Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2018; 24(45): 5109-5119
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5109
Neonatal rhesus monkeys as an animal model for rotavirus infection
Na Yin, Feng-Mei Yang, Hong-Tu Qiao, Yan Zhou, Su-Qin Duan, Xiao-Chen Lin, Jin-Yuan Wu, Yu-Ping Xie, Zhan-Long He, Mao-Sheng Sun, Hong-Jun Li
Na Yin, Hong-Tu Qiao, Yan Zhou, Xiao-Chen Lin, Jin-Yuan Wu, Yu-Ping Xie, Mao-Sheng Sun, Hong-Jun Li, Department of Molecular Biology, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming 650118, Yunnan Province, China
Feng-Mei Yang, Su-Qin Duan, Zhan-Long He, Primate Experimental Center of the Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming 650118, Yunnan Province, China
Author contributions: Yin N conceived the idea; Sun MS and Li HJ performed the experiments; Zhou Y, He ZL, and Li HJ contributed reagents and funds; Yang FM, Qiao HT, and Duan SQ performed the animal experiment; Wu JY performed all ELISA experiments; Zhou Y and Xie YP performed the viral RNA extraction and qRT-PCR assay experiments; Qiao HT and Lin XC performed the immunofluorescence experiments; Yin N, Yang FM, Zhou Y, and Li HJ drafted, read, corrected, and approved the manuscript; all authors reviewed the manuscript.
Supported by the CAMS Initiative for Innovative Medicine, No. 2016-I2M-1-019; National Natural Science Foundation of China, No. 31700154; Major Science and Technology Special Project of Yunnan Province (Biomedicine), No. 2018ZF006; Science and Technology Project of Yunnan Province-general program, No. 2016FB034; Science and Technology Innovation Team Project of Kunming, No. 2016-2-R-07674; the Project of National Nonprofit Scientific Institutes Basic Scientific Service Fee, No. 2016ZX310179-4; Science and Technology Project of Yunnan Province, Key New Product Development, No. 2014BC008.
Correspondence author to: Hong-Jun Li, PhD, Academic Research, Department of Molecular Biology, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, No. 935, Jiaoling Road, Kunming 650118, Yunnan Province, China. lihj6912@163.com
Telephone: +86-871-68225391 Fax: +86-871-68225391
Received: August 14, 2018
Peer-review started: August 15, 2018
First decision: October 10, 2018
Revised: October 22, 2018
Accepted: November 7, 2018
Article in press: November 7, 2018
Published online: December 7, 2018
Processing time: 114 Days and 19.2 Hours
ARTICLE HIGHLIGHTS
Research background

Rotavirus (RV) is one of the main pathogens responsible for severe diarrhea in children under 5 years of age. There are currently no specific drugs for the treatment of diarrhea caused by RV infection. Therefore, the development of safe and effective vaccines to control RV infection is particularly important. An effective animal model of RV infection is needed to ensure the effectiveness and safety of these vaccines.

Research motivation

Nonhuman primates are the animals most closely related to humans and have advantages over non-primates as an animal model of RV diarrhea, so development of a nonhuman primate animal model of RV infection is needed to ensure the effectiveness and safety of RV candidate vaccines.

Research objectives

To establish a monkey model of RV infection.

Research methods

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 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.

Research results

The RV monkey model showed typical clinical diarrhea symptoms in the 108 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 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in the 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 of the jejunal villus epithelium was also detectable at 3 dpi.

Research conclusions

We successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys.

Research perspectives

The monkey model of RV infection is useful for us to further investigate the RV infection mechanism and evaluate the protection of potential HRV vaccine candidates.