Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Is a Positive Western Blot Proof of HIV Infection?

Abstract

It is currently accepted that a positive Western blot (WB) HIV antibody test is synonymous with HIV infection and the attendant risk of developing AIDS. In this communication we present a critical evaluation of the presently available data on HTV isolation and antibody testing. This evidence indicates that: (1) the antibody tests are not standardized; (2) the antibody tests are not reproducible; (3) the WB proteins (bands) which are considered to be encoded by the HTV genome and to be specific to HIV may not be encoded by the HIV genome and may in fact represent normal cellular proteins; (4) even if the proteins are specific to HIV, because no gold standard has been used to determine specificity, a positive WB may represent nothing more than cross-reactivity with non-HIV antibodies present in AIDS patients and those at risk. We conclude that the use of antibody tests as a diagnostic and epidemiological tool for HIV infection needs to be reappraised.

References

  1. 1

    Ratner, L., Haseltine, W., Patarca, R.P. et al. 1985. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313: 277–284.

    CAS  Google Scholar 

  2. 2

    Hausmann, E.H.S., Gelderblom, H.R., Clapham, P.R. et al. 1987. Detection of HIV envelope specific antibodies by immunoelectron microscopy and correlation with antibody liter and virus neutralizing activity. J. Virol. Meth. 16: 125–137.

    CAS  Google Scholar 

  3. 3

    Pinter, A., Honnen, W.J., Tilley, S.A. et al. 1989. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J. Virol. 63: 2674–2679.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Barré-Sinoussi, F., Chermann, J.C., Rey, F. et al. 1983. Isolation of a T-lymphotrophic retrovirus from a patient at risk for Acquired Immune Deficiency Syndrome (AIDS). Science 220: 868–871.

    Google Scholar 

  5. 5

    Schüpbach, J., Popovic, M., Gilden, R.V. et al. 1984. Serological analysis of a subgroup of human T-lymphotrophic retroviruses (HTLV-III) associated with AIDS. Science 224: 503–505.

    Google Scholar 

  6. 6

    Damsky, C.H., Sheffield, J.B., Tuszynski, G.P. et al. 1977. Is there a role for actin in virus budding? J. Cell. Biol. 75: 593–605.

    CAS  PubMed  Google Scholar 

  7. 7

    Stanislawsky, L., Mongiat, F., Neto, V.M. et al. 1984. Presence of actin in oncornaviruses. Biochem. Biophys. Res. Com. 118: 580–586.

    CAS  PubMed  Google Scholar 

  8. 8

    Papadopulos-Eleopulos, E., Turner, V.F. and Papadimitriou, J.M. 1992. Oxidative stress, HIV and AIDS. Res. Immunol. 143: 145–148.

    CAS  PubMed  Google Scholar 

  9. 9

    Hinshaw, D.B., Burger, J.M., Beals, T.F. et al. 1991. Actin polymerization in cellular oxidant injury. Arch. Biochem. Biophys. 228: 311–316.

    Google Scholar 

  10. 10

    Bach, M.A., Lewis, D.E., McClure, J.E. et al. 1986. Monoclonal anti-actin antibody recognizes a surface molecule on normal and transformed human B lymphocytes: Expression varies with phase of cell cycle. Cell. Immunol. 98: 364–374.

    CAS  PubMed  Google Scholar 

  11. 11

    Stricker, R.B., Abrams, D.I., Corash, L. et al. 1985. Target platelet antigen in homosexual men with immune thrombocytopenia. NEJM 313: 1375–1380.

    CAS  PubMed  Google Scholar 

  12. 12

    Henderson, L.E., Sowder, R., Copeland, T.D. et al. 1987. Direct identification of class II histocompatibility DR proteins in preparations of human T-cell lymphotropic virus type III. J. Virol. 61: 629–632.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Wong-Staal, F. and Gallo, R.C. 1985. Human T-lymphotropic retroviruses. Nature 317: 395–403.

    CAS  PubMed  Google Scholar 

  14. 14

    Genesca, J., Jett, B.W., Epstein, J.S. et al. 1989. What do Western blot indeterminate patterns for Human Immunodeficiency Virus mean in EIA-negative blood donors? Lancet II: 1023–1025.

    Google Scholar 

  15. 15

    Ranki, A., Johansson, E. and Krohn, K. 1988. Interpretation of antibodies reacting solely with human retroviral core proteins. NEJM 318: 448–449.

    CAS  PubMed  Google Scholar 

  16. 16

    Delord, B., Ottmann, M., Schrive, M.H. et al. 1991. HIV-1 expression in 25 infected patients: A comparison of RNA PCR, p24 EIA in plasma and in situ hybridization in mononuclear cells, p. 113. In: Vol. I, Abstracts VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  17. 17

    Todak, G., Klein, E., Lange, M. et al. 1991. A clinical appraisal of the p24 antigen test, p. 326. In: Vol. I, Abstracts VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  18. 18

    Courouce, A., Muller, J. and Richard, B. 1986. False-positive Western blot reactions to human immunodeficiency virus in blood donors. Lancet II: 921–922.

