ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites

ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites
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DOI:
10.1038/emboj.2011.429
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发表时间:
2012-02-01
期刊:
影响因子:
11.4
通讯作者:
Taniguchi, Koki
Taniguchi, Koki
中科院分区:
生物学1区
文献类型:
--
作者:
Sasaki, Jun;Ishikawa, Kumiko;Taniguchi, Koki

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磷脂酰肌醇4-激酶III β(PI 4KB)是肠道病毒(属于小核糖核酸病毒科的小型无包膜病毒)基因组RNA复制所需的宿主因子。在这里,我们证明了PI 4KB也是另一种小核糖核酸病毒,爱知病毒(AiV)的基因组复制所必需的,但被招募到基因组复制位点的策略与肠道病毒所使用的不同。AiV非结构蛋白2B、2BC、2C、3A和3AB与高尔基体蛋白ACBD 3相互作用。此外,我们确定了以前未知的ACBD 3和PI 4KB之间的相互作用,这提供了一种新的方式高尔基体募集PI 4KB。ACBD 3或PI 4KB的敲低抑制AIV RNA复制。病毒蛋白ACBD 3、PI 4KB和磷脂酰肌醇-4-磷酸(PI 4P)定位于病毒RNA复制位点。与肠道病毒感染相比,AIV复制和PI 4KB向RNA复制位点的募集不受布雷菲德菌素A的影响。这些结果表明,病毒蛋白/ACBD 3/PI 4KB复合物形成以在AiV RNA复制位点合成PI 4P,并且在病毒RNA复制中起重要作用。EMBO期刊(2012)31,754-766。doi:10.1038/daj.2011.429; 2011年11月29日在线发布
Phosphatidylinositol 4-kinase III beta (PI4KB) is a host factor required for genome RNA replication of enteroviruses, small non-enveloped viruses belonging to the family Picornaviridae. Here, we demonstrated that PI4KB is also essential for genome replication of another picornavirus, Aichi virus (AiV), but is recruited to the genome replication sites by a different strategy from that utilized by enteroviruses. AiV non-structural proteins, 2B, 2BC, 2C, 3A, and 3AB, interacted with a Golgi protein, acylcoenzyme A binding domain containing 3 (ACBD3). Furthermore, we identified previously unknown interaction between ACBD3 and PI4KB, which provides a novel manner of Golgi recruitment of PI4KB. Knockdown of ACBD3 or PI4KB suppressed AiV RNA replication. The viral proteins, ACBD3, PI4KB, and phophatidylinositol-4-phosphate (PI4P) localized to the viral RNA replication sites. AiV replication and recruitment of PI4KB to the RNA replication sites were not affected by brefeldin A, in contrast to those in enterovirus infection. These results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication. The EMBO Journal (2012) 31, 754-766. doi: 10.1038/emboj.2011.429; Published online 29 November 2011