Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection

Objective: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-AD) of HIV infection which may play a significant role in the progression of HIV-disease. Methods: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1(IIIB) and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. Results: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. Conclusion: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.