Neonatal rhesus monkeys as an animal model for rotavirus infection

• Published in: World journal of gastroenterology : WJG 2018-12, Vol.24 (45), p.5109-5119
• Main Authors: Yin, Na, Yang, Feng-Mei, Qiao, Hong-Tu, Zhou, Yan, Duan, Su-Qin, Lin, Xiao-Chen, Wu, Jin-Yuan, Xie, Yu-Ping, He, Zhan-Long, Sun, Mao-Sheng, Li, Hong-Jun
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Basic Study; Diarrhea - diagnosis; Diarrhea - immunology; Diarrhea - virology; Disease Models, Animal; Epithelial Cells - immunology; Epithelial Cells - pathology; Epithelial Cells - virology; Feces - virology; Humans; Intestine, Small - cytology; Intestine, Small - immunology; Intestine, Small - pathology; Intestine, Small - virology; Macaca mulatta; RNA, Viral - isolation & purification; Rotavirus - genetics; Rotavirus - immunology; Rotavirus - pathogenicity; Rotavirus Infections - diagnosis; Rotavirus Infections - immunology; Rotavirus Infections - virology; Virus Shedding
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v24.i45.5109

To establish a rotavirus (RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines. Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV ( 10 PFUs/mL, 10 PFUs/mL, or 10 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay. The RV monkey model showed typical clinical diarrhea symptoms in the 10 PFUs SA11 group, where we observed diarrhea 1-4 d post infection (dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 10 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 10 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi. Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.