IDENTIFICATION OF COMPLEMENT ACTIVATION SITES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GLYCOPROTEIN GP120

Recombinant glycoprotein 120 (rgp120) of human immunodeficiency virus type-1 (HIV-1) activates the human complement system in the absence of anti-gp120 antibodies. HIV-1 glycoprotein gp120 can dissociate from t he viral envelope either spontaneously or after binding of HIV-1 to th e CD4 molecule. As a consequence, gp120 can circulate in the patient's serum and attach to the surface of uninfected CD4(+) T cells. Complem ent activation by cell-bound HIV-1 glycoprotein gp120 with subsequent opsonization may represent a mechanism for the elimination of uninfect ed CD4(+) cells by the reticuloendothelial system, thereby enhancing t he progression of HIV disease. In the current study, the complement pr oteins C4, C3, C5, C9, and properdin were found to bind to a synthetic peptide covering positions 233-251 of the gp120(BRU) sequence on incu bation with normal human serum. Complement activation by the peptide w as comparable with that induced by aggregated IgG, complete rgp120, an d the previously described complement-activating gp41-peptide 609-623. Activation occurred via the classical pathway and was abrogated in th e presence of EDTA, Mg2+/EGTA, or C4-deficient human serum. Peptides p artly overlapping the sequence 233-251 activated complement to a lesse r extent. The complement-activating capacity of the gp120 sequence 233 -251 was not restricted to the HIV-1(BRU) isolate, because a peptide f rom the corresponding sequence of the HIV-1(MN) strain was also capabl e of activating complement. An additional strong complement-activating site was identified in the gp120 sequence 321-360 of the HIV-1(MN) st rain. These data indicate that distinct sites in gp120 are able to act ivate human serum complement via the classical pathway in the absence of anti-gp120 and independent of glycosylation. (C) 1996 by The Americ an Society of Hematology.