14-3-3ε acts as a proviral factor in highly pathogenic porcine reproductive and respiratory syndrome virus infection
14-3-3ε acts as a proviral factor in highly pathogenic porcine reproductive and respiratory syndrome virus infection
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14-3-3 epsilon 在高致病性猪繁殖与呼吸综合征病毒感染中充当前病毒因子
DOI：
10.1186/s13567-019-0636-0
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发表时间：
2019-02-28
影响因子：
4.4
通讯作者：
Xiao, Yihong
中科院分区：
文献类型：
--
作者：
Cao, Shengliang;Cong, Fangyuan;Xiao, Yihong
高致病性猪繁殖与呼吸综合征病毒（HP-PRRSV）于2006年在我国暴发，由于缺乏有效的疫苗，给养猪业造成了巨大的经济损失。14-3-3蛋白作为潜在的药物靶点，通过靶向特定的途径在人类疾病中引起治疗效果，引起了人们的极大兴趣。在先前的研究中，14-3-3s被鉴定为与PRRSV的非结构蛋白2（NSP 2）相互作用。在本研究中，特定的亚型14-3-3 β被证实与NSP 2相互作用，并在HP-PRRSV TA-12株的复制中发挥作用。在Marc-145细胞和猪肺泡巨噬细胞（PAM）中敲低14-3-3 β引起TA-12复制的显著降低，而稳定过表达14-3-3 β引起TA-12和低致病性PRRSV（LP-PRRSV）CH-1 R复制的显著增加。14-3-3抑制剂difopein也降低了Marc-145细胞和PAM中TA-12和CH-1 R的复制。这些发现与14-3-3 siRNA作为前病毒因子的作用一致，并表明14-3-3 siRNA和difopein是针对PRRSV感染的治疗候选物。
The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) emerged in 2006 in China and caused great economic losses for the swine industry because of the lack of an effective vaccine. 14-3-3 proteins are generating significant interest as potential drug targets by allowing the targeting of specific pathways to elicit therapeutic effects in human diseases. In a previous study, 14-3-3s were identified to interact with non-structural protein 2 (NSP2) of PRRSV. In the present study, the specific subtype 14-3-3 epsilon was confirmed to interact with NSP2 and play a role in the replication of the HP-PRRSV TA-12 strain. Knockdown of 14-3-3 epsilon in Marc-145 cells and porcine alveolar macrophages (PAMs) caused a significant decrease in TA-12 replication, while stable overexpression of 14-3-3 epsilon caused a significant increase in the replication of TA-12 and low pathogenic PRRSV (LP-PRRSV) CH-1R. The 14-3-3 inhibitor difopein also decreased TA-12 and CH-1R replication in Marc-145 cells and PAMs. These findings are consistent with 14-3-3 epsilon acting as a proviral factor and suggest that 14-3-3 epsilon siRNA and difopein are therapeutic candidates against PRRSV infection.