Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Aug;83(15):5718–5722. doi: 10.1073/pnas.83.15.5718

Genomic diversity of the acquired immunodeficiency syndrome retroviruses is reflected in alteration of its translational products.

S G Devare, A Srinivasan, C A Bohan, T J Spira, J W Curran, V S Kalyanaraman
PMCID: PMC386360  PMID: 3016717

Abstract

We have isolated retroviruses from six acquired immunodeficiency syndrome (AIDS) and three lymphadenopathy syndrome (LAS) patients by cocultivation of patients' lymphocytes with phytohemagglutinin-stimulated normal T cells. In an effort to address the extent to which these viruses have identical genetic information or there is divergence in their genomic sequences, we have compared the nine retrovirus isolates by the following criteria: (i) antigenic cross-reactivity by highly specific and sensitive competition radioimmunoassay for the major internal antigen; (ii) restriction site mapping analysis; and (iii) immunoblot analysis and metabolic labeling of viral structural proteins and their analysis by polyacrylamide gel electrophoresis. The data indicate that individual retroviruses have significant restriction site polymorphism in their genome even though they were isolated from patients residing at one geographic location. Furthermore, this polymorphism is reflected in the variation of the apparent size of the gag and env gene-encoded structural proteins. The heterogeneity in AIDS retrovirus-encoded proteins may be due to either substitutions in the primary amino acid sequence of the protein or deletions or additions in the coding regions of proteins. The alterations in viral structural proteins among various AIDS retroviruses could have important implications in antigenic properties and/or pathogenicity in development of the disease, its detection, and ultimately its eradication.

