Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees.
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.
Robinson
W E
WE
Department of Pathology, Vanderbilt University, Nashville, TN 37232.
Montefiori
D C
DC
Mitchell
W M
WM
Prince
A M
AM
Alter
H J
HJ
Dreesman
G R
GR
Eichberg
J W
JW
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D003602:Cytotoxicity, Immunologic; D004546:Elapid Venoms / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology*; D007116:Immunization, Passive; D002679:Pan troglodytes; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism
D004546:Elapid Venoms; D012194:RNA-Directed DNA Polymerase