Using Synthetic Peptide Reagents to Distinguish Infections Caused by Different HIV Strains

  • J. W. GnannJr.
  • M. B. A. Oldstone
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 160)


As the nucleic acid sequences of additional isolates of human immunodeficiency virus (HIV) have been determined, the remarkable heterogeneity within this group of viruses has become apparent. HIV has been subclassified into HIV type 1, the retrovirus first shown to cause the acquired immunodeficiency syndrome (AIDS), and HIV type 2, a more recently discovered retrovirus prevalent in West Africa. HIV-1 and HIV-2 have identical amino acids at about 59% of positions in the relatively conserved core proteins and at about 42% of positions in the envelope proteins (Guyader et al. 1987). There is partial antigenic cross-reactivity between the core proteins of the two viruses, but cross-reactivity between envelope proteins has not been described (Clavel et al. 1986, 1987; Brun-Vezinet et al. 1987). Consequently, an enzyme-linked immunosorbent assay (ELISA) containing HIV-1 whole-virus lysate as an antigen detects some HIV-2-positive sera, but is an inconsistent and unreliable test for HIV-2 diagnosis.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Synthetic Peptide Antigenic Determinant Transmembrane Glycoprotein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alizon M, Wain-Hobson S, Montagnier L, Sonigo P (1986) Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell 46: 63 - 74PubMedCrossRefGoogle Scholar
  2. Benn S, Rultedge R, Folks T, Gold J, Baker L, McCormick J, Feorino P, Piot P, Quinn T, Martin MA (1985) Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science 230: 949 - 951PubMedCrossRefGoogle Scholar
  3. Brun-Vezinet F, Rouzioux C, Montagnier L, Chamaret S, Gruest J, Barre-Sinoussi F, Gerolid D, Chermann JC, McCormick J, Mitchell S, Piot P, Taelman H, Mirlangu KB, Wobin O, Mbendi N, Mazebo P, Kalambayi K, Bridts C, Desmyter J, Feinsod FM, Quinn TC (1984) Prevalence of antibodies to lymphadenopathy associated retrovirus in African patients with AIDS. Science 226: 453 - 456PubMedCrossRefGoogle Scholar
  4. Brun-Vezinet F, Rey MA, Katlama C, Girard PM, Roulot D, Yeni P, Lenoble L, Clavel F, Alizon M, Gadelle S, Madjar JJ, Harzic M (1987) Lymphadenopathy associated virus type 2 in AIDS and AIDS-rated complex: clinical and virological features in four patients. Lancet is 128-132Google Scholar
  5. Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA (1987) Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci USA 84: 3526 - 3530PubMedCrossRefGoogle Scholar
  6. Cheng-Mayer C, Seto D, Tateno M, Levy JA (1988) Biological features of HIV-1 that correlate with virulence in the host. Science 240: 80 - 82PubMedCrossRefGoogle Scholar
  7. Chou PY, Fasman GD (1978) Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol 47: 45 - 148PubMedGoogle Scholar
  8. Clavel F, Guetard D, Brun-Vezinet F, Chamaret S, Rey MA, Santos-Ferreira MO, Laurent AG, Dauguet C, Katlama C, Rouzioux C, Klatzman D, Champalimaud JL, Montagnier L (1986) Isolation of a new human retrovirus from West African patients with AIDS. Science 233: 343 - 346PubMedCrossRefGoogle Scholar
  9. Clavel F, Mansinho K, Chamaret S, Guetard D, Favier V, Nina J, Santos-Ferreira MO, Champalimaund JL, Montagnier L (1987) Human immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med 316: 1180 - 1185PubMedCrossRefGoogle Scholar
  10. Coffin JM (1986) Genetic variation in AIDS viruses. Cell 46: 1 - 4PubMedCrossRefGoogle Scholar
  11. Dahl K, Martin K, Miller G (1987) Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus. J Virol 61: 1602 - 1608PubMedGoogle Scholar
