Glenn J S, White J M
Departments of Biochemistry, University of California, San Francisco 94143-0450.
J Virol. 1991 May;65(5):2357-61. doi: 10.1128/JVI.65.5.2357-2361.1991.
Infection with hepatitis delta virus (HDV) is an important cause of acute and chronic liver disease and can be rapidly fatal. Sequencing of the HDV RNA genome has revealed variability at the C-terminal end of the delta antigen reading frame. One genome type (termed the S genome) synthesizes a 24-kDa protein thought to be required for genome replication. Another genome type (termed the L genome) extends the reading frame by 19 amino acids as a result of a single base change. Replication of the S and L genomes was studied in cultured fibroblasts. While the S genome efficiently initiated genome replication, the L genome did not. Moreover, in a codelivery experiment, L genome RNA inhibited replication of the S genome. Potent trans inhibition was also observed following cotransfection of the S genome and a plasmid encoding the larger delta antigen. Mutational analysis indicated that the inhibitory activity was not a simple function of the large delta antigen reading frame's extra length. Implications for the viral life cycle, clinical infection, and potential treatment are discussed.
丁型肝炎病毒（HDV）感染是急性和慢性肝病的重要病因，且可能迅速致命。HDV RNA基因组测序揭示了δ抗原阅读框C末端的变异性。一种基因组类型（称为S基因组）合成一种24 kDa的蛋白质，被认为是基因组复制所必需的。另一种基因组类型（称为L基因组）由于单个碱基变化，使阅读框延伸了19个氨基酸。在培养的成纤维细胞中研究了S和L基因组的复制。虽然S基因组有效地启动了基因组复制，但L基因组却不能。此外，在共传递实验中，L基因组RNA抑制了S基因组的复制。在S基因组与编码较大δ抗原的质粒共转染后，也观察到了强烈的反式抑制作用。突变分析表明，抑制活性并非大δ抗原阅读框额外长度的简单函数。文中讨论了其对病毒生命周期、临床感染及潜在治疗的影响。