    Google Scholar 

  19. 19

    Stricker, R.B., McHugh, T.M., Moody, D.J. et al. 1987. An AIDS-related Cytotoxic autoantibody reacts with a specific antigen on stimulated CD4 + T cells. Nature 327: 710–713.

    CAS  PubMed  Google Scholar 

  20. 20

    Chassagne, J., Verelle, P., Fonck, Y. et al. 1986. Detection of the lymphadeno-pathy-associated virus p18 in cells of patients with lymphoid diseases using a monoclonal antibody. Ann. Inst. Pasteur/Immunol. 137D: 403–408.

    CAS  Google Scholar 

  21. 21

    Parravicini, C.L., Klatzmann, D., Jaffray, P. et al. 1988. Monoclonal antibodies to the human immunodeficiency virus p18 protein cross-react with normal human tissues. AIDS 2: 171–177.

    CAS  PubMed  Google Scholar 

  22. 22

    Matsiota, P., Chamaret, S., Montagnier, L. et al. 1987. Detection of natural autoantibodies in the serum of anti-HIV positive-individuals. Ann. Inst. Pasteur/Immunol. 138: 223–233.

    CAS  Google Scholar 

  23. 23

    Popovic, M., Sarngadharan, M.G., Read, E. et al. 1984. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224: 497–500.

    CAS  Google Scholar 

  24. 24

    Wilber, J.C. 1991. New developments in diagnosing infections, p. 1–15. In: AIDS Clinical Review, P. Volbering, M. A. Jacobson (Eds.). Marcel Dekker Inc., New York.

    Google Scholar 

  25. 25

    Lundberg, G.D. 1988. Serological diagnosis of human immunodeficiency virus infection by Western blot testing. JAMA 260: 674–679.

    Google Scholar 

  26. 26

    Zolla-Pazner, S., Gorny, M.K. and Honnen, W.J. 1989. Reinterpretation of human immunodeficiency virus Western blot patterns. NEJM 320: 1280–1281.

    CAS  PubMed  Google Scholar 

  27. 27

    Burke, D.S. 1989. Laboratory diagnosis of human immunodeficiency virus infection. Clin. Lab. Med. 9: 369–392.

    CAS  PubMed  Google Scholar 

  28. 28

    Maskill, W.J. and Gust, I.D. 1992. HIV-1 testing in Australia. Australian Prescriber 15: 11–13.

    Google Scholar 

  29. 29

    DeCock, K.M., Selik, R.M., Soro, B. et al. 1991. AIDS surveillance in Africa: A reappraisal of case definitions. BMJ 303: 1185–1189.

    CAS  Google Scholar 

  30. 30

    Voevodin, A. 1992. HIV screening in Russia. Lancet 339: 1548.

    CAS  PubMed  Google Scholar 

  31. 31

    Working Group on AIDS Case Definition 1990. Epidemiol. Bull. 4: 9–11.

  32. 32

    Edwards, V.M., Mosley, J.W. and the Transfusion Safety Study Group. 1991. Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus. Am. J. Clin. Pathol. 91: 75–78.

    Google Scholar 

  33. 33

    CDC. 1989. Interpretation and use of the Western blot assay for serodiagnosis of human immunodeficiency virus type 1 Infections. MMWR 38 No. S-7: 1–7.

  34. 34

    Weiss, S.H., Goedert, J.J., Sarngadharan, M.G. et al. 1985. Screening test for HTLV-III (AIDS agent) antibodies. JAMA 253: 221–225.

    CAS  Google Scholar 

  35. 35

    Weiss, R. and Thier, S.O. 1988. HIV testing is the answer—what's the question? NEJM 319: 1010–1012.

    CAS  PubMed  Google Scholar 

  36. 36

    Burke, D.S., Brundage, J.F., Redfield, R.R. et al. 1988. Measurement of the false positive rate in a screening program for human immunodeficiency virus infections. NEJM 319: 961–964.

    CAS  PubMed  Google Scholar 

  37. 37

    Scarlatti, G.S., Lombardi, V., Plebani, A. et al. 1991. Polymerase chain reaction, virus isolation and antigen assay in HIV-1-antibody-positive mothers and their children. AIDS 5: 1173–1178.

    CAS  Google Scholar 

  38. 38

    Griner, P.F., Mayewski, R.J., Mushlin, A.I. et al. 1981. Selection and interpretation of diagnostic tests and procedures. Ann. Int. Med. 94 (Part 2): 559–563.

    Google Scholar 

  39. 39

    CDC. 1987. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. JAMA 258: 1143–1145.

