The Nucleolar Phosphoprotein B23 Interacts with Hepatitis Delta Antigens and Modulates the Hepatitis Delta Virus RNA Replication

Wen Hung Huang, Benjamin Y M Yung, Wan Jr Syu, Yan-Hwa Wu Lee*

*此作品的通信作者

研究成果: Article同行評審

79 引文 斯高帕斯(Scopus)

摘要

Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs). The small form of HDAg is required for HDV RNA replication, while the large form of HDAg inhibits the viral replication and is required for virion assembly. In this study, we found that the expression of B23, a nucleolar phosphoprotein involved in disparate functions including nuclear transport, cellular proliferation, and ribosome biogenesis, is up-regulated by these two HDAgs. Using in vivo and in vitro experimental approaches, we have demonstrated that both isoforms of HDAg can interact with B23 and their interaction domains were identified as the NH2-terminal fragment of each molecule encompassing the nuclear localization signal but not the coiled-coil region of HDAg. Sucrose gradient centrifugation analysis indicated that the majority of small HDAg, but a lesser amount of the large HDAg, co-sedimented with B23 and nucleolin in the large nuclear complex. Transient transfection experiments also indicated that introducing exogenous full-length B23, but not a mutated B23 defective in HDAg binding, enhanced HDV RNA replication. All together, our results reveal that HDAg has two distinct effects on nucleolar B23, up-regulation of its gene expression and the complex formation, which in turn regulates HDV RNA replication. Therefore, this work demonstrates the important role of nucleolar protein in regulating the HDV RNA replication through the complex formation with the key positive regulator being small HDAg.

原文English
頁(從 - 到)25166-25175
頁數10
期刊Journal of Biological Chemistry
276
發行號27
DOIs
出版狀態Published - 6 7月 2001

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