  12. Desai SM, Kalyanaraman VS, Casey JM, Srinivasan A, Andersen PR, Devare SG (1986) Molecular cloning and primary nucleotide sequence analysis of a distinct human immunodeficiency virus isolate reveal significant divergence in its genomic sequences. Proc Natl Acad Sci (USA) 83: 8380-8384PubMedCrossRefGoogle Scholar
  13. Evans LA, McHugh TM, Stites DP, Levy JA (1987) Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol 138: 3415 - 3418PubMedGoogle Scholar
  14. Gnann JW, Schwimmbeck PL, Nelson JA, Truax AB, Oldstone MBA (1987a) Diagnosis of AIDS using a 12 amino acid peptide representing an immunodominat epitope of human immunodeficiency virus. J Infect Dis 156: 261 - 267PubMedCrossRefGoogle Scholar
  15. Gnann JW, Nelson JA, Oldstone MBA (1987b) Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol 61: 2639 - 2641PubMedGoogle Scholar
  16. Gnann JW, McCormick JB, Mitchell S, Nelson JA, Oldstone MBA (1978c) Synthetic peptide immunoassay distinguishes HIV type 1 and type 2 infections. Science 237: 1346 - 1349CrossRefGoogle Scholar
  17. Gnann JW, Smith LL, Oldstone MBA (1989) Custom-designed synthetic peptide immunoassays for distinguishing HIV type 1 and type 2 infections. In: Langone JL (ed) Methods in enzymology: immunochemical techniques—anti-idiotypic antibodies and molecular mimicry, Academic Press, Orlando, FL, pp. 693 - 714.Google Scholar
  18. Gurgo C, Guo H-G, Franchini G, Aldovini A, Collalti E, Farrell K, Wong-Staal F, Gallo RC, Reitz MS (1988) Envelope sequences of two new United States HIV-1 isolates. Virology 164: 531 - 536PubMedCrossRefGoogle Scholar
  19. Guyader M, Emerman M, Sonigo P, Clavel F, Montagnier L, Alizon M (1987) Genome organization and transactivation of the human immunodeficiency virus type 2. Nature 326: 622 - 669CrossRefGoogle Scholar
  20. Hahn BH, Gonda MA, Shaw GM, Popovic M, Hoxie J, Gallo RC, Wong-Staal F (1985) Genomic diversity of the AIDS virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci USA 82: 4813 - 4817PubMedCrossRefGoogle Scholar
  21. Hopp TP, Woods KR (1981) Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA 78: 3824 - 3828PubMedCrossRefGoogle Scholar
  22. Kennedy RC, Henkel RD, Pauletti D, Allan JS, Lee TH, Essex M, Dreesman GR (1986) Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein. Science 231: 1556 - 1559PubMedCrossRefGoogle Scholar
  23. Lerner RA (1984) Antibodies of predetermined specificity in biology and medicine. Adv Immunol 36: 1 - 44PubMedCrossRefGoogle Scholar
  24. Modrow S, Hahn BH, Shaw GM, Gallo RC, Wong-Staal F, Wolf H (1987) Computer assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol 61: 570 - 578PubMedGoogle Scholar
  25. Norrby E, Biberfeld G, Chiodi F, von Gegerfeldt A, Naucler A, Parks E, Lerner R (1987) Discrimination between antibodies to HIV and to related retroviruses using site-directed serology. Nature 329: 248 - 250PubMedCrossRefGoogle Scholar
  26. Palker TJ, Matthews TJ, Clark ME, Cianciolo GJ, Randall RR, Langlois AJ, White GC, Safai B, Snyderman R, Bolognesi DP, Haynes BF (1987) A conserved region at the COOH terminus of human immunodeficiency virus gpI20 envelope protein contains an immunodominant epitope. Proc Natl Acad Sci USA 84: 2479 - 2483PubMedCrossRefGoogle Scholar
  27. Palker TJ, Clark ME, Langlois Ai, Matthews TJ, Weinhold KJ, Randall RR, Bolognesi DP, Haynes BF (1988) Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci USA 85: 1932 - 1936PubMedCrossRefGoogle Scholar
  28. Pauletti D, Simmonds R, Dreesman GR, Kennedy RC (1985) Application of a modified computer algorithm in determining potential antigenic determinants associated with the AIDS virus glycoprotein. Anal Biochem 151: 540 - 546PubMedCrossRefGoogle Scholar
