2956-61.
          23. Payne SL, Fang FD, Liu CP, Dhruva BR, Rwambo P, Issel CJ, Montelaro RC. Antigenic variation and lentivirus persistence: variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV.. Virology 1987 Dec;161(2):321-31.
            pubmed: 2825406doi: 10.1016/0042-6822(87)90124-3google scholar: lookup
          24. Roberts JD, Bebenek K, Kunkel TA. The accuracy of reverse transcriptase from HIV-1.. Science 1988 Nov 25;242(4882):1171-3.
            pubmed: 2460925doi: 10.1126/science.2460925google scholar: lookup
          25. Meyerhans A, Cheynier R, Albert J, Seth M, Kwok S, Sninsky J, Morfeldt-Månson L, Asjö B, Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations.. Cell 1989 Sep 8;58(5):901-10.
            pubmed: 2550139doi: 10.1016/0092-8674(89)90942-2google scholar: lookup
          26. Payne SL, Rushlow K, Dhruva BR, Issel CJ, Montelaro RC. Localization of conserved and variable antigenic domains of equine infectious anemia virus envelope glycoproteins using recombinant env-encoded protein fragments produced in Escherichia coli.. Virology 1989 Oct;172(2):609-15.
            pubmed: 2552661doi: 10.1016/0042-6822(89)90203-1google scholar: lookup
          27. Ricchetti M, Buc H. Reverse transcriptases and genomic variability: the accuracy of DNA replication is enzyme specific and sequence dependent.. EMBO J 1990 May;9(5):1583-93.
          28. Goff SP. Retroviral reverse transcriptase: synthesis, structure, and function.. J Acquir Immune Defic Syndr (1988) 1990;3(8):817-31.
            pubmed: 1694894
          29. Pathak VK, Temin HM. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: deletions and deletions with insertions.. Proc Natl Acad Sci U S A 1990 Aug;87(16):6024-8.
            pubmed: 2166940doi: 10.1073/pnas.87.16.6024google scholar: lookup
          30. Alexandersen S, Carpenter S. Characterization of variable regions in the envelope and S3 open reading frame of equine infectious anemia virus.. J Virol 1991 Aug;65(8):4255-62.
          31. Pulsinelli GA, Temin HM. Characterization of large deletions occurring during a single round of retrovirus vector replication: novel deletion mechanism involving errors in strand transfer.. J Virol 1991 Sep;65(9):4786-97.
          32. Ball JM, Rushlow KE, Issel CJ, Montelaro RC. Detailed mapping of the antigenicity of the surface unit glycoprotein of equine infectious anemia virus by using synthetic peptide strategies.. J Virol 1992 Feb;66(2):732-42.
            pubmed: 1370556doi: 10.1128/JVI.66.2.732-742.1992google scholar: lookup
          33. Blumberg BM, Epstein LG, Saito Y, Chen D, Sharer LR, Anand R. Human immunodeficiency virus type 1 nef quasispecies in pathological tissue.. J Virol 1992 Sep;66(9):5256-64.
          34. Embretson J, Zupancic M, Beneke J, Till M, Wolinsky S, Ribas JL, Burke A, Haase AT. Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution.. Proc Natl Acad Sci U S A 1993 Jan 1;90(1):357-61.
            pubmed: 8419941doi: 10.1073/pnas.90.1.357google scholar: lookup
          35. Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.. Nature 1993 Mar 25;362(6418):355-8.
            pubmed: 8455722doi: 10.1038/362355a0google scholar: lookup
          36. Embretson J, Zupancic M, Ribas JL, Burke A, Racz P, Tenner-Racz K, Haase AT. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS.. Nature 1993 Mar 25;362(6418):359-62.
            pubmed: 8096068doi: 10.1038/362359a0google scholar: lookup
          37. Pantaleo G, Demarest JF, Soudeyns H, Graziosi C, Denis F, Adelsberger JW, Borrow P, Saag MS, Shaw GM, Sekaly RP. Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV.. Nature 1994 Aug 11;370(6489):463-7.
            pubmed: 8047166doi: 10.1038/370463a0google scholar: lookup

          Citations

          This article has been cited 20 times.
