FURTHER CHARACTERIZATION OF THE INTERACTION BETWEEN THE C1Q SUBCOMPONENT OF HUMAN C1 AND THE TRANSMEMBRANE ENVELOPE GLYCOPROTEIN GP41 OF HIV-1

Previous studies have provided evidence for activation of the human C1 complex by HIV-1, resulting from direct interaction between C1q and t he external portion of the viral transmembrane envelope protein, rsgp4 1. The present study was undertaken to locate more precisely, with in C1q and rsgp41, the sites involved in the C1/HIV-1 interaction. Using a solid phase binding assay, we showed that I-125-labeled Clq binding to rsgp41 was dose dependent, saturable, and comparable with binding o f C1q to IgG-OVA immune complexes. The globular and, to a lesser exten t, the collagen-like regions of C1q both bound to rsgp41. In contrast, the globular region of C1q inhibited the C1q/rsgp41 interaction, wher eas the collagen-like region of C1q did not. A series of peptides cove ring the putative C1q-binding site on gp41 (positions 590-613 of gp160 ) were synthesized and used as competitors in the C1q-rsgp41-binding a ssay. Peptide 601-613 (GIWGCSGKLICTT) inhibited C1q binding the most e fficiently, with 50% inhibition at a concentration of 100 muM. This pe ptide also inhibited binding of C1q to rsgp36, the protein of HIV-2 ho mologous to rsgp4l. The inhibitory effect of this peptide was dependen t in part on the presence of the S-S bridge normally connecting Cys 60 5 to Cys 611 because reduction of this bond significantly reduced its efficiency. These data suggest that the C1q/HIV-1 interaction involves a site on C1q located within the globular regions, and a major site l ocated within the immunodominant domain of HIV-1, which shares homolog y with the corresponding region of HIV-2.