  40. 40

    Conley, C.L. and Savarese, D. 1989. Biologic false-positive serologic tests for syphilis and other serologic abnormalities in autoimmune hemolytic anemia and thromobocytopenic purpura. Medicine 68: 67–84.

    CAS  PubMed  Google Scholar 

  41. 41

    Boue, F., Dreyfus, M., Bridley, F. et al. 1990. Lupus anticoagulant and HIV infection: A prospective study. AIDS 4: 467–471.

    CAS  PubMed  Google Scholar 

  42. 42

    Jaffe, J.H., Moore, J.D., Cone, E.J. et al. 1986. HTLV-III seropositivity in 1971–1972 parenteral drug abusers—a case of false positives or evidence of viral exposure? NEJM 314: 1387–1388.

    Google Scholar 

  43. 43

    Biggar, R.J., Gigase, P.L., Melbye, M. et al. 1985. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet II: 520–523.

    Google Scholar 

  44. 44

    Ternynck, T. and Avrameas, S. 1986. Murine natural monoclonal autoantibodies: a study of their polyspecificities and their affinities. Immunol. Rev. 94: 99–112.

    CAS  PubMed  Google Scholar 

  45. 45

    Pateraki, E., Kaklamani, E., Portocalas, K.R. et al. 1986. Autoantibodies in systemic lupus erythematosus and normal subjects. Clin. Rheumatol. 5: 338–345.

    CAS  PubMed  Google Scholar 

  46. 46

    Morton, D.L. and Malmgren, R.A. 1968. Human osteosarcomas: immunologic evidence suggesting an associated agent. Science 162: 1279–1281.

    CAS  PubMed  Google Scholar 

  47. 47

    Hirshaut, Y., Pei, D.T., Marcove, R.C. et al. 1974. Seroepidemiology of human sarcoma antigen (S1). NEJM 291: 1103–1107.

    CAS  PubMed  Google Scholar 

  48. 48

    Kurth, R., Teich, N.M., Weiss, R. et al. 1977. Natural human antibodies reactive with primate type-C viral antigens. Proc. Natl. Acad. Sci. 74: 1237–1241.

    CAS  PubMed  Google Scholar 

  49. 49

    Snyder, H.W. and Fleissner, E. 1980. Specificity of human antibodies to oncovirus glycoproteins: Recognition of antigen by natural antibodies directed against carbohydrate structures. Proc. Natl. Acad. Sci. 77: 1622–1626.

    CAS  PubMed  Google Scholar 

  50. 50

    Barbacid, M., Bolognesi, D. and Aaronson, S.A. 1980. Humans have antibodies capable of recognizing oncoviral glycoproteins: Demonstration that these antibodies are formed in response to cellular modification of glycoproteins rather than as consequence of exposure to virus. Proc. Natl. Acad. Sci. 77: 1617–1621.

    CAS  PubMed  Google Scholar 

  51. 51

    Essex, M., McLane, M.F., Lee, T.H. et al. 1983. Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science 220: 859–862.

    CAS  PubMed  Google Scholar 

  52. 52

    Novick, D.M., Des Jarlais, D.C., Kreek, M.J. et al. 1988. Specificity of antibody tests for human immunodeficiency virus in alcohol and parenteral drug abusers with chronic liver disease. Alcoholism Clin. Exp. Res. 12: 687–690.

    CAS  Google Scholar 

  53. 53

    European Collaborative Study. 1991. Children born to women with HIV-1 infection: natural history and risk of transmission. Lancet 337: 253–260.

  54. 54

    Beneviste, R.E., Ochs, H.D., Fischer, S.H. et al. 1986. Screening for antibodies to LAV/HTLV-III in recipients of immunoglobulin preparations. Lancet I: 1090–1092.

    Google Scholar 

  55. 55

    Burinsky, K.I., Chaplinskas, S.A., Syrtsev, V.A. et al. 1988. Reactivity to gag-and env-related sequences in immunoblot assay is not necessarily indicative of HIV infection. AIDS 2: 405–406.

    Google Scholar 

  56. 56

    Calabrese, L.H. 1988. Autoimmune manifestations of human immunodeficiency virus (HIV) infection. Clin. Lab. Med. 8: 269–279.

    CAS  PubMed  Google Scholar 

  57. 57

    Bonara, P., Maggioni, L. and Colombo, G. 1991. Anti-lymphocyte antibodies and progression of disease in HIV infected patients, p. 149. In: Vol. II, VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  58. 58

    Tumietto, F., Costigliola, P., Ricchi, E. et al. 1991. Anti-lymphocyte autoantibodies: evaluation and correlation with different stages of HIV infection, p. 149. In: Vol. II, VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  59. 59

    Morozov, V.A., Ilyinskii, P.O., Uckert, W.A. et al. 1989. Antibodies to structural and nonstructural gag-coded proteins of type-D retroviruses in

  60. 60

    Lucey, D.R., Hendrix, C.W., Andrzejewski, C. et al. 1992. Comparison by race of total serum IgG, IgA, and IgM with CD4 + T-cell counts in North American persons infected with the human immunodeficiency virus type 1. J. Acquir. Immun. Defic. Syndr. 5: 325–332.

