生物
NS3型
病毒学
解旋酶
登革热病毒
病毒复制
乙酰化
RNA解旋酶A
登革热
黄病毒
聚合酶
寨卡病毒
病毒
核糖核酸
遗传学
丙型肝炎病毒
DNA
基因
作者
Taryn M. Serman,Cindy Chiang,Guanqun Liu,Zuberwasim Sayyad,Shanti Pandey,Meta Volcic,Haejeong Lee,Santoshi Muppala,Dhiraj Acharya,Christopher M. Goins,Shaun R. Stauffer,Konstantin M.J. Sparrer,Michaela U. Gack
标识
DOI:10.1016/j.chom.2023.06.013
摘要
Direct targeting of essential viral enzymes such as proteases, polymerases, and helicases has long been the major focus of antiviral drug design. Although successful for some viral enzymes, targeting viral helicases is notoriously difficult to achieve, demanding alternative strategies. Here, we show that the NS3 helicase of Zika virus (ZIKV) undergoes acetylation in its RNA-binding tunnel. Regulation of the acetylated state of K389 in ZIKV NS3 modulates RNA binding and unwinding and is required for efficient viral replication. NS3 acetylation is mediated by a specific isoform of the host acetyltransferase KAT5 (KAT5γ), which translocates from the nucleus to viral replication complexes upon infection. NS3 acetylation by KAT5γ and its proviral role are also conserved in West Nile virus (WNV), dengue virus (DENV), and yellow fever virus (YFV). Our study provides molecular insight into how a cellular acetyltransferase regulates viral helicase functions, unveiling a previously unknown target for antiviral drug development.
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