Antibody-Dependent Enhancement of Human Immunodeficiency Virus Type 1 (HIV-1) Infection in vitro by Serum from HIV-1-Infected and Passively Immunized Chimpanzees

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 12; pp. 4710 - 4714
• Main Authors: Robinson, W. Edward, Montefiori, David C., Mitchell, William M., Prince, Alfred M., Alter, Harvey J., Dreesman, Gordon R., Eichberg, Jorg W.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-06-1989; National Acad Sciences
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - immunology; AIDS/HIV; Animals; Antibodies; Antibody-Dependent Cell Cytotoxicity; Biological and medical sciences; Blocking antibodies; Cell lines; Chimpanzees; Cobra venoms; Cytotoxicity, Immunologic; Elapid Venoms - immunology; Fluorescent Antibody Technique; HIV 1; HIV-1 - enzymology; HIV-1 - immunology; human immunodeficiency virus 1; Humans; Immunization, Passive; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Medical sciences; Pan troglodytes; RNA-Directed DNA Polymerase - metabolism; Vaccination; Viruses; Animal model; HIV-1 virus; Antibody; Cytotoxicity test; Monkey; Retroviridae; Stimulation; Complement; Virus; Infection; Vertebrata; Mammalia; Venom; Primates; Serum; Human immunodeficiency virus; Passive immunization
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.12.4710

Based on recent reports of antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected humans, sera from HIV-1 antibody-positive chimpanzees (Pan troglodytes) was evaluated for enhancing activity in an in vitro infection assay that uses MT-2 cells (a human lymphoblastoid cell line). Although fresh chimpanzee serum was found to have pronounced infection-enhancing properties in the absence of antibody to HIV-1, this effect was abolished by heat inactivation (57 degrees C, 1 hr) or treatment with cobra venom anticomplementary protein. Heat-inactivated, HIV-1 antibody-positive chimpanzee serum could enhance HIV-1 infection of MT-2 cells in vitro when combined with fresh, normal human serum. By serial serum samples from three HIV-1-infected chimpanzees, HIV-1 antibody-positive chimpanzees are shown to develop enhancing antibodies early in infection (2 mo postchallenge), whereas neutralizing antibodies develop later. Over the course of HIV-1 infection, this enhancing activity decreases while neutralizing activity increases, suggesting a possible role for enhancing and neutralizing activities in HIV-1 pathogenesis. The enhancing activity of an IgG fraction used to passively immunize chimpanzees against HIV-1 infection is shown to be present at dilutions as high as 1:65,000, offering an interesting possible reason for the failure of passive immunization to protect chimpanzees from HIV infection. These results suggest that serum from HIV-1-immunized chimpanzees might be tested to determine whether current HIV-1 candidate vaccines induce production of antibodies that mediate antibody-dependent enhancement of HIV-1 infection in this in vitro assay.