Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5109
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
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 ( 107 PFUs/mL, 106 PFUs/mL, or 105 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 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 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.
Core tip: Rotavirus (RV) is one of the main pathogens responsible for severe diarrhea in children under 5 years of age. Vaccine-induced immunity is an effective way to block RV disease. 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 these vaccines. Our current study has indicated that RV SA11 can lead to obvious diarrhea and pathological changes in the intestine of neonatal rhesus monkeys. The RV infection model we established is useful for us to further investigate the RV infection mechanism and the associated immune mechanisms in human infants and evaluate the cross protection of potential HRV vaccine candidates.