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. 1985 Aug;55(2):417–423. doi: 10.1128/jvi.55.2.417-423.1985

Human T-cell lymphotropic virus type III: immunologic characterization and primary structure analysis of the major internal protein, p24.

J M Casey, Y Kim, P R Andersen, K F Watson, J L Fox, S G Devare
PMCID: PMC254949  PMID: 2410630

Abstract

The major internal structural protein of human T-cell lymphotropic virus type III (HTLV-III), a virus etiologically implicated in acquired immunodeficiency syndrome (AIDS), was purified to homogeneity. This 24,000-molecular-weight protein (p24) was shown to lack immunologic cross-reacting antigenic determinants shared by other known retroviruses, including HTLV-I and HTLV-II, with the exception of equine infectious anemia virus (EIAV). A broadly reactive competition immunoassay was developed in which antiserum to EIAV was used to precipitate 125I-labeled HTLV-III p24. Although the major structural proteins of HTLV-III and EIAV competed in this assay, other type B, C, and D retroviral proteins lacked detectable reactivity. Thus, HTLV-III is more related to EIAV than to any other retroviruses. That the HTLV-III isolate is very distinct from HTLV-I and HTLV-II was further confirmed by the amino acid compositions of the major internal antigens of all three isolates. Moreover, comparison of the amino-terminal amino acid sequence of HTLV-III p24 with analogous sequences for HTLV-I and HTLV-II p24 showed that these proteins do not share significant sequence homology. In an attempt to evaluate immune response in individuals exposed to HTLV-III, sera from AIDS and lymphadenopathy syndrome patients as well as from clinically normal blood donor controls were tested for antibodies to HTLV-III p24. The results showed that sera from 93% of lymphadenopathy syndrome patients and 73% of AIDS patients exhibited high-titered antibodies to HTLV-III p24. In contrast, none of the normal control sera showed detectable reactivity to HTLV-III p24.

