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GRAMD4 regulates PEDV-induced cell apoptosis inhibiting virus replication via the endoplasmic reticulum stress pathway.
Xu, Xingang; Liu, Yi; Gao, Jie; Shi, Xiaojie; Yan, Yuchao; Yang, Naling; Wang, Quanqiong; Zhang, Qi.
  • Xu X; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Liu Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Gao J; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Shi X; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Yan Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Yang N; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Wang Q; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Zhang Q; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: zhangqi77@nwsuaf.edu.cn.
Vet Microbiol ; 279: 109666, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2287296
ABSTRACT
Porcine epidemic diarrhea (PED) caused by the porcine epidemic diarrhea virus (PEDV) has caused huge losses in the swine industry worldwide. Glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4 (GRAMD4) is a proapoptotic protein, which replaced p53 inducing mitochondrial apoptosis. However, the relationship between GRAMD4 and PEDV has not been reported. Here, we aimed to investigate the potential role of GRAMD4 during PEDV infection. In this study, we used co-immunoprecipitation (co-IP) and mass spectrometry to identify GRAMD4 interaction with PEDV non-structural protein 6 (NSP6). Immunoprecipitation and laser confocal microscopy were utilized to demonstrate that GRAMD4 interacts with NSP6. NSP6 reduces GRAMD4 production through PERK and IRE1 pathway-mediated apoptosis. We demonstrated that overexpression of GRAMD4 effectively impaired the replication of PEDV, whereas knockdown of GRAMD4 facilitated the replication of PEDV. Overexpression of GRAMD4 increased GRP78, phosphorylated PERK (p-PERK), phosphorylated IRE1(p-IRE1) levels, promoted CHOP, phosphorylated JNK (p-JNK), Bax expression, caspase 9 and caspase 3 cleavage, and inhibited Bcl-2 production. Knockdown of GRAMD4 has the opposite effect. Finally, deletion of the GRAM domain of GRAMD4 cannot cause endoplasmic reticulum stress (ER stress)-mediated apoptosis and inhibit virus replication. In conclusion, these studies revealed the mechanism by which GRAMD4 was associated with ER stress and apoptosis regulating PEDV replication. NSP6 acted as a potential down-regulator of GRAMD4 and promoted the degradation of GRAMD4. GRAMD4 played a role in facilitating apoptosis and restricting virus replication, and the GRAM domain was required. These findings provided a reference for host-PEDV interactions and offered the possibility for PEDV decontamination and prevention.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Swine Diseases / Coronavirus Infections / Porcine epidemic diarrhea virus Type of study: Prognostic study Limits: Animals Language: English Journal: Vet Microbiol Year: 2023 Document Type: Article Affiliation country: J.vetmic.2023.109666

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Swine Diseases / Coronavirus Infections / Porcine epidemic diarrhea virus Type of study: Prognostic study Limits: Animals Language: English Journal: Vet Microbiol Year: 2023 Document Type: Article Affiliation country: J.vetmic.2023.109666