    CAS  Google Scholar 

  61. 61

    Papadopulos-Eleopulos, E. 1988. Reappraisal of AIDS: Is the oxidation induced by the risk factors the primary cause? Med. Hypotheses 25: 151–162.

    CAS  PubMed  Google Scholar 

  62. 62

    Papadopulos-Eleopulos, E., Turner, V.F. and Papadimitriou, J. 1992. Kaposi's sarcoma and HIV. Med. Hypotheses 39: 22–29.

    CAS  PubMed  Google Scholar 

  63. 63

    Igel, H.J., Turner, H.C., Kotin, P. et al. 1969. Mouse leukaemia virus activation by chemical carcinogens. Science 166: 624–1626.

    Google Scholar 

  64. 64

    Sterk, C. 1988. Cocaine and HIV seropositivity. Lancet I: 1052–1053.

    Google Scholar 

  65. 65

    Kion, T.A. and Hoffmann, G.W. 1991. Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. Science 253: 1138–1140.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Conley, L.J. and Holmerg, S.D. 1992. Transmission of AIDS from blood screened negative for antibody to the human immunodeficiency virus. NEJM 326: 1499.

    CAS  PubMed  Google Scholar 

  67. 67

    Burgher, H., Weiser, B., Robinson, W.S. et al. 1985. Transient antibody to lymphadenopathy-associated/human T-lymphotrophic virus type III and T-lymphocyte abnormalities in the wife of a man who developed the acquired immunodeficiency syndrome. Ann. Int. Med. 103: 545–547.

    Google Scholar 

  68. 68

    Esteva, M.H., Blasini, A.M., Ogly, D. and Rodriguez, M. A. 1992. False positive results from antibody to HIV in two men with systemic lupus erythre-matosus. Ann. Rhem. Dis. 51: 1071–1073.

    CAS  Google Scholar 

  69. 69

    Dummer, J.S., Erb, S., Breinig, M.K. et al. 1989. Infection with human immunodeficiency virus in the Pittsburgh transplant population. Transplantation 47: 134–139.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Pitchenik, A.E., Burr, J., Suarez, M. et al. 1987. Human T-cell lymphotrophic virus-Ill (HTLV-III) seropositivity and related disease among 71 consecutive patients in whom tuberculosis was diagnosed. Am. Rev. Respir. Dis. 135: 875–879.

    CAS  PubMed  Google Scholar 

  71. 71

    Nzilambi, N., Mann, J.M., Francis, H. et al. 1986. Seroprevalence among tuberculosis patients in Zaire. In: Abstracts II International AIDS Conference, Paris, No.105:S17b.

    Google Scholar 

  72. 72

    St. Louis, M.E., Rauch, K.J., Peterson, L.R. et al. 1990. Seroprevalence rates of human immunodeficiency virus infection at sentinel hospitals in the United States. NEJM 323: 213–218.

    CAS  PubMed  Google Scholar 

  73. 73

    Chamberland, M., Conley, L. and Dondero, T. 1988. Epidemiology of hetero-sexually acquired AIDS—United States, p. 264. In: Abstacts IV International AIDS Conference, Stockholm.

    Google Scholar 

  74. 74

    New York City AIDS Surveillance Report, January-March 1992.

  75. 75

    Rodriquez, L., Dewhurst, S., Sinangil, F. et al. 1985. Antibodies to HTLV-III/ LAV among aboriginal Amazonian Indians in Venezuela. Lancet II: 1098–1100.

    Google Scholar 

  76. 76

    Volsky, D.J., Wu, Y.T., Stevenson, M. et al. 1986. Antibodies to HTLV-III/ LAV in Venezuelan patients with acute malarial syndromes. NEJM 314: 647.

    CAS  PubMed  Google Scholar 

  77. 77

    Rous, P. 1911. A Sarcoma of the fowl transmissible by an agent separable from the tumor cells. J. Exp. Med. 13: 397–411.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Toplin, I. 1973. Tumor virus purification using zonal rotors. Spectra No. 4: 225–235.

  79. 79

    Temin, H.M. and Baltimore, D. 1972. RNA-directed DNA synthesis and RNA tumor viruses. Adv. Vir. Res. 17: 129–186.

    CAS  Google Scholar 

  80. 80

    RNA tumor viruses. 1982. Weiss, R., Teich, N., Varmus, J., Coffin, J. (Eds.). Cold Spring Harbor Laboratory. Cold Spring Harbor, New York.

