hnRNPA1 impedes snakehead vesiculovirus replication via competitively disrupting viral phosphoprotein-nucleoprotein interaction and degrading viral phosphoprotein.

hnRNPA1 impedes snakehead vesiculovirus replication via competitively disrupting viral phosphoprotein-nucleoprotein interaction and degrading viral phosphoprotein.
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DOI:
10.1080/21505594.2023.2196847
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发表时间:
2023-12
期刊:
影响因子:
5.2
通讯作者:
Tu, Jiagang
Tu, Jiagang
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, An-Qi;Qin, Xiangmou;Wu, Hui;Feng, Hao;Zhang, Yong-An;Tu, Jiagang

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异质核核糖核蛋白 A1 (hnRNPA1) 在调节许多病毒的复制中发挥着重要作用。然而,hnRNPA1 是否以及如何调节鱼类病毒复制仍不清楚。本研究筛选了 12 个 hnRNP 对蛇头水泡病毒 (SHVV) 复制的影响。三个 hnRNP,其中之一是 hnRNPA1,被鉴定为抗 SHVV 因子。进一步验证表明,hnRNPA1的敲除促进SHVV复制,而hnRNPA1的过表达则抑制SHVV复制。 SHVV感染降低hnRNPA1的表达水平并诱导hnRNPA1的核质穿梭。此外,我们发现 hnRNPA1 通过其富含甘氨酸的结构域与病毒磷蛋白(P)相互作用,但不与病毒核蛋白(N)或大蛋白(L)相互作用。 hnRNPA1-P 相互作用竞争性地破坏了病毒 P-N 相互作用。此外,我们发现 hnRNPA1 的过度表达增强了 P 蛋白的多泛素化,并通过蛋白酶体和溶酶体途径降解它。这项研究将有助于了解 hnRNPA1 在单链负义 RNA 病毒复制中的功能,并提供针对鱼类弹状病毒的新型抗病毒靶点。
Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays an important role in regulating the replication of many viruses. However, it remains elusive whether and how hnRNPA1 regulates fish virus replication. In this study, the effects of twelve hnRNPs on the replication of snakehead vesiculovirus (SHVV) were screened. Three hnRNPs, one of which was hnRNPA1, were identified as anti-SHVV factors. Further verification showed that knockdown of hnRNPA1 promoted, while overexpression of hnRNPA1 inhibited, SHVV replication. SHVV infection reduced the expression level of hnRNPA1 and induced the nucleocytoplasmic shuttling of hnRNPA1. Besides, we found that hnRNPA1 interacted with the viral phosphoprotein (P) via its glycine-rich domain, but not with the viral nucleoprotein (N) or large protein (L). The hnRNPA1-P interaction competitively disrupted the viral P-N interaction. Moreover, we found that overexpression of hnRNPA1 enhanced the polyubiquitination of the P protein and degraded it through proteasomal and lysosomal pathways. This study will help understanding the function of hnRNPA1 in the replication of single-stranded negative-sense RNA viruses and providing a novel antiviral target against fish rhabdoviruses.
DOI: 10.1080/21505594.2021.2014681
发表时间: 2021-12
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影响因子: 5.2
作者:
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