M13 BACTERIOPHAGE DNA INHIBITS DUCK HEPATITIS-B VIRUS DURING ACUTE INFECTION

We investigated effects of various DNAs on duck hepatitis B virus repl ication in vivo. One-day-old ducks were infected intravenously with DH BV. Various DNAs were then injected intravenously, and duck hepatitis B virus levels were followed for up to 20 days after the inoculation. When M13 bacteriophage DNA (M13 DNA), heat-denatured Escherichia coil DNA or Phi X 174 phage DNA was injected intravenously at a dose of 2.4 5 mg/kg body wt daily for 10 days, a significant decrease of serum duc k hepatitis B virus DNA was detected within 10 days. The efficacy was twice that reported with antisense DNA on a weight basis and far more than that reported on a molar basis. M13 DNA was superior, on the basi s of effective dose, to acyclovir as an anti-duck hepatitis B virus ag ent. On treatment with M13 DNA, serum 2-5 A synthetase level was incre ased five to six times, suggesting that the antiviral effect of M13 DN A is at least partly due to induction of endogenous interferon, which in turn induces 2-5 A synthetase. No significant inhibitory effect on replication of duck hepatitis B virus was demonstrated by DNAs obtaine d from herring testes, herring sperm, salmon testes, human placenta or calf thymus. On discontinuation of M13 DNA injection on day 10, duck hepatitis B virus reappeared in the serum at later time points. Digest ion of M13 DNA with S1 nuclease resulted in marked reduction of antivi ral activity. These results show that M13 DNA, not its digested produc t, has potent antiviral activity.