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.
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.
Aoki-Sei
S
S
Clinical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
O'Brien
M C
MC
Ford
H
H
Fujii
H
H
Gilbert
D A
DA
Cooney
D A
DA
Johns
D G
DG
Broder
S
S
Mitsuya
H
H
D015139:Blotting, Southern; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D016049:Didanosine / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D004279:DNA, Viral; D015224:Dideoxynucleosides; D012367:RNA, Viral; D015215:Zidovudine; C050220:2',3'-dideoxyguanosine; D016049:Didanosine