Efficacy of 3 '-azido 3 ' deoxythymidine (AZT) in preventing HTLV-1 transmission to human cord blood mononuclear cells

The present study investigated the effect of 3'-azido 3'deoxythymidine (AZT ) treatment on in vitro infection of human cord blood mononuclear cells (CB MCs) exposed to HTLV-1 by cocultivation with the MT-2 cell line. Cultures o f CBMCs were grown in IL-2 and were either left untreated or were treated w ith concentrations of AZT ranging from 0.0078 to 32 muM. HTLV-1-infected cu ltures were monitored at different times of culture by evaluating prolifera tion activity, cell growth and the presence and expression of HTLV-1 genes. Results showed that untreated cultures infected with HTLV-1 were able to g row for several weeks, while those treated with AZT at 0.03 muM or higher c oncentrations were limited in their growth capacity. Moreover, the addition of AZT at the moment of infection significantly inhibited cell proliferati on in a dose-dependent fashion. In the presence of AZT, detection of provir al DNA and, more remarkably, viral RNA expression were clearly reduced. In addition, treatment with AZT resulted in a noticeable decrease in Tax prote in expression. Using treatment with relatively low doses of AZT, effective in exerting an antiviral action, cytotoxicity on CBMCs was not observed, wh ereas higher doses induced apoptosis in uninfected CBMCs. These data show t hat CBMCs are protected by AZT against HTLV-1 transmission even at low, non -toxic doses. (C) 2001 Elsevier Science B.V. All rights reserved.