2. Academic Validation
  3. HSP90AB1 is a host factor that promotes Porcine deltacoronavirus replication

HSP90AB1 is a host factor that promotes Porcine deltacoronavirus replication

  • J Biol Chem. 2023 Dec 11:105536. doi: 10.1016/j.jbc.2023.105536.
Yujia Zhao 1,  Jianlin Yuan 2,  Dai Xiao 3,  Luwen Zhang 4,  Cheng Li 5,  Jingfei Hu 6,  Rui Chen 7,  Daili Song 8,  Yiping Wen 9,  Rui Wu 10,  Qin Zhao 11,  Senyan Du 12,  Qigui Yan 13,  Xinfeng Han 14,  Xintian Wen 15,  Sanjie Cao 16,  Xiaobo Huang 17
Affiliations

Affiliations

  • 1 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Laboratory Animal Center, Zunyi Medical University, Zunyi, 563000, China. Electronic address: zhaoyujia2015@163.com.
  • 2 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: yuanjianlin715@163.com.
  • 3 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: 15838585575@163.com.
  • 4 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: zlw1655468752@qq.com.
  • 5 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: 1247695208@qq.com.
  • 6 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: Hu_Jingfei0127@163.com.
  • 7 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: 18102341339@163.com.
  • 8 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: song2737503048@163.com.
  • 9 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: yueliang5189@163.com.
  • 10 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: wurui1977@163.com.
  • 11 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: zhao.qin@sicau.edu.cn.
  • 12 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: senyandu@163.com.
  • 13 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: yanqigui@126.com.
  • 14 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: hanxinf@163.com.
  • 15 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: xintian3211@126.com.
  • 16 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Sichuan Science-observation Experiment Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu 611130, China; National Animal Experiments Teaching Demonstration Center, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: csanjie@sicau.edu.cn.
  • 17 Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Sichuan Science-observation Experiment Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu 611130, China; National Animal Experiments Teaching Demonstration Center, Sichuan Agricultural University, Chengdu 611130, China. Electronic address: rsghb110@126.com.
PMID: 38092149 DOI: 10.1016/j.jbc.2023.105536
Abstract

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus. It causes mortality in neonatal piglets and is of growing concern because of its broad host range, including humans. To date, the mechanism of PDCoV Infection remains poorly understood. Here, based on a genome-wide CRISPR screen of PDCoV-infected cells, we found that HSP90AB1 promotes PDCoV Infection. Knockdown or knockout of HSP90AB1 in LLC-PK cells resulted in a significantly suppressed PDCoV Infection. Infected cells treated with HSP90 inhibitors 17-AAG and VER-82576 also showed a significantly suppressed PDCoV Infection, although KW-2478, which does not affect the ATPase activity of HSP90AB1, had no effect on PDCoV Infection. We found that HSP90AB1 interacts with the N, NS7, and NSP10 proteins of PDCoV. We further evaluated the interaction between N and HSP90AB1 and found that the C-tail domain of the N protein is the HSP90AB1-interacting domain. Further studies showed that HSP90AB1 protects N protein from degradation via the Proteasome pathway. In summary, our results reveal a key role for HSP90AB1 in the mechanism of PDCoV Infection and contribute to provide new host targets for PDCoV Antiviral research.

Keywords

CRISPR screening; HSP90AB1; PDCoV; interaction; nucleocapsid protein; protein stability.

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