  29. Prince AM, Pascual D, Kosolapov LB, Kurokawa D, Baker L, Rubinstein P (1987) Prevalence, clinical significance, and strain specificity of neutralizing antibody to the human immunodeficiency virus. J Infect Dis 156: 268 - 272PubMedCrossRefGoogle Scholar
  30. Ratner L, Haseltine W, Patarca R, Livak KJ, Starich B, Josephs SF, Doran FR, Rafalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo RC, Wong-Staal F (1985) Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313: 277-284Google Scholar
  31. Sanchez-Pescador R, Power MD, Barr PJ, Steimer KS, Stempien MM, Brown-Shimer SL, Gee WW, Renard A, Randolph A, Levy JA, Dina D, Luciw PA (1985) Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 227: 484 - 492PubMedCrossRefGoogle Scholar
  32. Schrier RD, Gnann JW, Langlois Ai, Shriver K, Nelson JA, Oldstone MBA (1988) B and T lymphocyte responses to an immunodominant epitope of human immunodeficiency virus. J Virol 62: 2531 - 2536PubMedGoogle Scholar
  33. Smith RS, Naso RB, Rosen J, Whalley Am Horn YL, Hoey K, Kennedy CJ, McCutchan JA, Spector SA, Richman DD (1987) Antibody to a synthetic oligopeptide in subjects at risk for human immunodeficiency virus infection. J Clin Microbiol 25: 1498 - 1504PubMedGoogle Scholar
  34. Schochetman G, Curran J, Kalyanaraman VS, Luciw PA, Sanchez-Pescador R (1987) Molecular characterization of human immunodeficiency virus from Zaire: nucleotide sequence analysis identifies conserved and variable domains in the envelope gene. Gene 52: 71 - 82PubMedCrossRefGoogle Scholar
  35. Sternberg MJ, Barton GJ, Zvelebil MJ, Cookson J, Coates ARM (1987) Prediction of antigenic determinants and secondary structures of the major AIDS virus proteins. FEBS Lett 218: 231-237Google Scholar
  36. Starcich BR, Hahn BH, Shaw GM, McNeely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, Wong-Staal F (1986) Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell 45: 637 - 748PubMedCrossRefGoogle Scholar
  37. Sutcliffe JG, Shinnick TM, Green N, Lerner RA (1983) Antibodies that react with predetermined sites on proteins. Science 219: 660 - 666PubMedCrossRefGoogle Scholar
  38. Tainer JA, Getzoff ED, Alexander H, Houghten RA, Olson AJ, Lerner RA, Hendrickson WA (1984) The reactivity of antipeptide antibodies is a function of the atomic mobility of sites in a protein. Nature 312: 127 - 134PubMedCrossRefGoogle Scholar
  39. Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M (1985) Nucleotide sequence of the AIDS virus, LAV. Cell 40: 9-17Google Scholar
  40. Walter G, Scheidtmann KH, Carbone A, Laudana AP, Doolittle RF (1980) Antibodies specific for the carboxy-and amino-terminal regions of simian virus 40 large antigen. Proc Natl Acad Sci USA 77: 5197 - 5200PubMedCrossRefGoogle Scholar
  41. Wang JJG, Steel S, Wisniewolski R, Wang CY (1986) Detection of antibodies to human Tlymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein. Proc Natl Acad Sci USA 83: 6159 - 6163PubMedCrossRefGoogle Scholar
  42. Westhof E, Altschuh D, Moras D, Bloomer AC, Mondragon A, Klug A, Van Regenmortel MHV (1984) Correlation between segmental mobility and the location of antigenic determinants in proteins. Nature 311: 123 - 126PubMedCrossRefGoogle Scholar
  43. Willey RL, Rutledge RA, Dias S, Folks T, Theodore T, Buckler CE, Martin MA (1986) Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc Natl Acad Sci (USA) 83: 5038 - 5042CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1990

Authors and Affiliations

  • J. W. GnannJr.
    • 1
  • M. B. A. Oldstone
    • 1
  1. 1.Department of ImmunologyScripps Clinic and Research FoundationLa JollaUSA

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