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A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses

A neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses

Authors :
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
Source :
Emerging Microbes and Infections, Vol 3, Iss 1, Pp 1-12 (2014)
Publication Year :
2014
Publisher :
Taylor & Francis Group, 2014.

Abstract

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.

Details

Language :
English
ISSN :
22221751
Volume :
3
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Emerging Microbes and Infections
Publication Type :
Academic Journal
Accession number :
edsdoj.983f0d9d45d54e82839649d0571d08e3
Document Type :
article
Full Text :
https://doi.org/10.1038/emi.2014.35