Cynomolgus Monkeys (Macaca fascicularis) as an Experimental Infection Model for Human Group A Rotavirus

Abstract

Group A rotaviruses (RVA) are one of the most common causes of severe acute gastroenteritis in infants worldwide. Rotaviruses spread from person to person, mainly by faecal–oral transmission. Almost all unvaccinated children may become infected with RVA in the first two years of life. The establishment of an experimental monkey model with RVA is important to evaluate new therapeutic approaches. In this study, we demonstrated viral shedding and viraemia in juvenile–adult Macaca fascicularis orally inoculated with Wa RVA prototype. Nine monkeys were inoculated orally: seven animals with human RVA and two control animals with saline solution. During the study, the monkeys were clinically monitored, and faeces and blood samples were tested for RVA infection. In general, the inoculated animals developed an oligosymptomatic infection pattern. The main clinical symptoms observed were diarrhoea in two monkeys for three days, associated with a reduction in plasmatic potassium content. Viral RNA was detected in seven faecal and five sera samples from inoculated animals, suggesting virus replication. Cynomolgus monkeys are susceptible hosts for human Wa RVA infection. When inoculated orally, they presented self-limited diarrhoea associated with presence of RVA infectious particles in faeces. Thus, cynomolgus monkeys may be useful as animal models to evaluate the efficacy of new antiviral approaches.

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

“…Due to the genetic proximity of non-human primates (NHP), including vervet monkeys, cynomolgus monkeys, rhesus macaques, pig-tailed macaques, chimpanzees, and baboons, to humans, they expectedly share many anatomical, immunological, and physiological similarities. NHPs have served as important experimental models for enteric viral research, as they recapitulate the pathogenesis of infections in humans to a greater degree than other animal models [ 26 , 174 , 175 , 176 ]. Baboons and vervet monkeys infected with HRV exhibit viral shedding and elevated level of virus neutralizing antibodies [ 175 ], and cynomolgus monkeys similarly exhibit self-limiting diarrhea and shedding of infectious virus [ 26 , 27 ].…”

“…NHPs have served as important experimental models for enteric viral research, as they recapitulate the pathogenesis of infections in humans to a greater degree than other animal models [ 26 , 174 , 175 , 176 ]. Baboons and vervet monkeys infected with HRV exhibit viral shedding and elevated level of virus neutralizing antibodies [ 175 ], and cynomolgus monkeys similarly exhibit self-limiting diarrhea and shedding of infectious virus [ 26 , 27 ]. Chimpanzees have been used for HuNoV infections, wherein the duration of viral shedding and serum antibody responses in this model are similar to those in humans [ 40 , 177 ].…”

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…NHPs share many anatomical, immunological, and physiological similarities with humans and thus are excellent models to recapitulate the pathogenesis of enteric virus infections and/or co-infection in humans [143]. NHPs are susceptible to some human enteric viruses, making studies of human viral co-infections potentially tractable [144,145]. Indeed, many simian viruses isolated from NHPs in the wild or in captivity, including simian RV and rhesus enteric caliciviruses, are also important pathogens for in vitro and in vivo studies, such as viral receptor identification and determination of adaptive immune responses [146][147][148].…”

The employment of cynomolgus monkey as proprioceptive deficit model of the anterior cruciate ligament

“…Therefore, increasing attention has been applied to primates, as they display the closest relationship with humans. 20 Among them, cynomolgus monkeys are one of the most suitable models due to their high genetic similarity, and similar anatomies and physiologies to humans. 21 Besides, cynomologus monkeys stand and walk only on their hind limbs, and because of their nature, they stand and walk longer than the aforementioned animals, hence sharing higher similarities with humans in the aspects of standing and walking.…”