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Porcine ANTXR1, Heparan Sulfate and Neu5Gc act as entry factors for Seneca Valley virus invasion

Wenda Tang, Yanchao Wang, Xiaolan Qi, Fengxing Gu, Kangli Li, Haitang Han, Xuguang Du, Zixiang Zhu, Sen Wu, View ORCID ProfileYaofeng Zhao, View ORCID ProfileHaixue Zheng
doi: https://doi.org/10.1101/2022.06.14.496051
Wenda Tang
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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Yanchao Wang
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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Xiaolan Qi
2State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
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Fengxing Gu
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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Kangli Li
2State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
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Haitang Han
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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Xuguang Du
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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Zixiang Zhu
2State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
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  • For correspondence: zhenghaixue@caas.cn yaofengzhao@cau.edu.cn swu@cau.edu.cn zhuzixiang@caas.cn
Sen Wu
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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  • For correspondence: zhenghaixue@caas.cn yaofengzhao@cau.edu.cn swu@cau.edu.cn zhuzixiang@caas.cn
Yaofeng Zhao
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, Frontier Science Center for Molecular Design Breeding and National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, P. R. China
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  • ORCID record for Yaofeng Zhao
  • For correspondence: zhenghaixue@caas.cn yaofengzhao@cau.edu.cn swu@cau.edu.cn zhuzixiang@caas.cn
Haixue Zheng
2State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
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  • ORCID record for Haixue Zheng
  • For correspondence: zhenghaixue@caas.cn yaofengzhao@cau.edu.cn swu@cau.edu.cn zhuzixiang@caas.cn
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Abstract

Seneca Valley virus (SVV) disease is a newly emerging infectious disease of pigs caused by SVV, which seriously endangers the pig industry. This study was set out to identify the essential host factors required for SVV entering porcine cells. Using a CRISPR/Cas9 library containing 93,859 sgRNAs that were designed to target approximately 22,707 porcine genes, we generated mutated porcine cell libraries, which were subjected to SVV challenge for enrichment of cells resistant to SVV infection. These resistant cells were subsequently analyzed to identify genes essential for SVV infection. We demonstrated that ANTXR1, a type I transmembrane protein encoded by ANTXR1 , heparan sulfate (HS), glycosaminoglycans modified by acetylation and sulfation of HS2ST1, and Neu5Gc, a non-human sialic acid catalyzed by CMAH, were the essential host factors for SVV entry into porcine cells. These results will be helpful to elucidate the pathogenesis of SVV and the development of prevention and control measures.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 16, 2022.
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Porcine ANTXR1, Heparan Sulfate and Neu5Gc act as entry factors for Seneca Valley virus invasion
Wenda Tang, Yanchao Wang, Xiaolan Qi, Fengxing Gu, Kangli Li, Haitang Han, Xuguang Du, Zixiang Zhu, Sen Wu, Yaofeng Zhao, Haixue Zheng
bioRxiv 2022.06.14.496051; doi: https://doi.org/10.1101/2022.06.14.496051
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Porcine ANTXR1, Heparan Sulfate and Neu5Gc act as entry factors for Seneca Valley virus invasion
Wenda Tang, Yanchao Wang, Xiaolan Qi, Fengxing Gu, Kangli Li, Haitang Han, Xuguang Du, Zixiang Zhu, Sen Wu, Yaofeng Zhao, Haixue Zheng
bioRxiv 2022.06.14.496051; doi: https://doi.org/10.1101/2022.06.14.496051

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