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 the addition of exogenous human AB+ seronegative complement. The current study was performed to determine whether infectious plasma virus was inactivated by complement. Incubation of plasma virus with AB+-seronegative serum resulted in substantial decreases in infectious titers, demonstrating that infectious plasma virus is susceptible to complement-mediated inactivation. Although complement also induced some lysis of plasma virus samples, virus was neutralized to a significantly higher 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 important 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 bound virus in vivo. Furthermore, plasma virus samples that had less C3 deposited on their surface in vivo had higher infectious titers than samples with a larger fraction with surface C3. These findings suggest that complement can neutralize HIV-1 plasma virus in vivo by coating with complement proteins. This is the first study to provide evidence that coating by complement leads to functional inactivation of a virus in vivo.