  81. 81

    Bader, J.P. 1975. Reproduction of RNA tumor viruses, p. 253–331. In: Comprehensive Virology Vol. 4. H. Fraenkel-Conrat, R.R. Wagner (Eds.). Plenum Press, New York.

    Google Scholar 

  82. 82

    Sinoussi, F., Mendiola, L., Chermann, J.C. et al. 1973. Purification and partial differentiation of the particles of murine sarcoma virus (M. MSV) according to their sedimentation rates in sucrose density gradients. Spectra No. 4: 237–243.

  83. 83

    Amiesen, J.C. and Capron, A. 1991. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol. Today 12: 102–105.

    Google Scholar 

  84. 84

    Wyllie, A.H., Kerr, J.F.R. and Currie, A.R. 1980. Cell death: The significance of apoptosis. Int. Rev. Cytol. 68: 252–306.

    Google Scholar 

  85. 85

    Hoxie, J.A., Fitzharris, T.P., Youngbar, P.R. et al. 1987. Nonrandom association of cellular antigens with HTLV-III virions. Hum. Immunol. 18: 39–52.

    CAS  PubMed  Google Scholar 

  86. 86

    McKeating, J.A. and Moore, J.P. 1991. HIV intectivity. Nature 349: 660.

    CAS  PubMed  Google Scholar 

  87. 87

    Masquelier, B., Combeau, T. and Poveda, J. 1991. In vitro assays show a dissociation of reverse transcriptase activity and core antigen (p24) production in two HIV-1 isolates from a patient receiving long-term treatment with zidovu-dine (ZDV). J. Acquir. Immun. Defic. Syndr. 4: 499–505.

    CAS  Google Scholar 

  88. 88

    Grunow, R., Valentin, A., Fenyo, E.M. et al. 1991. Release of HIV-1 core protein from infected cells independent of infectious virus particles, p. 157. In: Vol. I, Abstracts VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  89. 89

    Tedder, R.S., Semple, M.G., Tenant-Flowers, M. et al. 1992. HIV, AIDS, and zidovudine. Lancet 339: 805–806.

    CAS  PubMed  Google Scholar 

  90. 90

    Lemaître, M., Guétard, D., Hénin, Y. et al. 1990. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res. Virol. 141: 5–16.

    PubMed  Google Scholar 

  91. 91

    Boulerice, F., Bour, S., Geleziunas, R. et al. 1990. High frequency of isolation of defective human immunodeficiency virus type 1 and heterogeneity of viral gene expression in clones of infected U-937 cells. J. Virol. 64: 1745–1755.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Ehrnst, A., Sonnerborg, A., Bergdahl, S. and Strammegard, O. 1988. Efficient isolation of HIV from plasma during different stages of HIV infection. J. Med. Virol. 26: 23–32.

    CAS  PubMed  Google Scholar 

  93. 93

    Learmont, J., Tindall, B., Evans, L. et al. 1992. Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 340: 863–867.

    CAS  PubMed  Google Scholar 

  94. 94

    Popovic, M., Sarngadharan, M.G., Read, E. et al. 1984. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224: 497–500.

    CAS  Google Scholar 

  95. 95

    Gallo, R.C., Sarin, P.S. and Wu, A.M. 1973. On the nature of the nucleic acids and RNA dependent DNA polymerase from RNA tumor viruses and human cells, p. 13–34. In: Possible Episomes in Eukaryotes. L.G. Silvestri (Ed.). North-Holland Publishing Company, Amsterdam.

    Google Scholar 

  96. 96

    Whitkin, S.S., Higgins, P.J. and Bendich, A. 1978. Inhibition of reverse transcriptase and human sperm DNA polymerase by anti-sperm antibodies. Clin. Exp. Immunol. 33: 244–251.

    Google Scholar 

  97. 97

    Tomley, F.M., Armstrong, S.J., Mahy, B.W.J. and Owen, L.N. 1983. Reverse transcriptase activity and particles of retroviral density in cultured canine lymphosarcoma supernatants. Br. J. Cancer 47: 277–284.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

    Weissbach, A., Baltimore, D., Bollum, F. et al. 1975. Nomenclature of euka-ryotic DNA polymerases. Science 190: 401–402.

    CAS  PubMed  Google Scholar 

  99. 99

    Gallo, R. ., Wong-Staal, F., Reitz, M. et al. 1976. Some evidence for infectious type-C virus in humans, p. 385–407. In: Animal Virology. D. Baltimore, A.S. Huang, C.F. Fox (Eds.). Academic Press Inc., New York.

    Google Scholar 

  100. 100

    Panem, S., Prochownik, E.V., Reale, F.R. et al. 1975. Isolation of type-C virions from a normal human fibroblast strain. Science 189: 297–299.

