pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
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DOI：
10.7554/elife.08939
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发表时间：
2015-10-29
期刊：
影响因子：
7.7
通讯作者：
Nagata, Kyosuke
中科院分区：
文献类型：
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作者：
Sugiyama, Kenji;Kawaguchi, Atsushi;Nagata, Kyosuke
流感病毒基因组RNA（vRNA）的复制由病毒RNA依赖性RNA聚合酶（vRdRP）催化。首先从vRNA复制互补RNA（cRNA），然后从cRNA扩增子代vRNA。虽然vRdRP和病毒RNA是最低要求，但仅使用这些病毒因子无法复制有效的无细胞复制。使用生物化学互补测定系统，我们在未感染细胞的核提取物中发现了一种新的活性，命名为IREF-2，其允许从cRNA模板稳健地合成未引发的vRNA。IREF-2显示由宿主衍生的蛋白质pp 32和APRIL组成。IREF-2与游离形式的vRdRP相互作用，并优先上调vRNA合成而不是cRNA合成。敲除实验表明IREF-2参与体内病毒复制。在这些结果和以前的研究的基础上，IREF-2在vRNA复制的起始过程中的合理作用进行了讨论。
Replication of influenza viral genomic RNA (vRNA) is catalyzed by viral RNA-dependent RNA polymerase (vRdRP). Complementary RNA (cRNA) is first copied from vRNA, and progeny vRNAs are then amplified from the cRNA. Although vRdRP and viral RNA are minimal requirements, efficient cell-free replication could not be reproduced using only these viral factors. Using a biochemical complementation assay system, we found a novel activity in the nuclear extracts of uninfected cells, designated IREF-2, that allows robust unprimed vRNA synthesis from a cRNA template. IREF-2 was shown to consist of host-derived proteins, pp32 and APRIL. IREF-2 interacts with a free form of vRdRP and preferentially upregulates vRNA synthesis rather than cRNA synthesis. Knockdown experiments indicated that IREF-2 is involved in in vivo viral replication. On the basis of these results and those of previous studies, a plausible role(s) for IREF-2 during the initiation processes of vRNA replication is discussed.