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Effective inhibition of PDCoV infection in chimeric APN gene-edited neonatal pigs

文献类型： 外文期刊

作者： Li, Jizong 1 ; Zhou, Jian 7 ; Zhang, Tianyi 7 ; Wu, Heyong 7 ; Li, Feng 7 ; Qi, Chunyun 7 ; Fan, Liyuan 1 ; Yuan, Xuesong 1 ; Wang, Wei 1 ; Guo, Rongli 1 ; Fan, Baochao 1 ; Tang, Xiaochun 7 ; Pang, Daxin 7 ; Ouyang, Hongsheng 7 ; Xie, Zicong 7 ; Li, Bin 1 ;

作者机构： 1.Minist Agr, Key Lab Vet Biol Engn & Technol, Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing, Peoples R China

2.Minist Sci & Technol, Jiangsu Key Lab Food Qual & Safety, State Key Lab Cultivat Base, Nanjing, Peoples R China

3.Jiangsu Univ, Inst Life Sci, Sch Food & Biol Engn, Zhenjiang 212000, Jiangsu, Peoples R China

4.Nanjing Agr Univ, Coll Vet Med, Nanjing, Peoples R China

5.Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Peoples R China

6.Guotai Taizhou Ctr Technol Innovat Vet Biol, Taizhou, Peoples R China

7.Jilin Univ, Coll Anim Sci, Anim Genome Editing Technol Innovat Ctr, Key Lab Zoonoses Res,Minist Educ, Changchun, Jilin, Peoples R China

关键词： porcine deltacoronavirus; aminopeptidase N; viral receptor; APN; disease resistance

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：4.0； 五年影响因子：4.0 ）

ISSN： 0022-538X

年卷期： 2024 年 98 卷 8 期

页码：

收录情况： SCI

摘要： Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, is a serious threat to piglets and has zoonotic potential. Here, we aimed to further explore the role of aminopeptidase N (APN) as a receptor for PDCoV and test the inhibitory effect of a chimeric APN protein strategy on PDCoV infection. PK-15 cells and LLC-PK1 cells expressing chimeric APN were selected and infected with PDCoV. Viral replication was significantly decreased in these chimeric APN cells compared with that in control group cells. To further characterize the effect of the chimeric APN strategy on PDCoV infection in vitro, primary intestinal epithelial cells isolated from chimeric APN pigs were inoculated with PDCoV. Viral challenge of these cells led to decreased PDCoV infection. More importantly, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. Taken together, these findings deepen our understanding of the mechanism of PDCoV infection and provide a valuable model for the production of disease-resistant animals.IMPORTANCEPorcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhea in piglets and possesses the potential to infect humans. However, there are currently no effective measures for the prevention or control of PDCoV infection. Here, we have developed PK-15 cells, LLC-PK1 cells, and primary intestinal epithelial cells expressing chimeric APN, and viral challenge of these cells led to decreased PDCoV infection. Furthermore, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. These data show that chimeric APN is a promising strategy to combat PDCoV infection. Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhea in piglets and possesses the potential to infect humans. However, there are currently no effective measures for the prevention or control of PDCoV infection. Here, we have developed PK-15 cells, LLC-PK1 cells, and primary intestinal epithelial cells expressing chimeric APN, and viral challenge of these cells led to decreased PDCoV infection. Furthermore, virally challenged chimeric APN neonatal piglets displayed reduced viral load, significantly fewer microscopic lesions in the intestinal tissue, and no diarrhea. These data show that chimeric APN is a promising strategy to combat PDCoV infection.

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