Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism
ABSTRACT In the 21st century, several human and swine coronaviruses (CoVs) have emerged suddenly and caused great damage to people's lives and property. The porcine epidemic diarrhea virus (PEDV), leading to enormous economic losses to the pork industry and remains a large challenge. PEDV showe...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03739-21 |
| _version_ | 1818478251259985920 |
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| author | Zhiwei Li Zhiqian Ma Linfang Dong Ting Yang Yang Li Dian Jiao Weiguo Han Haixue Zheng Shuqi Xiao |
| author_facet | Zhiwei Li Zhiqian Ma Linfang Dong Ting Yang Yang Li Dian Jiao Weiguo Han Haixue Zheng Shuqi Xiao |
| author_sort | Zhiwei Li |
| collection | DOAJ |
| description | ABSTRACT In the 21st century, several human and swine coronaviruses (CoVs) have emerged suddenly and caused great damage to people's lives and property. The porcine epidemic diarrhea virus (PEDV), leading to enormous economic losses to the pork industry and remains a large challenge. PEDV showed extensive cell tropism, and we cannot ignore the potential risk of cross-species transmission. However, the mechanism of adaptation and cell tropism of PEDV remains largely unknown and in vitro isolation of PEDV remains a huge challenge, which seriously impedes the development of vaccines. In this study, we confirmed that the spike (S) protein determines the adaptability of PEDV to monkey Vero cells and LLC-PK1 porcine cells, and isolated exchange of S1 and S2 subunits of adaptive strains did not make PEDV adapt to cells. Further, we found that the cellular adaptability of rCH/SX/2016-SHNXP depends on S1 and the first half of S2 (S3), and the 803L and 976H of the S2 subunit are critical for rCH/SX/2016-S1HNXP+S3HNXP adaptation to Vero cells. These findings highlight the decisive role of PEDV S protein in cell tropism and the potential role of coronaviruses S protein in cross-species transmissibility. Besides, our work also provides some different insight into finding PEDV receptors and developing PEDV and other coronaviruses vaccines. IMPORTANCE CoVs can spill from an animal reservoir into a naive host to cause diseases in humans or domestic animals. PEDV results in high mortality in piglets, which has caused immense economic losses in the pork industry. Virus isolation is the first step in studying viral pathogenesis and developing effective vaccines. However, the molecular mechanism of PEDV cell tropism is largely unknown, and isolation of endemic PEDV strains remains a major challenge. This study confirmed that the S gene is the decisive gene of PEDV adaptability to monkey Vero cells and porcine LLC-PK1 cells by the PEDV reverse genetics system. Isolated exchange of S1 and S2 of adaptive strains did not make PEDV adapt to cells, and the 803L and 976H of S2 subunit are critical for rCH/SX/2016-S1HNXP+S3HNXP adaptation to Vero cells. These results illustrate the decisive role of PEDV S protein in cell tropism and highlight the potential role of coronaviruses S protein in cross-species transmissibility. Besides, our finding also provides some unique insight into identifying PEDV functional receptors and has guiding significance for developing PEDV and other coronavirus vaccines. |
| first_indexed | 2024-12-10T09:45:31Z |
| format | Article |
| id | doaj.art-a89c2aad35c74bbe9dcd2504d3e0b125 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-10T09:45:31Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-a89c2aad35c74bbe9dcd2504d3e0b1252022-12-22T01:53:51ZengAmerican Society for MicrobiologymBio2150-75112022-04-0113210.1128/mbio.03739-21Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell TropismZhiwei Li0Zhiqian Ma1Linfang Dong2Ting Yang3Yang Li4Dian Jiao5Weiguo Han6Haixue Zheng7Shuqi Xiao8State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaABSTRACT In the 21st century, several human and swine coronaviruses (CoVs) have emerged suddenly and caused great damage to people's lives and property. The porcine epidemic diarrhea virus (PEDV), leading to enormous economic losses to the pork industry and remains a large challenge. PEDV showed extensive cell tropism, and we cannot ignore the potential risk of cross-species transmission. However, the mechanism of adaptation and cell tropism of PEDV remains largely unknown and in vitro isolation of PEDV remains a huge challenge, which seriously impedes the development of vaccines. In this study, we confirmed that the spike (S) protein determines the adaptability of PEDV to monkey Vero cells and LLC-PK1 porcine cells, and isolated exchange of S1 and S2 subunits of adaptive strains did not make PEDV adapt to cells. Further, we found that the cellular adaptability of rCH/SX/2016-SHNXP depends on S1 and the first half of S2 (S3), and the 803L and 976H of the S2 subunit are critical for rCH/SX/2016-S1HNXP+S3HNXP adaptation to Vero cells. These findings highlight the decisive role of PEDV S protein in cell tropism and the potential role of coronaviruses S protein in cross-species transmissibility. Besides, our work also provides some different insight into finding PEDV receptors and developing PEDV and other coronaviruses vaccines. IMPORTANCE CoVs can spill from an animal reservoir into a naive host to cause diseases in humans or domestic animals. PEDV results in high mortality in piglets, which has caused immense economic losses in the pork industry. Virus isolation is the first step in studying viral pathogenesis and developing effective vaccines. However, the molecular mechanism of PEDV cell tropism is largely unknown, and isolation of endemic PEDV strains remains a major challenge. This study confirmed that the S gene is the decisive gene of PEDV adaptability to monkey Vero cells and porcine LLC-PK1 cells by the PEDV reverse genetics system. Isolated exchange of S1 and S2 of adaptive strains did not make PEDV adapt to cells, and the 803L and 976H of S2 subunit are critical for rCH/SX/2016-S1HNXP+S3HNXP adaptation to Vero cells. These results illustrate the decisive role of PEDV S protein in cell tropism and highlight the potential role of coronaviruses S protein in cross-species transmissibility. Besides, our finding also provides some unique insight into identifying PEDV functional receptors and has guiding significance for developing PEDV and other coronavirus vaccines.https://journals.asm.org/doi/10.1128/mbio.03739-21spikecellular tropismcoronavirusporcine epidemic diarrhea virusreverse genetic analysis |
| spellingShingle | Zhiwei Li Zhiqian Ma Linfang Dong Ting Yang Yang Li Dian Jiao Weiguo Han Haixue Zheng Shuqi Xiao Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism mBio spike cellular tropism coronavirus porcine epidemic diarrhea virus reverse genetic analysis |
| title | Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism |
| title_full | Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism |
| title_fullStr | Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism |
| title_full_unstemmed | Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism |
| title_short | Molecular Mechanism of Porcine Epidemic Diarrhea Virus Cell Tropism |
| title_sort | molecular mechanism of porcine epidemic diarrhea virus cell tropism |
| topic | spike cellular tropism coronavirus porcine epidemic diarrhea virus reverse genetic analysis |
| url | https://journals.asm.org/doi/10.1128/mbio.03739-21 |
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