TY - JOUR
T1 - Inhibition of murine AIDS (MAIDS) development in C57BL/6J mice by tyrphostin AG-1387
AU - Sklan, Ella H.
AU - Gazit, Aviv
AU - Priel, Esther
N1 - Funding Information:
This work was supported by the Joan Baker and Rosalind Henwood Fund and partially by a grant received from the Israeli Ministry of Health. We thank Prof. Asher Meshorer from the Weizmann Institute of Science (Rehovot, Israel) for the histopathologic examinations.
PY - 2000/12/5
Y1 - 2000/12/5
N2 - We previously showed that certain tyrphostin derivatives, known as protein tyrosine kinase inhibitors, also act as topoisomerase I-specific antagonists and inhibit Moloney murine leukemia virus replication in vitro in acutely and chronically infected cells. However, an accurate portrayal of retroviral-induced disease cannot rely exclusively on extrapolations from in vitro data. Therefore, experiments with animal models are essential for evaluating the efficacy of a specific drug in vivo. In this study, we examined the effect 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, administered together with or 24 h post virus inoculation, decreased the development of MAIDS symptoms as measured by spleen and lymph node weight, the T-cell response to concanavalin A (con A), and spleen architecture. Furthermore, weekly treatment with tyrphostins totally abolished MAIDS symptoms and prevented the viral infection of the spleen cells as measured by the absence 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-induced diseases. (C) 2000 Academic Press.
AB - We previously showed that certain tyrphostin derivatives, known as protein tyrosine kinase inhibitors, also act as topoisomerase I-specific antagonists and inhibit Moloney murine leukemia virus replication in vitro in acutely and chronically infected cells. However, an accurate portrayal of retroviral-induced disease cannot rely exclusively on extrapolations from in vitro data. Therefore, experiments with animal models are essential for evaluating the efficacy of a specific drug in vivo. In this study, we examined the effect 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, administered together with or 24 h post virus inoculation, decreased the development of MAIDS symptoms as measured by spleen and lymph node weight, the T-cell response to concanavalin A (con A), and spleen architecture. Furthermore, weekly treatment with tyrphostins totally abolished MAIDS symptoms and prevented the viral infection of the spleen cells as measured by the absence 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-induced diseases. (C) 2000 Academic Press.
UR - http://www.scopus.com/inward/record.url?scp=0034610246&partnerID=8YFLogxK
U2 - 10.1006/viro.2000.0642
DO - 10.1006/viro.2000.0642
M3 - Article
AN - SCOPUS:0034610246
SN - 0042-6822
VL - 278
SP - 95
EP - 102
JO - Virology
JF - Virology
IS - 1
ER -