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Selected References

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  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. Andersen P. R., Barbacid M., Tronick S. R., Clark H. F., Aaronson S. A. Evolutionary relatedness of viper and primate endogenous retroviruses. Science. 1979 Apr 20;204(4390):318–321. doi: 10.1126/science.219480. [DOI] [PubMed] [Google Scholar]
  3. Arya S. K., Gallo R. C., Hahn B. H., Shaw G. M., Popovic M., Salahuddin S. Z., Wong-Staal F. Homology of genome of AIDS-associated virus with genomes of human T-cell leukemia viruses. Science. 1984 Aug 31;225(4665):927–930. doi: 10.1126/science.6089333. [DOI] [PubMed] [Google Scholar]
  4. August J. T., Bolognesi D. P., Fleissner E., Gilden R. V., Nowinski R. C. A proposed nomenclature for the virion proteins of oncogenic RNA viruses. Virology. 1974 Aug;60(2):595–600. doi: 10.1016/0042-6822(74)90356-0. [DOI] [PubMed] [Google Scholar]
  5. Barbacid M., Long L. K., Aaronson S. A. Major structural proteins of type B, type C, and type D oncoviruses share interspecies antigenic determinants. Proc Natl Acad Sci U S A. 1980 Jan;77(1):72–76. doi: 10.1073/pnas.77.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Black S. D., Coon M. J. Simple, rapid, and highly efficient separation of amino acid phenylthiohydantoins by reversed-phase high-performance liquid chromatography. Anal Biochem. 1982 Apr;121(2):281–285. doi: 10.1016/0003-2697(82)90480-8. [DOI] [PubMed] [Google Scholar]
  9. Charman H. P., Bladen S., Gilden R. V., Coggins L. Equine infectious anemia virus: evidence favoring classification as a retravirus. J Virol. 1976 Sep;19(3):1073–1079. doi: 10.1128/jvi.19.3.1073-1079.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Charman H. P., Kim N., White M., Marquardt H., Gilden R. V., Kawakami T. Natural and experimentally induced antibodies to defined mammalian type-C virus proteins in primates. J Natl Cancer Inst. 1975 Dec;55(6):1419–1424. doi: 10.1093/jnci/55.6.1419. [DOI] [PubMed] [Google Scholar]
  11. Dahlberg J. E., Tronick S. R., Aaronson S. A. Immunological relationships of an endogenous guinea pig retrovirus with prototype mammalian type B and type D retroviruses. J Virol. 1980 Jan;33(1):522–530. doi: 10.1128/jvi.33.1.522-530.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Devare S. G., Kim Y., Fox J. L., Getchell J., Cabradilla C., Kalyanaraman V. S. Human T-cell leukemia virus type II: primary structure analysis of the major internal protein, p24 and the nucleic acid binding protein, p15. Virology. 1985 Apr 15;142(1):206–210. doi: 10.1016/0042-6822(85)90434-9. [DOI] [PubMed] [Google Scholar]
  15. Devare S. G., Stephenson J. R., Sarma P. S., Aaronson S. A., Charder S. Bovine lymphosarcoma: development of a radioimmunologic technique for detection of the etiologic agent. Science. 1976 Dec 24;194(4272):1428–1430. doi: 10.1126/science.188129. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Francis D. P., Feorino P. M., Broderson J. R., McClure H. M., Getchell J. P., McGrath C. R., Swenson B., McDougal J. S., Palmer E. L., Harrison A. K. Infection of chimpanzees with lymphadenopathy-associated virus. Lancet. 1984 Dec 1;2(8414):1276–1277. doi: 10.1016/s0140-6736(84)92824-1. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Kalyanaraman V. S., Sarngadharan M. G., Poiesz B., Ruscetti F. W., Gallo R. C. Immunological properties of a type C retrovirus isolated from cultured human T-lymphoma cells and comparison to other mammalian retroviruses. J Virol. 1981 Jun;38(3):906–915. doi: 10.1128/jvi.38.3.906-915.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kalyanaraman V. S., Sarngadharan M. G., Robert-Guroff M., Miyoshi I., Golde D., Gallo R. C. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982 Nov 5;218(4572):571–573. doi: 10.1126/science.6981847. [DOI] [PubMed] [Google Scholar]
  26. Kawakami T., Buckley P. M., McDowell T. S., DePaoli A. Antibodies to simian C-type virus antigen in sera of gibbons (Hylobates sp.). Nat New Biol. 1973 Nov 28;246(152):105–107. doi: 10.1038/newbio246105a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. 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]
  30. 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]
  31. Markwell M. A. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal Biochem. 1982 Sep 15;125(2):427–432. doi: 10.1016/0003-2697(82)90025-2. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. Oroszlan S., Sarngadharan M. G., Copeland T. D., Kalyanaraman V. S., Gilden R. V., Gallo R. C. Primary structure analysis of the major internal protein p24 of human type C T-cell leukemia virus. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1291–1294. doi: 10.1073/pnas.79.4.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. 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]
  39. Rice N. R., Simek S., Ryder O. A., Coggins L. Detection of proviral DNA in horse cells infected with equine infectious anemia virus. J Virol. 1978 Jun;26(3):577–583. doi: 10.1128/jvi.26.3.577-583.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Safai B., Sarngadharan M. G., Groopman J. E., Arnett K., Popovic M., Sliski A., Schüpbach J., Gallo R. C. Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome. Lancet. 1984 Jun 30;1(8392):1438–1440. doi: 10.1016/s0140-6736(84)91933-0. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Schüpbach J., Popovic M., Gilden R. V., Gonda M. A., Sarngadharan M. G., Gallo R. C. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science. 1984 May 4;224(4648):503–505. doi: 10.1126/science.6200937. [DOI] [PubMed] [Google Scholar]
  44. Scolnick E. M., Parks W. P., Livingston D. M. Radioimmunoassay of mammalian type C viral proteins. I. Species specific reactions of murine and feline viruses. J Immunol. 1972 Sep;109(3):570–577. [PubMed] [Google Scholar]
  45. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. 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]
  48. Stowring L., Haase A. T., Charman H. P. Serological definition of the lentivirus group of retroviruses. J Virol. 1979 Feb;29(2):523–528. doi: 10.1128/jvi.29.2.523-528.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]

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