Summary
Human antibodies to HIV antigens expressed on the surface of infected cells may inhibit cell fusion with uninfected CD 4-positive cells and mediate killing of the infected cells by effector cells bearing the Fc receptor.
Sequential sera from ten HIV-antibody seroconverted men, of which five progressed to ARC or AIDS (CDC stage IV) during the follow-up period of two years, were tested for the ability to inhibit CD 4-dependent cell fusion, (CFI) and to mediate antibody-dependent cellular cytotoxicity (ADCC).
Nine patients developed HIV-specific ADCC and seven CFI-antibodies using the HIV strain HTLV-IIIB as target antigen. These antibodies appeared approximately at the same time 2–12 months after primary infection, defined as antibody seroconversion or antigenaemia. ADCC antibodies were detectable at higher titers as compared to CFI-antibodies. All sera of asymptomatic individuals (CDC stage II and III) were CFI antibody positive and had a higher mean ADCC titer as compared to sera from patients progressing to AIDS or ARC.
ADCC and CFI antibodies coincided in some cases in the complete absence of core antibodies. Because the relationship between ADCC and CFI was not exclusive it is concluded that distinct domains of the HIV envelope induce natural antibodies mediating ADCC and CFI.
Similar content being viewed by others
References
Falk Jr LM, Paul DA, Landay A, Kessler H (1987) HIV isolation from plasma of HIV-infected persons. N Engl J Med 316: 1547
Gaines H, Albert J, Von Sydow M, Sönnerborg, Chiodi F, Ehrnst F, Strannegård O, Åsjö B (1987) HIV antigenaemia and virus isolation from plasma during primary HIV infection. Lancet 1: 1317
Goudsmit J, Paul DA, Lange JMA et al (1986) Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet ii: 177–180
Goudsmit J, Lange JMA, Paul DA, Dawson GJ (1987) Antigenaemia and antibody titers to core and envelope antigens in AIDS, AIDS-related complex and subclinical human inmmunodeficiency virus infection. J Infect Dis 155: 558–560
Goudsmit J, Lange JMA, Krone WJA et al (1987) Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy. J Virol Methods 17: 19–34
Goudsmit J, Boucher CAB, Meloen RH, Epstein LG, Smit L, vd Hoek L, Bakker M (1988) Human antibody response to a strain-specific HIV-1 gp 120 epitope associated with cell fusion inhibition. AIDS 2: 157–164
Goudsmit J, Thiriart C, Smit L, Bruck C, Gibbs GJ (1987) Temporal development of cross-neutralization between HTLV-IIIB and HTLV-III RF in experimentally infected chimpanzees. Vaccine 6: 229–232
Hecht F, Morgan R, Kaiser-McCraw Hecht B, Smith S (1984) Common region on chromosome 14 in T-cell leukemia and lymphoma. Science 226: 1445–1446
Hoxie JA, Alpers JD, Rackowski LJ, Huebner K, Haggarty BS, Cedarbaum AJ, Reed JC (1986) Alterations in T 4 (CD 4) protein and mRNA synthesis in cells infected with HIV. Science 234: 1123–1127
Kennedy-Stoskopf S, Narayan O (1986) Neutralizing antibodies to Visna Lentivirus: mechanism of action and possible role in virus persistence. J Virol 59: 1–44
Lange JMA, Paul DA, Huisman HG et al (1986) Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. Br Med J 293: 1459–1462
Lange JMA, Coutinho RA, Krone JMA et al (1986) Distinct IgG recognition patterns during progression of sublinical and clinical infection with lymphadenopathy associated virus/human T lymphotropic virus. Br Med J 292: 228–230
Lange JMA, vd Berg H, Dooren LJ et al (1986) HTLV-III/LAV infection in nine children infected by a single plasma donor: clinical outcome and recognition patterns of viral proteins. J Infect Dis 154: 171–174
Lange JMA, Paul DA, de Wolf F et al (1987) Expression, antibody production and immune complex formation in human immunodeficiency virus infection. AIDS 1: 15–20
Lifson JD, Feinberg MB, Reyes GR, Rabin L, Banapour B, Chakrabarti et al (1986) Induction of CD 4-dependent cell fusion by the HTLV III-LAV envelope glycoprotein. Nature 323: 725–728
Lifson JS, Coutré E, Huang E, Engleman EG (1986) Role of envelope glycoprotein carbohydrate in human immunodeficiency virus (HIV) infectivity and virus-induced cell fusion. J Exp Med 164: 2101–2106
Ljunggren K, Böttiger B, Biberfeld G, Karlson A, Fenyö EM, Jondal M (1987) Antibody-dependent cellular cytotoxicity (ADDC)— inducing antibodies against Human Immunodeficiency Virus (HIV): presence at different clinical stages. J Immunol 139: 2263–2267
