EFFICIENT DESTRUCTION OF HUMAN-IMMUNODEFICIENCY-VIRUS IN HUMAN SERUM BY INHIBITING THE PROTECTIVE ACTION OF COMPLEMENT FACTOR-H AND DECAY-ACCELERATING FACTOR (DAF, CD55)

Activation of the human complement system leads to complement depositi on on human immunodeficiency virus (HIV) and HIV-infected cells withou t causing efficient complement-mediated lysis. Even in the presence of HIV-specific antibodies, only a few particles are destroyed, demonstr ating that HIV is intrinsically resistant to human complement. Here we report that, in addition to decay accelerating factor (DAF) being par tially responsible, human complement factor H (CFH), a humoral negativ e regulator of complement activation, is most critical for this resist ance. In the presence of HIV-specific antibodies, sera devoid of CFH ( total genetic deficiency or normal human serum depleted of CFH by affi nity chromatography) lysed free virus and HIV-infected but not uninfec ted cells. In the presence of CFH, lysis of HIV was only obtained when binding of CFH to gp41 was inhibited by a monoclonal antibody against a main CFH-binding site in gp41. Since CFH is an abundant protein in serum, and high local concentration of CFH can be obtained at the surf ace of HIV as the result of specific interactions of CFH with the HIV envelope, it is proposed that the resistance of HIV and HIV-infected c ells against complement-mediated lysis in vivo is dependent on DAF and CFH and can be overcome by suppressing this protection. Neutralizatio n of HIV may be achieved by antibodies against DAF and, more important ly, antibodies against CFH-binding sites on HIV envelope proteins.