Cell apoptosis regulated by interaction between viral gene alpha 3 and host heterogeneous nuclear ribonucleoprotein K facilitates bovine ephemeral fever virus replication
Cell apoptosis regulated by interaction between viral gene alpha 3 and host heterogeneous nuclear ribonucleoprotein K facilitates bovine ephemeral fever virus replication
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病毒基因α3与宿主相互作用调节细胞凋亡
DOI：
10.1016/j.vetmic.2019.108510
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Wang, Hongmei
中科院分区：
文献类型：
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作者：
Jiang, Huihui;Hou, Peili;Wang, Hongmei
牛短暂热病毒（Bovine ephemeral fever virus，BEFV）是一种由节肢动物传播的弹状病毒，在世界范围内引起牛和布法罗的短暂热。先前的研究表明，BEFV感染导致诱导宿主细胞凋亡。然而，细胞凋亡在病毒复制中的作用以及BEFV诱导细胞凋亡过程中病毒基因与宿主基因之间的相互作用仍不清楚。本文研究了病毒非结构蛋白α 3与细胞核异质性核糖核蛋白K（hnRNP K）在BEFV诱导的细胞凋亡中的相互作用及其在病毒复制中的作用。α 3基因过表达可激活caspase 3，从而裂解PARP，最终导致细胞凋亡.此外，还测定了BEFV感染BHK-21细胞后，分别用泛半胱天冬酶抑制剂（Z-VAD-FMK）和凋亡诱导剂（CCCP）处理后的病毒滴度，结果表明凋亡促进了病毒的复制。敲低hnRNPK基因可促进BEFV的复制，而过表达hnRNPK基因则相反。更重要的是，hnRNP K的过表达抑制病毒诱导的细胞凋亡。随后发现hnRNP K通过降解病毒α 3基因抑制BEFV的复制，并进一步抑制α 3基因诱导的细胞凋亡。最后，hnRNP K蛋白的表达显着下调后，BEFV感染的BHK-21细胞中的hnRNP K蛋白的降解介导的病毒激活caspase 3。这些结果表明，细胞凋亡在BEFV的复制过程中起着关键作用，病毒α 3基因与宿主hnRNPK基因在BEFV诱导的细胞凋亡中的相互作用促进了BEFV的复制。
Bovine ephemeral fever virus (BEFV) is an arthropod-bome rhabdovirus and causes bovine ephemeral fever of cattle and water buffalo in worldwide. Previous studies have demonstrated that infection with BEFV leads to induction of host cellular apoptosis. However, the role of apoptosis in viral replication and the interaction between viral genes and host genes involved in the process of BEFV-induced apoptosis remains unclear. Herein we investigated the interaction between viral non-structural protein alpha 3 and cellular heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the BEFV-induced apoptosis and its role in virus replication. Overexpression of alpha 3 gene activated caspase 3 and consequently cleaved PARP, ultimately lead to apoptosis. Moreover, virus titer of BHK-21 cells infected with BEFV and then treated respectively by the pan-caspase inhibitor (Z-VAD-FMK) and apoptosis inducer (CCCP) was determined, the results showed that apoptosis promoted viral replication. In addition, knockdown of hnRNP K gene promoted BEFV replication, whereas overexpression of hnRNP K gene had the opposite effects. More importantly, overexpression of hnRNP K inhibited virus-induced apoptosis. Subsequently, it was found that hnRNP K suppressed BEFV replication via degrading viral alpha 3 gene and further inhibited apoptosis induced by alpha 3 gene. Finally, the expression of hnRNP K protein was significantly downregulated upon BEFV infection, and degradation of hnRNP K protein in BHK-21 cells infected with BEFV was mediated by viral activation of caspase 3. Taken together, these results suggest that apoptosis takes a pivotal role in BEFV replication, and interaction between viral alpha 3 gene and host hnRNP K gene in BEFV-induced apoptosis facilitates BEFV replication.