    CAS  PubMed  Google Scholar 

  101. 101

    Panem, S., Prochownik, E.V., Knish, W.M. and Kirsten, W.H. 1977. Cell generation and type-C virus expression in the human embryonic cell strain HEL-12. J. Gen. Virol. 35: 487–495.

    CAS  PubMed  Google Scholar 

  102. 102

    Panem, S. 1979. C-type virus expression in the placenta. Curr. Top. Pathol. 66: 175–189.

    CAS  PubMed  Google Scholar 

  103. 103

    Sarngadharan, M.G., Robert-Guroff, M. and Gallo, R.C. 1978. DNA polymerases of normal and neoplastic mammalian cells. Biochim. Biophys. Acta. 516: 419–487.

    CAS  PubMed  Google Scholar 

  104. 104

    Klatzmann, D., Barré-Sinoussi, P., Nugeyre, M. T. et al. 1984. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science 225: 59–63.

    CAS  Google Scholar 

  105. 105

    Montagnier, L. 1985. Lymphadenopathy-associated virus:From molecular biology to pathogenicity. Ann. Int. Med. 103: 689–693.

    CAS  PubMed  Google Scholar 

  106. 106

    Gendelman, H.E., Orenstein, J.M., Martin, M.A. et al. 1988. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J. Exp. Med. 167: 1428–1441.

    CAS  PubMed  Google Scholar 

  107. 107

    Gelderblom, H.R., Hausmann, E.H.S., Özel, M. et al. 1987. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virol. 156: 171–176.

    CAS  Google Scholar 

  108. 108

    Gelderblom, H., Reupke, H., Winkel, T. et al. 1987. MHC-antigens: Constituents of the envelopes of human and simian immunodeficiency viruses. Z. Naturforsch. 42C: 1328–1334.

    Google Scholar 

  109. 109

    Gelderblom, H.R., Reupke, H. and Pauli, G. 1985. Loss of envelope antigens of HTLV-III/LAV, a factor in AIDS pathogenesis? Lancet 11: 1016–1017.

    Google Scholar 

  110. 110

    Neidrig, M., Rabanus, J.P., L'Age Stehr, J. et al. 1988. Monoclonal antibodies directed against human immunodeficiency virus (HIV) gag proteins with specificity for conserved epitopes in HIV-1, HIV-2 and simian immunodeficiency virus. J. Gen. Virol. 69: 2109–2114.

    Google Scholar 

  111. 111

    Gelderblom, H.R., Özel, M., Hausmann, E.H.S. et al. 1988. Fine structure of human immunodeficiency virus (HIV), immunolocalization of structural proteins and virus-cell relation. Micron Microsc. 19: 41–60.

    Google Scholar 

  112. 112

    Meerloo, T., Parmentier, H.K., Osterhaus, A. et al. 1992. Modulation of cell surface molecules during HIV-1 infection of H9 cells. An immunoelectron microscopic study. AIDS 6: 1105–1116.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113

    Lecatsas, G. and Taylor, M.B. 1986. Pleomorphism in HTLV-III, the AIDS virus. S. Afr. Med. J. 69: 793–794.

    PubMed  Google Scholar 

  114. 114

    Hockley, D.J., Wood, R.D., Jacobs, J.P. et al. 1988. Electron microscopy of human immunodeficiency virus. J. Gen. Virol. 69: 2455–2469.

    PubMed  Google Scholar 

  115. 115

    Dourmashkin, R.R., O'Toole, C.M., Bucher, D. and Oxford, J.S. 1991. The presence of budding virus-like particles in human lymphoid cells used for HIV cultivation, p. 122. In: Vol. I, Abstracts VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  116. 116

    Brennan, J.K., Lichtman, M.A., Chamberlain, J.K. and Leblond, P. 1976. Isolation of variant lymphoma cells with reduced growth requirements for extracellular calcium and magnesium and enhanced oncogenicity. Blood 47: 447–459.

    CAS  PubMed  Google Scholar 

  117. 117

    Garry, R.F., Fermin, C.D., Hart, D.J. et al. 1990. Detection of a human intracisternal A-type retroviral particle antigenically related to HIV. Science 250: 1127–1129.

    CAS  PubMed  Google Scholar 

  118. 118

    Armstrong, J.A. and Home, R. 1984. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet 11: 370–372.

    Google Scholar 

  119. 119

    Tenner-Racz, K., Racz, P., Bofill, M. et al. 1986. HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS. Am. J. Pathol. 123: 9–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Le Tourneau, A., Audouin, J., Diebold, J. et al. 1986. LAV-like viral particles in lymph node germinal centers in patients with the persistent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex. Hum. Pathol. 17: 1047–1053.

    CAS  PubMed  Google Scholar 

  121. 121

    O'Hara, C.J., Groopmen, J.E. and Federman, M. 1988. The ultrastructural and immunohistochemical demonstration of viral particles in lymph nodes from human immunodeficiency virus-related lymphadenopathy syndromes. Hum. Pathol. 19: 545.