Ljunggren K, Chiodi F, Biberfeld G, Norrby E, Jondal M, Fenyö EM (1987) Lack of cross-reaction in antibody-dependent cellular cytotoxicity between HIV and HIV related West African strains. Submitted
Ljunggren K, Fenyö EM, Biberfeld G, Jondal M (1987) Detection of antibodies which mediate human immunodeficiency virus-specific cellular cytotoxicity (ADCC) in vitro. J Immunol Methods, in press
Lyerly HK, Matthews TJ, Langlois AJ, Bolognesi DP, Weinhold KJ (1987) Human T-cell lymphotropic virus IIIb glycoprotein (gp 120) bound to CD 4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc Natl Acad Sci USA 84: 4601–4605
Matthews TJ, Langlois AJ, Robey WG et al (1986) Restricted neutralization of divergent human T-lymphotropic virus type III isolated by antibodies to the major envelope glycoprotein. Proc Natl Acad Sci USA: 9709–9713
McDougal JSM, Kennedy MS, Sligh JM, Cort SP, Mawle A, Nicholson JMA (1986) Binding of HTLV-III/LAV to T 4+ T cells by a complex of the 110 K viral protein and the T 4 molecule. Science 231: 382–385
McDougal JSM, Nicholson JKA, Cross GD, Cort SP, Kennedy MS, Mawle AC (1986) Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD 4 (T 4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol 137: 2937–2944
Melbey M, Biggar AJ, Ebbesen P et al (1986) Long term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunological and clinical abnormalities. Ann Intern Med 104: 496–500
Montagnier L, Clavel K, Krust B, Chamaret S, Rey F, Barré-Sinoussi F, Chermann JC (1985) Identification and antigenicity of the major envelope glycoprotein of lymphadenopathy-associated virus. Virology 144: 283–289
Robert-Guroff M, Brown M, Gallo RC (1985) HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature 316: 69–71
Rook AH, Lane Clifford H, Folks T, McCoy S, Alter H, Fauci AS (1987) Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV infected T cells. J Immunol 138: 1064–1067
Sattentau QJ, Dalgleish AG, Weiss RA, Beverly PCL (1986) Epitopes of the CD 4 antigen and HIV infection. Science 234: 1123–1127
Schwartz K, Visscher BR, Detels R, Taylor J, Nishanian P, Fahey JC (1985) Immunological changes in lymphadenopathy virus positive and negative symptomless male homosexuals: two years of observation. Lancet ii: 831–832
Schüpbach J, Heller O, Vogt M, Lüthy R, Joller H, Oelz O, Popovic M, Sarngadharen MG, Gallo RC (1985) Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS. N Engl J Med 312: 265–270
Sodroski J, Goh WC, Rosen C, Cambell K, Haseltine WA (1986) Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322: 470–474
Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engelman E (1987) pH-Independent HIV entry into CD 4-positive T cells via virus envelope fusion to the plasma membrane. Cell 49: 659–668
Sündström C, Nilsson K (1976) Establishment and characterization of a human histiocytic lymphoma cell line (U 937). Int J Cancer 17: 565
Tersmette T, Miedema F, Huisman HG, Goudsmit J, Melief CJM (1985) Productive HTLV-III infection of human B cell lines. Lancet i: 815–816
Ujhelyi E, Büki B, Salavecz V et al (1987) A simple method for detecting HIV antibodies hidden in circulating immune complexes. AIDS 1: 161–165
Weber JN, Wedworth J, Roger LA et al (1986) Three-year prospective study of HTLV-III/LAV infection in homosexual men. Lancet i: 1178–1182
Weber JN, Clapham PR, Weiss RA, Parker D, Roberts C, Duncan J, Weller I, Carne CA, Tedder RS, Pinching AJ, Cheingsong-Popov R (1987) Human immunodeficiency virus infection in two cohorts of homosexual men: neutralizing sera and association of anti-gag antibody with prognosis. Lancet i: 119–122
Weiss RA, Clapham PR, Cheingsong-Popov R, Dalgleish AG, Carne CA, Weller IVD et al (1985) Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature 316: 69–71
Weiss RA, Clapham PR, Weber JN, Dalgleish AG, Lasky LA, Berman PW (1986) Variable and conserved neutralization antigens on human immunodeficiency virus. Nature 324: 572
de Wolf F, Goudsmit J, Paul DA et al (1987) Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia. Br Med J 295: 569–572
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goudsmit, J., Ljunggren, K., Smit, L. et al. Biological significance of the antibody response to HIV antigens expressed on the cell surface. Archives of Virology 103, 189–206 (1988). https://doi.org/10.1007/BF01311092
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01311092