Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase.
The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus. Nine ducks were given 11 mg/m2 of dideoxycytidine intravenously every 6 h, and 7 ducks received no treatment. Serum duck hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity decreased in every duck treated with dideoxycytidine. The mean inhibition of deoxyribonucleic acid polymerase and duck hepatitis B virus deoxyribonucleic acid on the third day of treatment measured 64% (p less than 0.01) and 73% (p less than 0.01), respectively. The inhibition of deoxyribonucleic acid polymerase persisted after treatment was stopped, and 4 ducks continued to show greater than 50% inhibition 12 days after stopping treatment. Duck hepatitis B virus deoxyribonucleic acid, which was measured in total cellular deoxyribonucleic acid extracted from liver biopsy specimens obtained before and on the last day of treatment with dideoxycytidine, showed an average inhibition of 96% in 3 ducks treated with dideoxycytidine, but showed no decrease in the remaining 5 ducks. Thus, dideoxycytidine has potent antiviral activity against duck hepatitis B virus and warrants further evaluation as an antiviral agent in the treatment of chronic hepatitis B virus infection in humans.
Kassianides
C
C
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Hoofnagle
J H
JH
Miller
R H
RH
Doo
E
E
Ford
H
H
Broder
S
S
Mitsuya
H
H
D000818:Animals; D004279:DNA, Viral / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000032:analysis; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000502:physiology; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy*; D011201:Poultry Diseases / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000494:pharmacology / Q000627:therapeutic use*
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine; D004259:DNA-Directed DNA Polymerase