    CAS  PubMed  Google Scholar 

  122. 122

    Culliton, B.J. 1992. The mysterious virus called “isn't”. Nature 358: 619.

    CAS  PubMed  Google Scholar 

  123. 123

    Chiodi, F., Albert, J., Olausson, E. et al. 1988. Isolation frequency of human immunodeficiency virus from cerebrospinal fluid and blood of patients with varying severity of HIV infection. AIDS Res. Hum. Retroviruses 4: 351–358.

    CAS  PubMed  Google Scholar 

  124. 124

    Salahuddin, S.Z., Groopman, J.E., Markham, P.D. et al. 1984. HTLV-III symptom-free seronegative persons. Lancet II: 1418–1420.

    Google Scholar 

  125. 125

    Boussin, F., Rey, E., Dormont, D. et al. 1988. Isolation of HIV in a seronegative demented patient without symptoms of immune deficiency. Cancer Detect. Prev. 12: 257–265.

    CAS  PubMed  Google Scholar 

  126. 126

    Bayliss, G.J., Jesson, W.J., Evans, B.A. et al. 1989. Isolation of HIV-1 from small volumes of heparinized whole blood. AIDS 3: 45–49.

    CAS  PubMed  Google Scholar 

  127. 127

    Fiore, J.R., Angarano, G., Fico, C. et al. 1990. Cell cultures from small amounts of heparinized whole blood enhance HIV-1 isolation rate. AIDS 4: 1295–1296.

    CAS  PubMed  Google Scholar 

  128. 128

    Schüpbach, J., Jendis, J.B., Bron, C. et al. 1992. False-positive HIV-1 virus cultures using whole blood. AIDS 6: 1545–1546.

    PubMed  Google Scholar 

  129. 129

    Hart, C., Spira, T., Moore, J. et al. 1988. Direct detection of HIV RNA expression in seropositive subjects. Lancet II: 596–599.

    Google Scholar 

  130. 130

    Aaronson, S.A., Todaro, G.J. and Scholnick, E.M. 1971. Induction of murine C-type viruses from clonal lines of virus-free BALB/3T3 cells. Science 174: 157–159.

    CAS  PubMed  Google Scholar 

  131. 131

    Hirsch, M.S., Phillips, S.M., Solnik, C. et al. 1972. Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions in vitro. Proc Nat. Acad. Sci. 69: 1069–1072.

    CAS  PubMed  Google Scholar 

  132. 132

    Toyoshima, K. and Vogt, P.K. 1969. Enhancement and inhibition of avian sarcoma viruses by polycations and polyanions. Virol. 38: 414–426.

    CAS  Google Scholar 

  133. 133

    Nakamura, N., Sugino, H., Takahara, K. et al. 1991. Endogenous retroviral LTR DNA sequences as markers for individual human chromosomes. Cytogenet. Cell Genet. 57: 18–22.

    CAS  PubMed  Google Scholar 

  134. 134

    Varmus, H. and Brown, P. 1989. Retroviruses, p. 53–108. In: Mobile DNA. D. E. Berg, M. M. Howe (Eds.). American Society for Microbiology. Washington, D. C.

    Google Scholar 

  135. 135

    Weiss, R.A., Friis, R.R., Katz, E. et al. 1971. Induction of avian tumor viruses in normal cells by physical and chemical carcinogens. Virol. 46: 920–938.

    CAS  Google Scholar 

  136. 136

    Temin, H.M. 1974. On the origin of RNA tumor viruses. Harvey Lect 69: 173–197.

    Google Scholar 

  137. 137

    Wain-Hobson, S. and Myers, G. 1990. Too close for comfort. Nature 347: 18.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138

    Genetics of RNA tumour viruses. 1973. p. 656–699. In: The molecular biology of tumour viruses. J. Tooze (Ed.). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

  139. 139

    Saag, M.S., Hahn, B.H., Gibbons, J. et al. 1988. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature 334: 440.

    CAS  Google Scholar 

  140. 140

    Marx, J.L. 1988. The AIDS virus can take on many guises. Science 241: 1039–1040.

    CAS  PubMed  Google Scholar 

  141. 141

    von Briesen, H., Becker, W.B., Henco, K. et al. 1987. Isolation frequency and growth properties of HIV-variants:Multiple simultaneous variants in a patient demonstrated by molecular cloning. J. Med. Virol. 23: 51–66.

    CAS  PubMed  Google Scholar 

  142. 142

    Bolton, V., Pedersen, N.C., Higgins, J. et al. 1987. Unique p24 epitope marker to identify multiple human immunodeficiency virus variants in blood from the same individuals. J. Clin. Microbiol. 25: 1411–1415.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143

    Wain-Hobson, S. 1989. HIV genome variability in vivo. AIDS 3: S13–S18.

