Schultz U, Köck J, Schlicht H J, Staeheli P
Department of Virology, Institute for Medical Microbiology and Hygiene, Freiburg, Germany.
Virology. 1995 Oct 1;212(2):641-9. doi: 10.1006/viro.1995.1522.
Although interferon is widely used to treat chronic hepatitis B virus infections, its mode of action against hepadnaviruses is largely unknown. This deficit is due mainly to the lack of suitable model systems. The duck system could not be used because purified duck interferon was not available in sufficient quantities. We have now cloned a DNA fragment that contains an intronless gene for duck interferon. The primary translation product consists of 191 amino acids, the N-terminal 30 residues of which constitute a signal peptide. Mature duck interferon is 50% identical to the recently cloned chicken interferon. Sequence homology to mammalian interferons is marginal, but conservation of four cysteine residues and inducibility by virus indicate a distant relationship between duck interferon and mammalian type I interferons. Purified recombinant duck interferon from Escherichia coli is biologically active: it activates the interferon-inducible Mx gene, prevents cell destruction by cytolytic RNA viruses, and has a strong inhibitory effect on duck hepatitis B virus in cultured primary duck hepatocytes. This new reagent should help to define the interferon-sensitive step of the hepadnavirus life cycle. Furthermore, the duck system can now be used for systematic studies of the in vivo effectiveness of interferon in chronic hepatitis B virus infections.
虽然干扰素被广泛用于治疗慢性乙型肝炎病毒感染，但其针对嗜肝DNA病毒的作用模式在很大程度上尚不清楚。这一缺陷主要是由于缺乏合适的模型系统。由于无法获得足够数量的纯化鸭干扰素，所以不能使用鸭系统。我们现已克隆出一个DNA片段，它包含鸭干扰素的一个无内含子基因。初级翻译产物由191个氨基酸组成，其中N端的30个残基构成一个信号肽。成熟的鸭干扰素与最近克隆的鸡干扰素具有50%的同一性。与哺乳动物干扰素的序列同源性很有限，但四个半胱氨酸残基的保守性以及病毒诱导性表明鸭干扰素与哺乳动物I型干扰素存在远亲关系。从大肠杆菌中纯化的重组鸭干扰素具有生物活性：它能激活干扰素诱导的Mx基因，防止溶细胞性RNA病毒对细胞的破坏，并对培养的原代鸭肝细胞中的鸭乙型肝炎病毒有强烈的抑制作用。这种新试剂应有助于确定嗜肝DNA病毒生命周期中对干扰素敏感的步骤。此外，鸭系统现在可用于对干扰素在慢性乙型肝炎病毒感染中的体内有效性进行系统研究。
