Inhibition of human immunodeficiency virus type-1-induced syncytium formation and cytopathicity by complestatin.

Complestatin, an anti-complement agent, was shown to be a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) infection in vitro. It inhibited HIV-1-induced cytopathicity and HIV-1 antigen expression in MT-4 cells; the 50% effective doses for these effects were 2.2 and 1.5 μg/ml, respectively. No toxicity for MT-4 cells was observed at concentrations up to 400 μg/ml. In addition, the agent inhibited the focus formation in HT4-6C cells (CD4-positive HeLa cells); the concentration for 50% focus reduction was 0.9 μg/ml. HIV-1-induced cell fusion in cocultures of MOLT-4 cells and MOLT-4HTLV-IIIB were also blocked by complestatin (the concentration for 50% cell fusion inhibition, 0.9 μg/ml). Complestatin had no ability to inhibit HIV-1 reverse transcriptase activity. When MT-4 cells were pretreated with complestatin for 2 hrs prior to the exposure to HIV-1, the HIV-1-induced cytopathicity was markedly inhibited, while pretreatment of HIV-1 with the agent did not affect the infection. These results suggest that complestatin primarily interacts with cells and inhibits viral adsorption to the cell surface as well as adsorption of infected cells to adjacent cells.