错位双链RNA,丙氧鸟苷和原核细胞DNA促旋酶B对鸭乙肝病毒的抑制作用

人工合成错位双链ＲＮＡ（ａｍｐｌｉｇｅｎ）是一种已知的干扰素诱导剂。单独和／或与其它抗病毒药物联合使用治疗鸭乙型肝炎病毒（ＤＨＢＶ）阳性鸭。这些药物包括丙氧鸟苷（ｇａｎｃｉｃｌｏｖｉｒ）和原核细胞ＤＮＡ促旋酶Ｂ抑制物（ｃｏｕｍｅｒｍｙｃｉｎＡｌ）。单独和／或联合该两种药物时，对鸭血清和肝组织内ＤＨＢＶ均有抑制作用，但以三种药物联合时抑制效果最好。上述下种方案治疗结束后肝内松弛环状ＤＮＡ（ＲＣ）和超螺旋ＤＮＡ（ＳＣ）持续存在，而且不能消除血中鸭乙肝表面抗原（ＤＨＢｓＡｇ）。对治疗的大多数鸭血清干扰素，测定结果表明，ａｍｐｌｉｇｅｎ能诱生鸭干扰素，但其出现时间与抗病毒效果产生没有平行关系。本研究为人慢性乙型肝炎治疗合理使用抗病毒药物和免疫诱导剂提供了参考。

The Use of Ampligen Alone and in Combination with Ganciclovirand Coumermycin A1 for the Treatment of Ducks Congenitally Infectedwith Duck Hepatitis B Virus

mpligen,a known immunomodulator and interferon inducer.was used alone and in conibination with other antiviral agents to treat ducks congenitally infected with duck hepatitis B virus.Theseantiviral agents included the conventional nucleotide analogue gunciclovir and the prokaryotic DNA gyrase B inhibitor coumermycin A1.When use alone,ampligen decreased the amount of serum and liverviral DNA,but had no effeet on circulating duck hepatitis B surface antigen (DHBsAg).In combination with sanciclovir,the antiviral effect appeared at least additive with a greater inhibition of vicalDNA replication within the liver.The conibination of ampligen with coutiiermycin A1 also resulted ininhibition of viral replication but to a lesser extent than ampligen alone.When all three agents wereused tapether,viral DNA replication was inhibited to the greatest extent but as with previous treatmentregimes,DHRsAg levels remained unchanged.At the end of the treatnient period for all resinies,analysis of viral DNA forms in the liver showed that the viral relaxed circular and supercoiled DNA formshad persisted.Within one week of cessation of therapy, viral replication had often returned to pre-treatment levels.Interferon-like activity was detected in the sera of the majcarity or the treated ducksduring the amplisen therapy,but no clear relationship between the presence uf interferon and antivicaleffect could be established.These othervations in the duck hepatitis B model may provide a rational basis for the use of combinations of antiviral and inimunomedulatory regimes for the management ofchronic hepotitis B infection in man.