Experimental Group A Rotaviral Infection in Cynomolgus Monkeys Raised on Formula Diet

Abstract

Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses.Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SAll) viruses and with a rotavirus from a human fecal specimen.However, diarrhea was detected only in very young animals.A number of rotaviral shedding patterns as a function of time were observed.Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals.The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.

Development of a Rotavirus-Shedding Model in Rhesus Macaques, Using a Homologous Wild-Type Rotavirus of a New P Genotype

“…Accordingly, many studies on the pathogenesis of and immunity to such agents have been performed with nonhuman primates. Very few studies, however, have been conducted with rotavirus in any nonhuman primate species (21,23,26,31,36,41,55). A major limitation for performing such studies has been the absence of a challenge strain of simian rotavirus that will consistently result in productive infections in a nonhuman primate species after oral challenge.…”

“…From this analysis it appears that the TUCH VP4 gene diverged from those of other genotypes at a distant point in time. This, coupled with the fact that none of these representative strains share Ͼ89% amino acid homology with the VP4 protein of the new macaque rotavirus (the suggested requirement for inclusion within the same VP4 genotype [14]), indicates that the TUCH strain belongs to a new P genotype, which we tentatively classify as P [23]). …”

“…This region of the VP4 protein of the A34 strain was found to share 79.8% homology with the cognate region of the TUCH VP4 protein, thus confirming that the P type of the A34 strain is distinct from that of TUCH. If upon analysis of the complete sequence of the VP4 gene of the A34 strain, it is confirmed to belong to a new P genotype, the TUCH strain would then be tentatively classified as P [24] rather than P [23].…”

“…The suggestion that the TUCH VP4 gene has evolved from those of other rotaviruses was supported by phylogenetic analysis. Therefore, the TUCH strain was tentatively classified as genotype P [23].…”

“…Although several rotavirus challenge studies have been conducted with these animals, the first of which was reported in 1976 (55), very little is known about rotavirus infections in any nonhuman primate species. Several investigators have reported that oral inoculation of different nonhuman primates, including several types of monkeys as well as baboons, with either culture-adapted simian (SA11) or human (Wa) rotavirus or fecal preparations of human rotaviruses, will cause diarrheal illness in most animals during their first week of life (21,23,26,31,36,41,55). However, after that time, essentially no illness was observed, and most of the older animals neither shed virus nor seroconverted.…”