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 (CBMCs) exposed to HTLV-1 by cocultivation with the MT-2 cell line. Cultures of CBMCs were grown in IL-2 and were either left untreated or were treated with concentrations of AZT ranging from 0.0078 to 32 microM. HTLV-1-infected cultures were monitored at different times of culture by evaluating proliferation activity, cell growth and the presence and expression of HTLV-1 genes. Results showed that untreated cultures infected with HTLV-1 were able to grow for several weeks, while those treated with AZT at 0.03 microM or higher concentrations were limited in their growth capacity. Moreover, the addition of AZT at the moment of infection significantly inhibited cell proliferation in a dose-dependent fashion. In the presence of AZT, detection of proviral DNA and, more remarkably, viral RNA expression were clearly reduced. In addition, treatment with AZT resulted in a noticeable decrease in Tax protein expression. Using treatment with relatively low doses of AZT, effective in exerting an antiviral action, cytotoxicity on CBMCs was not observed, whereas higher doses induced apoptosis in uninfected CBMCs. These data show that CBMCs are protected by AZT against HTLV-1 transmission even at low, non-toxic doses.
Zhang
J
J
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Balestrieri
E
E
Grelli
S
S
Matteucci
C
C
Pagnini
V
V
D'Agostini
C
C
Mastino
A
A
Macchi
B
B
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood; D016356:Gene Products, tax / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000821:virology*; D011533:Proviruses / Q000302:isolation & purification; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D004279:DNA, Viral; D016356:Gene Products, tax; D012367:RNA, Viral; D015215:Zidovudine