NOVEL ASSAY SYSTEM FAVORABLE FOR THE STUDY OF CELL-TO-CELL TRANSMISSION OF HIV-1 AND ITS APPLICATION TO THE EVALUATION OF ANTI-HIV DRUGS

The cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1) was studied using MOLT-4 cells chronically infected with a variant strain of HIV-1(SF-2) (MOLT-4/HIV-1(SF-2H)) and CD4+ human lymphoid MT-4 cells. MOLT-4/HIV-1(SF-2H) cells produced less than 1 TCID50 infectious particles per 10(5) cells per day as determined by the cytopathogenicity in MT-4 cells. However, the expression of envelope glycoproteins gp120 and gp41 on the MOLT-4/HIV-1(SF-2H) cell membrane was satisfactory for syncytium formation with the uninfected MOLT-4 cells. When MOLT-4/HIV-1(SF-2H) and MT-4 cells were co-cultured, severe cytopathogenicity was observed in MT-4 cells without being accompanied by the formation of multi-nucleated cells. Thus, the system consisting of MOLT-4/HIV-1(SF-2H) and MT-4 cells is convenient for exclusive study of the mechanism of cell-to-cell transmission of HIV-1. Using various compounds, it was confirmed that cell-to-cell transmission required both gp120/gp41-CD4 binding and de novo DNA synthesis.