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In vitro inhibition of hepatitis B virus replication by 2',3'-dideoxyguanosine, 2',3'-dideoxyinosine, and 3'-azido-2',3'-dideoxythymidine in 2.2.15 (PR) cells. 1991

S Aoki-Sei, and M C O'Brien, and H Ford, and H Fujii, and D A Gilbert, and D A Cooney, and D G Johns, and S Broder, and H Mitsuya
Clinical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Hep G2-derived hepatoblastoma cells (2.2.15), which actively produce hepatitis B virus (HBV), were cultured in the presence of 2',3'-dideoxyguanosine (ddG), 2',3'-dideoxyinosine, or 3'-azido-2',3'-dideoxythymidine (AZT). ddG was the most potent agent. It diminished viral replication by up to 95%, as assessed by the amount of episomal HBV DNA, without impairing cellular growth. AZT was the least effective against HBV. Northern blot analysis revealed no apparent difference in the pregenomic viral RNA profile, suggesting that these dideoxynucleosides suppress reverse transcription in the replicative cycle of HBV. The effect of varying the time of drug exposure showed that these agents can suppress HBV replication even when added late in culture. HBV replication in another 2.2.15 cell population of the same lineage was affected by ddG differently, which may enable the investigation of phenotypic or genetic alterations during culture. The present data suggest that some 2',3'-dideoxynucleosides can exert a potent antiviral activity against HBV in vitro, at least under certain circumstances, although the data do not prove that any of these agents have utility in patients with hepatitis.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015139 Blotting, Southern A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES. Southern Blotting,Blot, Southern,Southern Blot
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U

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