Induction in Chimpanzees of Antibodies Inhibiting Receptor-Mediated Cell Fusion by HIV Glycoprotein

Abstract

Cell fusion of HTLV-IIIB-infected EBV-transformed B cells and CD4+ T cells was inhibited by sera from eight of nine HIV infected chimpanzees. Syncytia formation was reduced by sixty percent relative to control after only 5 minutes of preincubation of the HIV infected cells with immune primate serum, indicating that these antibodies have high affinity for HIV protein on the surface of infected cells. Serum dilutions that blocked formation of syncytia irreversibly within 24 hrs also blocked expression of HIV antigens by the target CD4+ cells. Three of four animals inoculated with the LAV or HTLV-IIIB strain of HIV developed antibodies inhibiting CD4-dependent cell fusion by HIV glycoprotein (CFI-antibodies) 2-3 months after inoculation coincident with development of HIV specific IgG antibodies. Similar early CFI-antibody responses occurred in two second passage chimpanzees. In contrast, a chimpanzee infected with a third passage of LAV had a delayed CFI-antibody response, indicating that variants of HIV with divergent CFI epitopes did eventually emerge. Delayed development of CFI-antibodies (6-11 months after inoculation) relative to HIV specific IgG ELISA antibody was also seen in a chimpanzee on primary passage and a chimpanzee on second passage of HTLV-IIIB. No CFI-antibodies were detected in a chimpanzee following inoculation with human brain tissue, while antibodies to other structural proteins were recognized by immunoblotting. These results indicate that changes in CFI epitopes occur under immune pressure and that the appearance of CFI-antibodies depends on the time after infection and on the degree to which CFI epitopes of the inoculum strain diverge from those of the test strain.