ERK inhibition aids IFN-& beta; promoter activation during EV71 infection by blocking CRYAB degradation in SH-SY5Y cells

作者全名："Chen, Dengming; Chen, Cheng; Tan, Jingyu; Yang, Jing; Chen, Bangtao"

作者地址："[Chen, Dengming] Chongqing Med Univ, Emergency & Crit Care Med Ctr, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Chen, Cheng] Chongqing Univ, Dept Gastroenterol, Chongqing Key Lab Translat Res Canc Metastasis & I, Canc Hosp, Chongqing 400044, Peoples R China; [Tan, Jingyu] Chongqing Univ, Phys Examinat Ctr, Canc Hosp, Chongqing 400044, Peoples R China; [Yang, Jing; Chen, Bangtao] Chong Univ, Sch Med, Dept Dermatol, Chongqing Univ,Three Gorges Hosp, Chongqing 400030, Peoples R China; [Chen, Bangtao] Chongqing Univ, Three Gorges Hosp, Dept Dermatol, 165 Xincheng Rd, Chongqing 400030, Peoples R China"

通信作者："Chen, BT (通讯作者)，Chongqing Univ, Three Gorges Hosp, Dept Dermatol, 165 Xincheng Rd, Chongqing 400030, Peoples R China."

来源：PATHOGENS AND DISEASE

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001019435400002

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：81

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：alphaB-crystallin; enterovirus 71; extracellular signal-regulated kinases; interferon; neural precursor cell-expressed developmentally downregulated 4-like

摘要："Enterovirus 71 (EV71) can cause severe hand-foot-and-mouth disease with neurological complications. It has evolved multiple mechanisms to compromise the host type I interferon (IFN-I) response. In neuronal cells, EV71-mediated IFN-I antagonism may be associated with neural precursor cell-expressed developmentally downregulated 4-like (Nedd4L), the E3 ubiquitin ligase that can interact with alphaB-crystallin (CRYAB) in the regulation of Nav1.5 stability. Here, we investigated the effect of CRYAB stability on IFN-& beta; promoter activity in neuronal SH-SY5Y cells infected with EV71, and its relations to Nedd4 L and extracellular signal-regulated kinases (ERK). Results showed that EV71 infection significantly caused CRYAB degradation via the Nedd4L-proteasome pathway, which required ERK-mediated phosphorylation of Serine 45 in CRYAB. Subsequently, it was observed that siRNA- or EV71-mediated CRYAB reduction limited Poly(dAT)-activated IFN-& beta; promoter, and CRYAB stabilisation by U0126-mediated inhibition of ERK activation remarkably enhanced the activity of IFN-& beta; promoter upon EV71 challenge. Collectively, we elucidate a novel mechanism by which ERK activation contributes to EV71 immune escape via CRYAB/IFN-& beta; axis in SH-SY5Y cells, indicating that perturbing ERK activation is desirable for anti-EV71 therapy. This study shows that perturbing ERK activation is desirable for anti-EV71 therapy by blocking CRYAB degradation and thus facilitating IFN-& beta; promoter activation."

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