TRANSDOMINANT INHIBITION OF HUMAN HEPATITIS-DELTA VIRUS GENOME REPLICATION

被引:92
作者
GLENN, JS
WHITE, JM
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT PHARMACOL, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1128/JVI.65.5.2357-2361.1991
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:2357 / 2361
页数:5
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