A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses
Vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. Here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain BJ110, which has a C4 genotype. Porcine...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2014-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1038/emi.2014.35 |
| _version_ | 1827812595301613568 |
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| author | Xingdong Yang Guohua Li Ke Wen Tammy Bui Fangning Liu Jacob Kocher Bernard S Jortner Marlice Vonck Kevin Pelzer Jie Deng Runan Zhu Yuyun Li Yuan Qian Lijuan Yuan |
| author_facet | Xingdong Yang Guohua Li Ke Wen Tammy Bui Fangning Liu Jacob Kocher Bernard S Jortner Marlice Vonck Kevin Pelzer Jie Deng Runan Zhu Yuyun Li Yuan Qian Lijuan Yuan |
| author_sort | Xingdong Yang |
| collection | DOAJ |
| description | Vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. Here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain BJ110, which has a C4 genotype. Porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. Oral and combined oral–nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×108 fluorescence forming units (FFU) resulted in shedding up to 18 days post-infection, with viral titers in rectal swab samples peaking at 2.22×108 viral RNA copies/mL. Viral capsid proteins were detected in enterocytes within the small intestines on post-infection days (PIDs) 7 and 14. Additionally, viral RNA was detected in intestinal and extra-intestinal tissues, including the central nervous system, the lung and cardiac muscle. The infected neonatal gnotobiotic pigs developed fever, forelimb weakness, rapid breathing and some hand, foot and mouth disease symptoms. Flow cytometry analysis revealed increased frequencies of both CD4+ and CD8+ IFN-γ-producing T cells in the brain and the blood on PID 14, but reduced frequencies were observed in the lung. Furthermore, high titers of serum virus-neutralizing antibodies were generated in both orally and combined oral–nasally infected pigs on PIDs 7, 14, 21 and 28. Together, these results demonstrate that neonatal gnotobiotic pigs represent a novel animal model for evaluating vaccines for human enterovirus 71 and for understanding the pathogenesis of this virus and the associated immune responses. |
| first_indexed | 2024-03-11T23:20:43Z |
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| id | doaj.art-983f0d9d45d54e82839649d0571d08e3 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-11T23:20:43Z |
| publishDate | 2014-01-01 |
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| series | Emerging Microbes and Infections |
| spelling | doaj.art-983f0d9d45d54e82839649d0571d08e32023-09-20T14:20:33ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512014-01-013111210.1038/emi.2014.35A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responsesXingdong Yang0Guohua Li1Ke Wen2Tammy Bui3Fangning Liu4Jacob Kocher5Bernard S Jortner6Marlice Vonck7Kevin Pelzer8Jie Deng9Runan Zhu10Yuyun Li11Yuan Qian12Lijuan Yuan13Department of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USADepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USALaboratory of Virology, Capital Institute of Pediatrics, Beijing 100020, ChinaLaboratory of Virology, Capital Institute of Pediatrics, Beijing 100020, ChinaLaboratory of Virology, Capital Institute of Pediatrics, Beijing 100020, ChinaLaboratory of Virology, Capital Institute of Pediatrics, Beijing 100020, ChinaDepartment of Biomedical Sciences and Pathobiology, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0913, USAVaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. Here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain BJ110, which has a C4 genotype. Porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. Oral and combined oral–nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×108 fluorescence forming units (FFU) resulted in shedding up to 18 days post-infection, with viral titers in rectal swab samples peaking at 2.22×108 viral RNA copies/mL. Viral capsid proteins were detected in enterocytes within the small intestines on post-infection days (PIDs) 7 and 14. Additionally, viral RNA was detected in intestinal and extra-intestinal tissues, including the central nervous system, the lung and cardiac muscle. The infected neonatal gnotobiotic pigs developed fever, forelimb weakness, rapid breathing and some hand, foot and mouth disease symptoms. Flow cytometry analysis revealed increased frequencies of both CD4+ and CD8+ IFN-γ-producing T cells in the brain and the blood on PID 14, but reduced frequencies were observed in the lung. Furthermore, high titers of serum virus-neutralizing antibodies were generated in both orally and combined oral–nasally infected pigs on PIDs 7, 14, 21 and 28. Together, these results demonstrate that neonatal gnotobiotic pigs represent a novel animal model for evaluating vaccines for human enterovirus 71 and for understanding the pathogenesis of this virus and the associated immune responses.https://www.tandfonline.com/doi/10.1038/emi.2014.35adaptive immune responsesanimal modelhuman enterovirus 71neonatal gnotobiotic pigspathogenesisvaccine evaluation |
| spellingShingle | Xingdong Yang Guohua Li Ke Wen Tammy Bui Fangning Liu Jacob Kocher Bernard S Jortner Marlice Vonck Kevin Pelzer Jie Deng Runan Zhu Yuyun Li Yuan Qian Lijuan Yuan A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses Emerging Microbes and Infections adaptive immune responses animal model human enterovirus 71 neonatal gnotobiotic pigs pathogenesis vaccine evaluation |
| title | A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| title_full | A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| title_fullStr | A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| title_full_unstemmed | A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| title_short | A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| title_sort | neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses |
| topic | adaptive immune responses animal model human enterovirus 71 neonatal gnotobiotic pigs pathogenesis vaccine evaluation |
| url | https://www.tandfonline.com/doi/10.1038/emi.2014.35 |
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