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. 1997 Jul;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.

Y H Zheng 1, H Sentsui 1, T Nakaya 1, Y Kono 1, K Ikuta 1
PMCID: PMC191736  PMID: 9188568

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.

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Selected References

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  1. 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):4255–4262. doi: 10.1128/jvi.65.8.4255-4262.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball J. M., Rushlow K. E., Issel C. J., Montelaro R. C. 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):732–742. doi: 10.1128/jvi.66.2.732-742.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blumberg B. M., Epstein L. G., Saito Y., Chen D., Sharer L. R., Anand R. Human immunodeficiency virus type 1 nef quasispecies in pathological tissue. J Virol. 1992 Sep;66(9):5256–5264. doi: 10.1128/jvi.66.9.5256-5264.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cao Y., Ho D. D., Todd J., Kokka R., Urdea M., Lifson J. D., Piatak M., Jr, Chen S., Hahn B. H., Saag M. S. Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AIDS Res Hum Retroviruses. 1995 Mar;11(3):353–361. doi: 10.1089/aid.1995.11.353. [DOI] [PubMed] [Google Scholar]
  5. Embretson J., Zupancic M., Beneke J., Till M., Wolinsky S., Ribas J. L., Burke A., Haase A. T. 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):357–361. doi: 10.1073/pnas.90.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  7. Goff S. P. Retroviral reverse transcriptase: synthesis, structure, and function. J Acquir Immune Defic Syndr. 1990;3(8):817–831. [PubMed] [Google Scholar]
  8. Hussain K. A., Issel C. J., Schnorr K. L., Rwambo P. M., Montelaro R. C. 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):2956–2961. doi: 10.1128/jvi.61.10.2956-2961.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kishi M., Zheng Y. H., Bahmani M. K., Tokunaga K., Takahashi H., Kakinuma M., Lai P. K., Nonoyama M., Luftig R. B., 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):7507–7518. doi: 10.1128/jvi.69.12.7507-7518.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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):106–112. [PubMed] [Google Scholar]
  11. 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. doi: 10.1007/BF01249923. [DOI] [PubMed] [Google Scholar]
  12. 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):113–122. [PubMed] [Google Scholar]
  13. Koup R. A., Safrit J. T., Cao Y., Andrews C. A., McLeod G., Borkowsky W., Farthing C., Ho D. D. 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):4650–4655. doi: 10.1128/jvi.68.7.4650-4655.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lichtenstein D. L., Issel C. J., Montelaro R. C. 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):3346–3354. doi: 10.1128/jvi.70.6.3346-3354.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  16. Michael N. L., Mo T., Merzouki A., O'Shaughnessy M., Oster C., Burke D. S., Redfield R. R., Birx D. L., Cassol S. A. 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):1868–1877. doi: 10.1128/jvi.69.3.1868-1877.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Montelaro R. C., Parekh B., Orrego A., Issel C. J. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus. J Biol Chem. 1984 Aug 25;259(16):10539–10544. [PubMed] [Google Scholar]
  18. Nakaya T., Fujinaga K., Doi H., Suzuki S., Takahashi H., Nishino Y., Kishi M., Azuma I., Luftig R. B., 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):139–147. doi: 10.1016/s0168-1702(96)01396-2. [DOI] [PubMed] [Google Scholar]
  19. 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] [Google Scholar]
  20. Palaniappan C., Wisniewski M., Wu W., Fay P. J., Bambara R. A. Misincorporation by HIV-1 reverse transcriptase promotes recombination via strand transfer synthesis. J Biol Chem. 1996 Sep 13;271(37):22331–22338. doi: 10.1074/jbc.271.37.22331. [DOI] [PubMed] [Google Scholar]
  21. Pantaleo G., Demarest J. F., Soudeyns H., Graziosi C., Denis F., Adelsberger J. W., Borrow P., Saag M. S., Shaw G. M., Sekaly R. P. 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):463–467. doi: 10.1038/370463a0. [DOI] [PubMed] [Google Scholar]
  22. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  23. Pathak V. K., Temin H. M. 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):6024–6028. doi: 10.1073/pnas.87.16.6024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Payne S. L., Fang F. D., Liu C. P., Dhruva B. R., Rwambo P., Issel C. J., Montelaro R. C. 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):321–331. doi: 10.1016/0042-6822(87)90124-3. [DOI] [PubMed] [Google Scholar]
  25. Payne S. L., Rushlow K., Dhruva B. R., Issel C. J., Montelaro R. C. 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):609–615. doi: 10.1016/0042-6822(89)90203-1. [DOI] [PubMed] [Google Scholar]
  26. Payne S. L., Salinovich O., Nauman S. M., Issel C. J., Montelaro R. C. Course and extent of variation of equine infectious anemia virus during parallel persistent infections. J Virol. 1987 Apr;61(4):1266–1270. doi: 10.1128/jvi.61.4.1266-1270.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Payne S., Parekh B., Montelaro R. C., Issel C. J. Genomic alterations associated with persistent infections by equine infectious anaemia virus, a retrovirus. J Gen Virol. 1984 Aug;65(Pt 8):1395–1399. doi: 10.1099/0022-1317-65-8-1395. [DOI] [PubMed] [Google Scholar]
  28. Perelson A. S., Neumann A. U., Markowitz M., Leonard J. M., Ho D. D. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996 Mar 15;271(5255):1582–1586. doi: 10.1126/science.271.5255.1582. [DOI] [PubMed] [Google Scholar]
  29. Pulsinelli G. A., Temin H. M. 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):4786–4797. doi: 10.1128/jvi.65.9.4786-4797.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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):1583–1593. doi: 10.1002/j.1460-2075.1990.tb08278.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roberts J. D., Bebenek K., Kunkel T. A. The accuracy of reverse transcriptase from HIV-1. Science. 1988 Nov 25;242(4882):1171–1173. doi: 10.1126/science.2460925. [DOI] [PubMed] [Google Scholar]
  32. Salinovich O., Payne S. L., Montelaro R. C., Hussain K. A., Issel C. J., Schnorr K. L. Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection. J Virol. 1986 Jan;57(1):71–80. doi: 10.1128/jvi.57.1.71-80.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sellon D. C., Fuller F. J., McGuire T. C. The immunopathogenesis of equine infectious anemia virus. Virus Res. 1994 May;32(2):111–138. doi: 10.1016/0168-1702(94)90038-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tao B., Fultz P. N. Molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, SIVsmmPBj14. J Virol. 1995 Apr;69(4):2031–2037. doi: 10.1128/jvi.69.4.2031-2037.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Temin H. M. 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):6900–6903. doi: 10.1073/pnas.90.15.6900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  37. Zheng Y. H., 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):807–820. doi: 10.1099/0022-1317-78-4-807. [DOI] [PubMed] [Google Scholar]

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