          1. Malossi CD, Fioratti EG, Cardoso JF, Magro AJ, Kroon EG, Aguiar DM, Borges AMCM, Nogueira MF, Ullmann LS, Araujo JP Jr. High Genomic Variability in Equine Infectious Anemia Virus Obtained from Naturally Infected Horses in Pantanal, Brazil: An Endemic Region Case.. Viruses 2020 Feb 12;12(2).
            doi: 10.3390/v12020207pubmed: 32059508google scholar: lookup
          2. Ahmad I, Li S, Li R, Chai Q, Zhang L, Wang B, Yu C, Zheng YH. The retroviral accessory proteins S2, Nef, and glycoMA use similar mechanisms for antagonizing the host restriction factor SERINC5.. J Biol Chem 2019 Apr 26;294(17):7013-7024.
            doi: 10.1074/jbc.RA119.007662pubmed: 30862674google scholar: lookup
          3. Schwartz EJ, Nanda S, Mealey RH. Antibody escape kinetics of equine infectious anemia virus infection of horses.. J Virol 2015 Jul;89(13):6945-51.
            doi: 10.1128/JVI.00137-15pubmed: 25878104google scholar: lookup
          4. Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity.. Viruses 2013 Dec 2;5(12):2963-76.
            doi: 10.3390/v5122963pubmed: 24316675google scholar: lookup
          5. Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection.. PLoS One 2013;8(6):e66093.
            doi: 10.1371/journal.pone.0066093pubmed: 23785473google scholar: lookup
          6. Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus.. J Virol Methods 2012 Nov;185(2):221-7.
          7. Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Zhou J. Unique evolution characteristics of the envelope protein of EIAV(LN₄₀), a virulent strain of equine infectious anemia virus.. Virus Genes 2011 Apr;42(2):220-8.
            doi: 10.1007/s11262-010-0563-7pubmed: 21369830google scholar: lookup
          8. Cappelli K, Capomaccio S, Cook FR, Felicetti M, Marenzoni ML, Coppola G, Verini-Supplizi A, Coletti M, Passamonti F. Molecular detection, epidemiology, and genetic characterization of novel European field isolates of equine infectious anemia virus.. J Clin Microbiol 2011 Jan;49(1):27-33.
            doi: 10.1128/JCM.01311-10pubmed: 21084503google scholar: lookup
          9. Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.. Vaccine 2010 Nov 29;28(51):8095-104.
            doi: 10.1016/j.vaccine.2010.10.003pubmed: 20955830google scholar: lookup
          10. 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.
            doi: 10.1186/1742-4690-6-95pubmed: 19843328google scholar: lookup
          11. Onafuwa-Nuga A, Telesnitsky A. The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.. Microbiol Mol Biol Rev 2009 Sep;73(3):451-80, Table of Contents.
            doi: 10.1128/MMBR.00012-09pubmed: 19721086google scholar: lookup
          12. Boissin-Quillon A, Piau D, Leroux C. In silico segmentations of lentivirus envelope sequences.. BMC Bioinformatics 2007 Mar 21;8:99.
            doi: 10.1186/1471-2105-8-99pubmed: 17376229google scholar: lookup
          13. Redelings BD, Suchard MA. Incorporating indel information into phylogeny estimation for rapidly emerging pathogens.. BMC Evol Biol 2007 Mar 14;7:40.
            doi: 10.1186/1471-2148-7-40pubmed: 17359539google scholar: lookup
          14. Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.. J Virol 2005 Mar;79(5):2666-77.
          15. 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.
          16. Howe L, Leroux C, Issel CJ, Montelaro RC. Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype.. J Virol 2002 Nov;76(21):10588-97.
          17. Leroux C, Craigo JK, Issel CJ, Montelaro RC. Equine infectious anemia virus genomic evolution in progressor and nonprogressor ponies.. J Virol 2001 May;75(10):4570-83.
          18. Hötzel I, Cheevers WP. Conservation of human immunodeficiency virus type 1 gp120 inner-domain sequences in lentivirus and type A and B retrovirus envelope surface glycoproteins.. J Virol 2001 Feb;75(4):2014-8.
          19. Lonning SM, Zhang W, Leib SR, McGuire TC. Detection and induction of equine infectious anemia virus-specific cytotoxic T-lymphocyte responses by use of recombinant retroviral vectors.. J Virol 1999 Apr;73(4):2762-9.
          20. Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.. J Virol 1997 Dec;71(12):9627-39.