Protzer U, Nassal M, Chiang P W, Kirschfink M, Schaller H
Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10818-23. doi: 10.1073/pnas.96.19.10818.
Hepatitis B viruses specifically target the liver, where they efficiently infect quiescent hepatocytes. Here we show that human and avian hepatitis B viruses can be converted into vectors for liver-directed gene transfer. These vectors allow hepatocyte-specific expression of a green fluorescent protein in vitro and in vivo. Moreover, when used to transduce a type I interferon gene, expression of interferon efficiently suppresses wild-type virus replication in the duck model of hepatitis B virus infection. These data suggest local cytokine production after hepatitis-B-virus-mediated gene transfer as a promising concept for the treatment of acquired liver diseases, including chronic hepatitis B.
乙型肝炎病毒特异性靶向肝脏,在那里它们能有效感染静止的肝细胞。我们在此表明,人类和禽类乙型肝炎病毒可被转化为用于肝脏定向基因转移的载体。这些载体在体外和体内均可实现绿色荧光蛋白的肝细胞特异性表达。此外,当用于转导I型干扰素基因时,干扰素的表达能在乙型肝炎病毒感染的鸭模型中有效抑制野生型病毒复制。这些数据表明,乙型肝炎病毒介导的基因转移后产生局部细胞因子是治疗包括慢性乙型肝炎在内的获得性肝脏疾病的一个有前景的概念。