COMPLEMENT CAN NEUTRALIZE HIV-1 PLASMA VIRUS BY A C5-INDEPENDENT MECHANISM

A previous study showed a portion of HIV-1 plasma virus was lysed by t he addition of exogenous human AB(+) seronegative complement. The curr ent study was performed to determine whether infectious plasma virus w as inactivated by complement. Incubation of plasma virus with AB(+)-se ronegative serum resulted in substantial decreases in infectious titer s, demonstrating that infectious plasma virus is susceptible to comple ment-mediated inactivation. Although complement also induced some lysi s of plasma virus samples, virus was neutralized to a significantly hi gher degree, suggesting neutralization did not occur solely by lysis. Additionally C5-deficient complement substantially neutralized virus, indicating coating of virus by early complement components was an impo rtant mechanism of neutralization. A portion of some freshly isolated plasma virus samples bound to complement receptor 2 in the absence of exogenous complement, indicating that early complement components boun d virus in vivo. Furthermore, plasma virus samples that had less C3 de posited on their surface in vivo had higher infectious titers than sam ples with a larger fraction with surface C3. These findings suggest th at complement can neutralize HIV-1 plasma virus in vivo by coating wit h complement proteins. This is the first study to provide evidence tha t coating by complement leads to functional inactivation of a virus in vivo. (C) 1998 Academic Press.