Group A rotavirus infection and age-dependent diarrheal disease in rats: Anew animal model to study the pathophysiology of rotavirus infection

Group A rotaviruses are major pathogens causing acute gastroenteritis in ch ildren and animals. To determine if group A rotavirus replicates and induce s disease in rats, antibody-negative Lewis neonatal or adult rats were inoc ulated orally with tissue culture-adapted human (Wa, W161, and HAL1166), si mian (rhesus rotavirus [RRV] and SA11), bovine (WC3), lapine (ALA), or porc ine (OSU) rotavirus strains, wild-type murine (ECwt) rotavirus strain, or p hosphate-buffered saline (PBS). Rotavirus infection in rats was evaluated b y (i) clinical findings, (ii) virus antigen shedding or infectious virus ti ters in the feces or intestinal contents measured by enzyme-linked immunoso rbent assay or fluorescent-focus assay, (iii) histopathological changes in the small intestine, (iv) distribution of rotavirus antigen in small-intest ine sections by immunofluorescence, and (v) growth rate. Rotavirus infectio n of 5-day-old but not greater than or equal to 21-day-old rats resulted in diarrhea that lasted from I to 10 days postinoculation. The severity of di sease and spread of infection to naive littermates differed depending on th e virus strain used for inoculation. The duration of virus antigen shedding following infection was considerably prolonged (up to 10 days) in neonatal rats compared to that in 21-day-old rats (1 or 2 days). Based on lack of v irus antigen shedding and disease induction, the murine ECwt rotavirus was the only strain tested that did not infect rats. Histopathological changes in the small-intestine mucosa of 5-day-old RRV-inoculated rats but not of P BS-inoculated rats was limited to extensive enterocyte vacuolation in the i leum. In RRV-inoculated neonatal rats, rotavirus antigen was detected in th e epithelial cells on the upper half of the intestinal villi of the jejunum and ileum. In addition, infection of neonatal rats with RRV but not with P BS resulted in reduced weight gain. Rats infected with group A rotaviruses provide a new animal model with unique features amenable to investigate rot avirus pathogenesis and the molecular mechanisms of intestinal development, including physiological factors that may regulate age-dependent rotavirus- induced diarrhea.