Full text

PDF
5718

Images in this article

5719Image
on p.5719
5720Image
on p.5720
5720Image
on p.5720

Selected References

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

  1. Alizon M., Sonigo P., Barré-Sinoussi F., Chermann J. C., Tiollais P., Montagnier L., Wain-Hobson S. Molecular cloning of lymphadenopathy-associated virus. Nature. 1984 Dec 20;312(5996):757–760. doi: 10.1038/312757a0. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M., Stephenson J. R., Aaronson S. A. Evolutionary relationships between gag gene-coded proteins of murine and primate endogenous type C RNA viruses. Cell. 1977 Apr;10(4):641–648. doi: 10.1016/0092-8674(77)90097-6. [DOI] [PubMed] [Google Scholar]
  3. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  4. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  5. Casey J. M., Kim Y., Andersen P. R., Watson K. F., Fox J. L., Devare S. G. Human T-cell lymphotropic virus type III: immunologic characterization and primary structure analysis of the major internal protein, p24. J Virol. 1985 Aug;55(2):417–423. doi: 10.1128/jvi.55.2.417-423.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. DeLarco J., Todaro G. J. Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71. Cell. 1976 Jul;8(3):365–371. doi: 10.1016/0092-8674(76)90148-3. [DOI] [PubMed] [Google Scholar]
  8. Devare S. G., Arthur L. O., Fine D. L., Stephenson J. R. Primate retroviruses: immunological cross-reactivity between major structural proteins of new and old world primate virus isolates. J Virol. 1978 Mar;25(3):797–805. doi: 10.1128/jvi.25.3.797-805.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feorino P. M., Kalyanaraman V. S., Haverkos H. W., Cabradilla C. D., Warfield D. T., Jaffe H. W., Harrison A. K., Gottlieb M. S., Goldfinger D., Chermann J. C. Lymphadenopathy associated virus infection of a blood donor--recipient pair with acquired immunodeficiency syndrome. Science. 1984 Jul 6;225(4657):69–72. doi: 10.1126/science.6328663. [DOI] [PubMed] [Google Scholar]
  10. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  11. Gonda M. A., Wong-Staal F., Gallo R. C., Clements J. E., Narayan O., Gilden R. V. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science. 1985 Jan 11;227(4683):173–177. doi: 10.1126/science.2981428. [DOI] [PubMed] [Google Scholar]
  12. Hahn B. H., Gonda M. A., Shaw G. M., Popovic M., Hoxie J. A., Gallo R. C., Wong-Staal F. Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813–4817. doi: 10.1073/pnas.82.14.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hahn B. H., Shaw G. M., Arya S. K., Popovic M., Gallo R. C., Wong-Staal F. Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature. 1984 Nov 8;312(5990):166–169. doi: 10.1038/312166a0. [DOI] [PubMed] [Google Scholar]
  14. Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
  15. 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]
  16. Ikeda H., Pincus T., Yoshiki T., Strand M., August J. T., Boyse E. A., Mellors R. C. Biological expression of antigenic determinants of murine leukemia virus proteins gp69-71 and p30. J Virol. 1974 Nov;14(5):1274–1280. doi: 10.1128/jvi.14.5.1274-1280.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ishizaki R., Vogt P. K. Immunological relationships among envelope antigens of avian tumor viruses. Virology. 1966 Nov;30(3):375–387. doi: 10.1016/0042-6822(66)90116-4. [DOI] [PubMed] [Google Scholar]
  18. Jaffe H. W., Sarngadharan M. G., DeVico A. L., Bruch L., Getchell J. P., Kalyanaraman V. S., Haverkos H. W., Stoneburner R. L., Gallo R. C., Curran J. W. Infection with HTLV-III/LAV and transfusion-associated acquired immunodeficiency syndrome. Serologic evidence of an association. JAMA. 1985 Aug 9;254(6):770–773. [PubMed] [Google Scholar]
  19. Kalyanaraman V. S., Cabradilla C. D., Getchell J. P., Narayanan R., Braff E. H., Chermann J. C., Barré-Sinoussi F., Montagnier L., Spira T. J., Kaplan J. Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS. Science. 1984 Jul 20;225(4659):321–323. doi: 10.1126/science.6330889. [DOI] [PubMed] [Google Scholar]
  20. Kitchen L. W., Barin F., Sullivan J. L., McLane M. F., Brettler D. B., Levine P. H., Essex M. Aetiology of AIDS--antibodies to human T-cell leukaemia virus (type III) in haemophiliacs. Nature. 1984 Nov 22;312(5992):367–369. doi: 10.1038/312367a0. [DOI] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
  23. Luciw P. A., Potter S. J., Steimer K., Dina D., Levy J. A. Molecular cloning of AIDS-associated retrovirus. Nature. 1984 Dec 20;312(5996):760–763. doi: 10.1038/312760a0. [DOI] [PubMed] [Google Scholar]
  24. Moldow C. F., Kauffman R. S., Devare S. G., Stephenson J. R. Type-C and type-D primate retrovirus envelope glycoproteins bind common cellular receptor sites. Virology. 1979 Oct 30;98(2):373–384. doi: 10.1016/0042-6822(79)90560-9. [DOI] [PubMed] [Google Scholar]
  25. Montagnier L., Gruest J., Chamaret S., Dauguet C., Axler C., Guétard D., Nugeyre M. T., Barré-Sinoussi F., Chermann J. C., Brunet J. B. Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines. Science. 1984 Jul 6;225(4657):63–66. doi: 10.1126/science.6328661. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Oroszlan S., Copeland T. D., Henderson L. E., Stephenson J. R., Gilden R. V. Amino-terminal sequence of bovine leukemia virus major internal protein: homology with mammalian type C virus p30 structural proteins. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2996–3000. doi: 10.1073/pnas.76.6.2996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Oroszlan S., Henderson L. E., Stephenson J. R., Copeland T. D., Long C. W., Ihle J. N., Gilden R. V. Amino- and carboxyl-terminal amino acid sequences of proteins coded by gag gene of murine leukemia virus. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1404–1408. doi: 10.1073/pnas.75.3.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Parks W. P., Scolnick E. M. Radioimmunoassay of mammalian type-C viral proteins: interspecies antigenic reactivities of the major internal polypeptide. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1766–1770. doi: 10.1073/pnas.69.7.1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  32. Rabson A. B., Martin M. A. Molecular organization of the AIDS retrovirus. Cell. 1985 Mar;40(3):477–480. doi: 10.1016/0092-8674(85)90189-8. [DOI] [PubMed] [Google Scholar]
  33. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  34. Sanchez-Pescador R., Power M. D., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., Renard A., Randolph A., Levy J. A. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484–492. doi: 10.1126/science.2578227. [DOI] [PubMed] [Google Scholar]
  35. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  36. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  37. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  38. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  39. Steeves R. A., Strand M., August J. T. Structural proteins of mammalian oncogenic RNA viruses: murine leukemia virus neutralization by antisera prepared against purified envelope glycoprotein. J Virol. 1974 Jul;14(1):187–189. doi: 10.1128/jvi.14.1.187-189.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stephenson J. R., Reynolds R. K., Devare S. G., Reynolds F. H. Biochemical and immunological properties of gag genecoded structural proteins of endogenous tyep C RNA tumor viruses of diverse mammalian species. J Biol Chem. 1977 Nov 10;252(21):7818–7825. [PubMed] [Google Scholar]
  41. 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]
  42. Wong-Staal F., Shaw G. M., Hahn B. H., Salahuddin S. Z., Popovic M., Markham P., Redfield R., Gallo R. C. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. doi: 10.1126/science.2992084. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES