Inhibition of murine AIDS (MAIDS) development in C57BL/6J mice by tyrphostin AG-1387

We previously showed that certain tyrphostin derivatives, known as protein tyrosine kinase inhibitors, also act as topoisomerase I-specific antagonist s and inhibit Moloney murine leukemia virus replication in vitro in acutely and chronically infected cells. However, an accurate portrayal of retrovir al-induced disease cannot rely exclusively on extrapolations from in vitro data. Therefore, experiments with animal models are essential for evaluatin g the efficacy of a specific drug in vivo. In this study, we examined the e ffect of tyrphostin AG-1387 on murine AIDS (MAIDS) development in C57BL/6J mice injected with the LP-BM5 virus mixture. A single dose of tyrphostin, a dministered together with or 24 h post virus inoculation, decreased the dev elopment of MAIDS symptoms as measured by spleen and lymph node weight, the T-cell response to concanavalin A (con A), and spleen architecture, Furthe rmore, weekly treatment with tyrphostins totally abolished MAIDS symptoms a nd prevented the viral infection of the spleen cells as measured by the abs ence of viral RNA and the restoration of T-cell function in these spleens. These results implicate that prolonged treatment with tyrphostins is needed for the prevention of MAIDS development in infected mice and suggest that it may be applied as a legitimate remedy for the treatment of retroviral-in duced diseases, (C) 2000 Academic Press.