Abstract |
We report that 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine inhibit retroviral DNA synthesis and mRNA expression in T cells exposed to the virus that causes acquired immunodeficiency syndrome, and afford such cells long-term protection in vitro under conditions of substantial viral excess. Both 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine appear to completely block reverse transcription from viral RNA to viral DNA. Viral mRNA expression is also not detected in cells protected by the drugs throughout 30 days of culture following exposure to the virus. Purine and pyrimidine analogues as 2',3'-dideoxynucleoside-5'-triphosphate serve as substrates for the human T-lymphotropic virus type III/lymphadenopathy-associated virus reverse transcriptase to elongate a DNA chain by one residue, after which the chain is terminated. Cloned normal helper/inducer T cells exposed to a cytopathic dose of the virus, but protected by the drugs, respond normally to specific antigen in vitro. These results suggest that the drugs could be promising agents for further studies in the experimental treatment of patients infected with retroviruses.
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Authors | H Mitsuya, R F Jarrett, M Matsukura, F Di Marzo Veronese, A L DeVico, M G Sarngadharan, D G Johns, M S Reitz, S Broder |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 84
Issue 7
Pg. 2033-7
(Apr 1987)
ISSN: 0027-8424 [Print] United States |
PMID | 2436223
(Publication Type: Journal Article)
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Chemical References |
- Antiviral Agents
- Deoxyadenosines
- RNA, Messenger
- Deoxycytidine
- Dideoxyadenosine
- Zalcitabine
- RNA-Directed DNA Polymerase
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Topics |
- Antiviral Agents
- Base Sequence
- Cell Line
- DNA Replication
(drug effects)
- Deoxyadenosines
(analogs & derivatives, pharmacology)
- Deoxycytidine
(analogs & derivatives, pharmacology)
- Dideoxyadenosine
- HIV
(drug effects, genetics)
- Humans
- RNA, Messenger
(drug effects, genetics)
- RNA-Directed DNA Polymerase
(metabolism)
- T-Lymphocytes
(drug effects)
- Transcription, Genetic
(drug effects)
- Zalcitabine
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