    PubMed  Google Scholar 

  144. 144

    Innocenti, P., Ottmann, M., Morand, P. et al. 1992. HIV-1 blood monocytes: Frequency of detection of proviral DNA using PCR in comparison with the total CD4 count. AIDS Res. Hum. Retroviruses 8: 261–268.

    CAS  PubMed  Google Scholar 

  145. 145

    Meyerhans, A., Cheynier, R., Albert, J. et al. 1989. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell 58: 901–910.

    CAS  Google Scholar 

  146. 146

    Robey, W.G., Nara, P.L., Poore, C.M. et al. 1987. Rapid assessment of relationships among HIV isolates by oligopeptide analyses of external envelope glycoproteins. AIDS Res. Hum. Retroviruses 3: 401–408.

    CAS  PubMed  Google Scholar 

  147. 147

    Shaw, G.M., Hahn, B.H., Suresh, K.A. et al. 1984. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science 226: 1165–1171.

    CAS  Google Scholar 

  148. 148

    Simmonds, P., Balfe, P., Peutherer, J.F. et al. 1990. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J. Virol. 64: 864–872.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149

    Van Voorhis, B.J., Martinez, A., Mayer, K. and Anderson, D.J. 1991. Detection of human immunodeficiency virus type 1 in semen from seropositive men using culture and polymerase chain reaction deoxyribonucleic acid amplification techniques. Fertil. Steril. 55: 588–594.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150

    Deter, C., Agut, H. and Garbarg-Chenon, A. 1992. Multicentre quality control of polymerase chain reaction for detection of HIV DNA. AIDS 6: 659–663.

    Google Scholar 

  151. 151

    Becker, J.L., Kazan, U., Nugeyre, M.T. et al. 1986. Infection of insect lines by HIV, agent of AIDS, and evidence for HIV proviral DNA in insects from Central Africa. C. R. Acad. Sci. Paris. 300: 303–306.

    Google Scholar 

  152. 152

    Arya, S.K., Gallo, R.C., Hahn, B.H. et al. 1984. Homology of genome of AIDS-associated virus with genomes of human T-Cell leukemia viruses. Science 225: 927–930.

    CAS  Google Scholar 

  153. 153

    Mager, D.L. and Freeman, J.D. 1987. Human endogenous retroviruslike genome with type C pol sequences and gag sequences related to human T-cell lymphotropic viruses. J. Virol. 61: 4060–4066.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Banki, K., Maceda, J., Hurley, E. et al. 1992. Human T-cell lymphotropic virus (HTLV)-related endogenous sequence, HRES-1 encodes a 28-kDa protein:a possible autoantigen for HTLV-I gag-reactive autoantibodies. Proc. Natl. Acad. Sci. 89: 1939–1943.

    CAS  PubMed  Google Scholar 

  155. 155

    Webster, A.D.B., Dalgleish, A.G., Beattie, R. et al. 1986. Isolation of retroviruses from two patients with “common variable” hypogammaglobulinaemia. Lancet I: 581–582.

    Google Scholar 

  156. 156

    Ciampolillo, A., Marini, V. and Buscema, M. 1989. Retrovirus-like sequences in Graves' disease: Implications for human autoimmunity. Lancet I: 1096–1100.

    Google Scholar 

  157. 157

    Horwitz, M.S., Boyce-Jacino, M.T. and Faras, A.J. 1992. Novel human endogenous sequences related to human immunodeficiency virus type 1. J. Virol. 66: 2170–2179.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. 158

    Farzadegan, H., Polls, M., Wolinsky, S.M. et al. 1988. Loss of human immunodeficiency virus type 1 (HIV-1) antibodies with evidence of viral infection in asymptomatic homosexual Men. Ann. Int. Med. 108: 785–790.

    CAS  PubMed  Google Scholar 

  159. 159

    Horsburgh, C.R., Ou, C.Y., Holmberg, S.D. et al. 1989. Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. NEJM 321: 1678–1680.

    Google Scholar 

  160. 160

    Mikovits, J.A., Lohrey, N., Schuloff, R., Ruscetti, F. 1991. Immune activation of latent HIV-1 expression in monocyte/macrophages, p. 151. In: Vol. I, Abstracts VII International Conference on AIDS, Florence, Italy.

    Google Scholar 

  161. 161

    Vartanian, J.P., Meyerhans, A., Henry, M. and Wain-Hobson, S. 1992. High-resolution structure of an HIV-1 quasispecies: Identification of novel coding sequences. AIDS 6: 1095–1098.

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Papadopulos-Eleopulos, E., Turner, V. & Papadimitriou, J. Is a Positive Western Blot Proof of HIV Infection?. Nat Biotechnol 11, 696–707 (1993). https://doi.org/10.1038/nbt0693-696

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing