Iizuka A, Watanabe T, Kubo T, Yamamoto M, Ogawa K, Ohkuma T, Kaji A
Research Institute for Molecular Genetics, Tsumura & Co., Ibaraki, Japan.
Hepatology. 1994 May;19(5):1079-87.
We investigated effects of various DNAs on duck hepatitis B virus replication in vivo. One-day-old ducks were infected intravenously with DHBV. 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 coli DNA or phi X 174 phage DNA was injected intravenously at a dose of 2.45 mg/kg body wt daily for 10 days, a significant decrease of serum duck 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 basis of effective dose, to acyclovir as an anti-duck hepatitis B virus agent. On treatment with M13 DNA, serum 2-5 A synthetase level was increased five to six times, suggesting that the antiviral effect of M13 DNA 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 obtained 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. Digestion of M13 DNA with S1 nuclease resulted in marked reduction of antiviral activity. These results show that M13 DNA, not its digested product, has potent antiviral activity.
我们研究了各种DNA对鸭乙型肝炎病毒体内复制的影响。将1日龄雏鸭静脉注射感染鸭乙型肝炎病毒（DHBV）。然后静脉注射各种DNA，并在接种后长达20天内跟踪鸭乙型肝炎病毒水平。当以2.45mg/kg体重的剂量每日静脉注射M13噬菌体DNA（M13 DNA）、热变性大肠杆菌DNA或φX174噬菌体DNA，持续10天时，在10天内检测到血清鸭乙型肝炎病毒DNA显著下降。按重量计算，其疗效是反义DNA报道疗效的两倍，按摩尔计算则远高于报道疗效。基于有效剂量，M13 DNA作为抗鸭乙型肝炎病毒药物优于阿昔洛韦。用M13 DNA治疗后，血清2-5A合成酶水平增加了五到六倍，这表明M13 DNA的抗病毒作用至少部分归因于内源性干扰素的诱导，而内源性干扰素又诱导2-5A合成酶。从鲱鱼睾丸、鲱鱼精子、鲑鱼睾丸、人胎盘或小牛胸腺获得的DNA对鸭乙型肝炎病毒复制未显示出显著抑制作用。在第10天停止注射M13 DNA后，鸭乙型肝炎病毒在血清中于随后的时间点再次出现。用S1核酸酶消化M13 DNA导致抗病毒活性显著降低。这些结果表明，具有有效抗病毒活性的是M13 DNA，而非其消化产物。
