Lu Yanfang, Hou Hongyan, Wang Feng, Qiao Long, Wang Xiong, Yu Jing, Liu Weiyong, Sun Ziyong
Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer Biology Research Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Virology. 2016 Sep;496:28-34. doi: 10.1016/j.virol.2016.05.013. Epub 2016 May 27.
Enterovirus 71 (EV71) infection can cause severe diseases, and is becoming increasingly common in children. In the current study, we carried out yeast two-hybrid assays to screen human proteins that could interact with 3A protein of EV71. Human β3 subunit of Na(+)/K(+)-ATPase (ATP1B3) protein was demonstrated to interact with the 3A protein of EV71. Although 3A protein had no effect on the expression of ATP1B3, EV71 infection resulted in elevated expression of ATP1B3 in RD cell line, both on messenger RNA (mRNA) and protein levels. Interestingly, knockdown of ATP1B3 could significantly increase the replication of EV71, whereas overexpression of ATP1B3 significantly suppressed the replication of EV71 in RD cells. Furthermore, we demonstrated that the expression of ATP1B3 could induce the production of type-I interferons. Our study demonstrated that ATP1B3 inhibit EV71 replication by enhancing the production of type-I interferons, which could act as a potential therapeutic target in EV71 infection.
肠道病毒71型（EV71）感染可导致严重疾病，且在儿童中越来越常见。在本研究中，我们进行了酵母双杂交试验，以筛选可与EV71的3A蛋白相互作用的人类蛋白。结果表明，人类钠钾ATP酶（ATP1B3）的β3亚基蛋白可与EV71的3A蛋白相互作用。虽然3A蛋白对ATP1B3的表达没有影响，但EV71感染导致RD细胞系中ATP1B3在信使核糖核酸（mRNA）和蛋白质水平上的表达均升高。有趣的是，敲低ATP1B3可显著增加EV71的复制，而ATP1B3的过表达则显著抑制RD细胞中EV71的复制。此外，我们证明ATP1B3的表达可诱导I型干扰素的产生。我们的研究表明，ATP1B3通过增强I型干扰素的产生来抑制EV71复制，这可能成为EV71感染的潜在治疗靶点。
