3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.
The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.
Mitsuya
H
H
Weinhold
K J
KJ
Furman
P A
PA
St Clair
M H
MH
Lehrman
S N
SN
Gallo
R C
RC
Bolognesi
D
D
Barry
D W
DW
Broder
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000998:Antiviral Agents / Q000494:pharmacology*; D017977:Deltaretrovirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015683:Gene Products, gag; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015215:Zidovudine
D000998:Antiviral Agents; D015683:Gene Products, gag; D012191:Retroviridae Proteins; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D013936:Thymidine