3'-Azido-3'-deoxythymidine-induced reduction in the ability of uninfected CD4-expressing cells to participate in syncytium formation

A cocultivation assay system consisting of uninfected human T cells and cells chronically infected with human immunodeficiency virus type 1 has been used to investigate syncytium formation in short-term assays. Continuous treatment or short-term pretreatment of uninfected CD4-expressing human T-cell lines with 3'-azido-3'-deoxythymidine (AZT) reduces the ability of these cells to participate in syncytium formation when mixed with chronically infected cells. The effect of AZT on syncytium formation is observed both as a reduction in the number of syncytia and as a reduction in the size of the syncytia that are detected. This syncytium-reducing effect of AZT is dose and time dependent and does not result from a modulation of CD4 antigen expression on the cell surface of uninfected, treated cells. Maximum syncytium reduction is observed with the continuous presence of AZT; however, pretreatment for times as short as 15 min results in a significant reduction in syncytium formation. Since reverse transcription is not required for efficient syncytium formation, the syncytium-reducing effect of AZT on uninfected human cells may represent an antiviral property of AZT with important therapeutic potential.