Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1991 Apr;65(4):1843–1854. doi: 10.1128/jvi.65.4.1843-1854.1991

Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys.

D P Burns 1, R C Desrosiers 1
PMCID: PMC239994  PMID: 2002545

Abstract

Genetic and antigenic variation may be one means by which lentiviruses that cause AIDS avoid elimination by host immune responses. Genetic variation in the envelope gene (env) was studied by comparing the nucleotide sequences of 27 clones obtained from two rhesus monkeys infected with molecularly cloned simian immunodeficiency virus. All 27 clones differed from each other and differed from the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide substitutions were shown to accumulate with time at an average rate of 8.5 per 1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions (81%) resulted in amino acid changes. Variation in SU was not random but occurred predominantly in five discrete regions. Within these variable regions, a remarkable 98% of the nucleotide substitutions changed the amino acid. These results demonstrate that extensive sequence variability accumulates in vivo after infection with molecularly cloned virus and that selection occurs in vivo for changes in distinct variable regions in env.

Full text

PDF
1843

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Buonagurio D. A., Nakada S., Parvin J. D., Krystal M., Palese P., Fitch W. M. Evolution of human influenza A viruses over 50 years: rapid, uniform rate of change in NS gene. Science. 1986 May 23;232(4753):980–982. doi: 10.1126/science.2939560. [DOI] [PubMed] [Google Scholar]
  2. Clements J. E., Pedersen F. S., Narayan O., Haseltine W. A. Genomic changes associated with antigenic variation of visna virus durig persistent infection. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4454–4458. doi: 10.1073/pnas.77.8.4454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coulondre C., Miller J. H., Farabaugh P. J., Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. doi: 10.1038/274775a0. [DOI] [PubMed] [Google Scholar]
  4. DOSKOCIL J., SORM F. Distribution of 5-methylcytosine in pyrimidine sequences of deoxyribonucleic acids. Biochim Biophys Acta. 1962 Jun 11;55:953–959. doi: 10.1016/0006-3002(62)90909-5. [DOI] [PubMed] [Google Scholar]
  5. Desrosiers R. C. Simian immunodeficiency viruses. Annu Rev Microbiol. 1988;42:607–625. doi: 10.1146/annurev.mi.42.100188.003135. [DOI] [PubMed] [Google Scholar]
  6. Dougherty J. P., Temin H. M. Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication. J Virol. 1988 Aug;62(8):2817–2822. doi: 10.1128/jvi.62.8.2817-2822.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis T. M., Wilcox G. E., Robinson W. F. Antigenic variation of caprine arthritis-encephalitis virus during persistent infection of goats. J Gen Virol. 1987 Dec;68(Pt 12):3145–3152. doi: 10.1099/0022-1317-68-12-3145. [DOI] [PubMed] [Google Scholar]
  8. Gardner M. B., Luciw P. A. Simian immunodeficiency viruses and their relationship to the human immunodeficiency viruses. AIDS. 1988;2 (Suppl 1):S3–10. doi: 10.1097/00002030-198800001-00002. [DOI] [PubMed] [Google Scholar]
  9. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  10. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grippo P., Iaccarino M., Parisi E., Scarano E. Methylation of DNA in developing sea urchin embryos. J Mol Biol. 1968 Sep 14;36(2):195–208. doi: 10.1016/0022-2836(68)90375-6. [DOI] [PubMed] [Google Scholar]
  12. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  13. Haigwood N. L., Shuster J. R., Moore G. K., Lee H., Skiles P. V., Higgins K. W., Barr P. J., George-Nascimento C., Steimer K. S. Importance of hypervariable regions of HIV-1 gp120 in the generation of virus neutralizing antibodies. AIDS Res Hum Retroviruses. 1990 Jul;6(7):855–869. doi: 10.1089/aid.1990.6.855. [DOI] [PubMed] [Google Scholar]
  14. Hayashida H., Miyata T. Unusual evolutionary conservation and frequent DNA segment exchange in class I genes of the major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 May;80(9):2671–2675. doi: 10.1073/pnas.80.9.2671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hayashida H., Toh H., Kikuno R., Miyata T. Evolution of influenza virus genes. Mol Biol Evol. 1985 Jul;2(4):289–303. doi: 10.1093/oxfordjournals.molbev.a040352. [DOI] [PubMed] [Google Scholar]
  16. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  17. Ho D. D., Sarngadharan M. G., Hirsch M. S., Schooley R. T., Rota T. R., Kennedy R. C., Chanh T. C., Sato V. L. Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. J Virol. 1987 Jun;61(6):2024–2028. doi: 10.1128/jvi.61.6.2024-2028.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hunt J. C., Desai S. M., Casey J. M., Bolling T. J., Leung T. K., Decker R. H., Devare S. G., Sarin V. Mouse monoclonal antibody 5-21-3 recognizes a contiguous, conformation-dependent epitope and maps to a hydrophilic region in HIV-1 gp41. AIDS Res Hum Retroviruses. 1990 May;6(5):587–598. doi: 10.1089/aid.1990.6.587. [DOI] [PubMed] [Google Scholar]
