Rapid screening method with a cell multisizer for inhibitors of human immunodeficiency virus-induced cell fusion in vitro.

Abstract

Cocultivation of MOLT-4 and MOLT-4/HIVHTLV-IIIB cells induces syncytium formation very efficiently and is an appropriate model for evaluation of various substances which might inhibit human immunodeficiency virus (HIV)-induced multinucleated giant cell formation in vitro. We attempted here to quantify the grade of the syncytium formation by using a cell multisizer. The size distribution pattern of the cocultivated cells in the presence of glycyrrhizin sulfate, polysaccharide Krestin, dextran sulfate, ribofuranan sulfate, and lentinan sulfate was indistinguishable from that of cocultured cells grown in the absence of inhibitors. However, the pattern of cocultured cells without an inhibitor was quite different from that of MOLT-4 or MOLT-4/HIVHTLV-IIIB cells alone. Moreover, the size distribution pattern of cocultured cells after treatment with two nucleoside analogs, 3'-azido-2',3'-dideoxythymidine and 2',3'-didehydro-2',3'-dideoxythymidine, which were known to inhibit cell-free but not cell-to-cell infection, was similar to that of cocultured cells without an inhibitor. These data are well correlated with the fusion index which was reported previously. Application of the cell multisizer is very quantitative for evaluating the syncytium formation induced by HIV and providing a simple and rapid screening for anti-HIV substances, especially for virus-induced cell fusion.