Casey J L, Gerin J L
Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852, USA.
J Virol. 1995 Dec;69(12):7593-600. doi: 10.1128/JVI.69.12.7593-7600.1995.
RNA editing plays a central role in the life cycle of hepatitis D virus (HDV), a subviral human pathogen. Previous studies (J.L. Casey, K.F. Bergmann, T.L. Brown, and J.L. Gerin, Proc. Natl. Acad. Sci USA 89:7149-7153, 1992; H. Zheng, T.-B. Fu, D. Lazinski, and J. Taylor, J. Virol. 66:4693-4697, 1992) had concluded that the genomic RNA of HDV was the target for RNA editing and that the editing reaction was a conversion of U to C. However, we show here that the antigenomic RNA of HDV is in fact the target for HDV RNA editing, which is therefore a conversion of A to G. This result is verified by using an assay specific for editing on the antigenomic RNA and by analyzing the editing of site-directed mutant RNAs in transfected cells and in cell extracts. Because editing occurs in the absence of viral antigens and the specificity for the HDV editing target site is present even in extracts from Drosophila cells, it is likely that HDV RNA is edited by one or more cellular factors that are conserved among higher eukaryotes. These results raise the likelihood that double-stranded RNA adenosine deaminase specifically edits HDV antigenomic RNA.
RNA编辑在丁型肝炎病毒（HDV，一种亚病毒人类病原体）的生命周期中起着核心作用。先前的研究（J.L.凯西、K.F.伯格曼、T.L.布朗和J.L.格林，《美国国家科学院院刊》89:7149 - 7153，1992；H.郑、T.-B.傅、D.拉津斯基和J.泰勒，《病毒学杂志》66:4693 - 4697，1992）得出结论，HDV的基因组RNA是RNA编辑的靶标，并且编辑反应是U向C的转变。然而，我们在此表明，HDV的反基因组RNA实际上是HDV RNA编辑的靶标，因此编辑反应是A向G的转变。通过使用针对反基因组RNA编辑的特异性检测方法，以及分析转染细胞和细胞提取物中定点突变RNA的编辑情况，验证了这一结果。由于编辑在没有病毒抗原的情况下发生，并且即使在果蝇细胞提取物中也存在对HDV编辑靶位点的特异性，所以HDV RNA很可能是由高等真核生物中保守的一种或多种细胞因子进行编辑的。这些结果增加了双链RNA腺苷脱氨酶特异性编辑HDV反基因组RNA的可能性。
