Characterization of the antiviral effects of 2' carbodeoxyguanosine in ducks chronically infected with duck hepatitis B virus.
This study was carried out to evaluate benefits and limitations of long-term therapy of hepatitis B virus infections with a nucleoside analog inhibitor of virus replication. The model we used was the domestic duck chronically infected with duck hepatitis B virus by in ovo infection. 2' Carbodeoxyguanosine was used as an inhibitor of viral DNA synthesis. In all animals examined there was a reduction in virus production during therapy. A dose of 2' carbodeoxyguanosine of 10 micrograms/kg every other day reduced the number of infected hepatocytes from greater than 95% to 25% to 50% in less than 3 mo, whereas a 10-fold higher dose produced a decline to less than 10%. Histological evaluation revealed mild to moderate liver injury in ducks receiving the higher dose of 2' carbodeoxyguanosine, suggesting that disappearance of infected hepatocytes may have been accelerated by a toxic effect of the drug. Drug treatment did not completely eliminate duck hepatitis B virus from any duck, and replication was restored in all hepatocytes within a few weeks to several months after antiviral therapy was terminated. Our results suggest that elimination of a chronic infection with a single inhibitor of replication may be difficult in a host that lacks an antiviral immune response capable of eliminating at least a portion of the infected hepatocytes and of ultimately producing antibodies capable of neutralizing residual virus.
Mason
W S
WS
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Cullen
J
J
Saputelli
J
J
Wu
T T
TT
Liu
C
C
London
W T
WT
Lustbader
E
E
Schaffer
P
P
O'Connell
A P
AP
Fourel
I
I
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D015139:Blotting, Southern; D002478:Cells, Cultured; D002908:Chronic Disease; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004372:Ducks; D018347:Hepadnaviridae Infections / Q000188:drug therapy*; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D014766:Viremia / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; C061610:2-amino-1,9-dihydro-9-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-6H-purine-6-one; D003849:Deoxyguanosine