  19. Kestler H. W., 3rd, Li Y., Naidu Y. M., Butler C. V., Ochs M. F., Jaenel G., King N. W., Daniel M. D., Desrosiers R. C. Comparison of simian immunodeficiency virus isolates. Nature. 1988 Feb 18;331(6157):619–622. doi: 10.1038/331619a0. [DOI] [PubMed] [Google Scholar]
  20. Kestler H., Kodama T., Ringler D., Marthas M., Pedersen N., Lackner A., Regier D., Sehgal P., Daniel M., King N. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. doi: 10.1126/science.2160735. [DOI] [PubMed] [Google Scholar]
  21. Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
  22. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  23. Leis J., Baltimore D., Bishop J. M., Coffin J., Fleissner E., Goff S. P., Oroszlan S., Robinson H., Skalka A. M., Temin H. M. Standardized and simplified nomenclature for proteins common to all retroviruses. J Virol. 1988 May;62(5):1808–1809. doi: 10.1128/jvi.62.5.1808-1809.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Li W. H., Gojobori T. Rapid evolution of goat and sheep globin genes following gene duplication. Mol Biol Evol. 1983 Dec;1(1):94–108. doi: 10.1093/oxfordjournals.molbev.a040306. [DOI] [PubMed] [Google Scholar]
  25. Li W. H., Wu C. I., Luo C. C. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol. 1985 Mar;2(2):150–174. doi: 10.1093/oxfordjournals.molbev.a040343. [DOI] [PubMed] [Google Scholar]
  26. Li W. H., Wu C. I., Luo C. C. Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications. J Mol Evol. 1984;21(1):58–71. doi: 10.1007/BF02100628. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Naidu Y. M., Kestler H. W., 3rd, Li Y., Butler C. V., Silva D. P., Schmidt D. K., Troup C. D., Sehgal P. K., Sonigo P., Daniel M. D. Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol. 1988 Dec;62(12):4691–4696. doi: 10.1128/jvi.62.12.4691-4696.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nara P. L., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Gallo R. C., Fischinger P. J., Goudsmit J. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol. 1990 Aug;64(8):3779–3791. doi: 10.1128/jvi.64.8.3779-3791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Preston B. D., Poiesz B. J., Loeb L. A. Fidelity of HIV-1 reverse transcriptase. Science. 1988 Nov 25;242(4882):1168–1171. doi: 10.1126/science.2460924. [DOI] [PubMed] [Google Scholar]
  32. Regier D. A., Desrosiers R. C. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. doi: 10.1089/aid.1990.6.1221. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Roberts J. D., Preston B. D., Johnston L. A., Soni A., Loeb L. A., Kunkel T. A. Fidelity of two retroviral reverse transcriptases during DNA-dependent DNA synthesis in vitro. Mol Cell Biol. 1989 Feb;9(2):469–476. doi: 10.1128/mcb.9.2.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Scott J. V., Stowring L., Haase A. T., Narayan O., Vigne R. Antigenic variation in visna virus. Cell. 1979 Oct;18(2):321–327. doi: 10.1016/0092-8674(79)90051-5. [DOI] [PubMed] [Google Scholar]
  40. Simmonds P., Balfe P., Peutherer J. F., Ludlam C. A., Bishop J. O., Brown A. J. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990 Feb;64(2):864–872. doi: 10.1128/jvi.64.2.864-872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]
  42. Takahashi H., Cohen J., Hosmalin A., Cease K. B., Houghten R., Cornette J. L., DeLisi C., Moss B., Germain R. N., Berzofsky J. A. An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1988 May;85(9):3105–3109. doi: 10.1073/pnas.85.9.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989 May;63(5):2118–2125. doi: 10.1128/jvi.63.5.2118-2125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tindall K. R., Kunkel T. A. Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase. Biochemistry. 1988 Aug 9;27(16):6008–6013. doi: 10.1021/bi00416a027. [DOI] [PubMed] [Google Scholar]
  45. Veronese F. D., Joseph B., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Identification of simian immunodeficiency virus SIVMAC env gene products. J Virol. 1989 Mar;63(3):1416–1419. doi: 10.1128/jvi.63.3.1416-1419.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  47. Weber J., Grosse F. Fidelity of human immunodeficiency virus type I reverse transcriptase in copying natural DNA. Nucleic Acids Res. 1989 Feb 25;17(4):1379–1393. doi: 10.1093/nar/17.4.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wilson C., Reitz M. S., Jr, Aldrich K., Klasse P. J., Blomberg J., Gallo R. C., Robert-Guroff M. The site of an immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 does not constitute the neutralization epitope. J Virol. 1990 Jul;64(7):3240–3248. doi: 10.1128/jvi.64.7.3240-3248.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES