Rotavirus Infection: Epizootic Diarrhea of Infant Mice

Epizootic diarrhea of infant mice (EDIM) virus belongs to the family Reoviridae, genus Rotavirus. The rotavirus A group encompasses viruses of humans, nonhuman pri­mates, cattle, sheep, horses, pigs, dogs, cats, turkeys, chickens, and rabbits that are closely related genetically and antigenically.

Epizootiology and Pathogenesis

EDIM virus is highly contagious and prevalent in both laboratory and wild mice. Disease manifestations are relatively rare once infection is enzootic, due to protec­tion of clinically susceptible infant mice by maternal IgA. Typically, clinical signs of EDIM occur in naive breeding populations, but once infection is enzootic within the colony, EDIM disease is no longer apparent, although EDIM virus remains. Rotaviruses are shed copi­ously in feces, and transmission is by the orofecal route. Clinical disease ranges from inapparent to severe, depending primarily upon age. All ages of mice are susceptible to infection; however, disease is limited to mice less than 2 weeks of age. Virus selectively infects terminally differentiated enterocytes of villi and surface mucosa of the small and large intestine, respectively. These cells are most plentiful and widespread in the neonatal bowel and diminish in number, distribution, and degree of terminal differentiation as mucosal pro­liferative kinetics accelerate with acquisition of intesti­nal microflora.

During the first few days of infection, there is fluid accumulation and dilation of the small intestine. Diar­rhea is induced by a combination of factors, including apoptosis and loss of absorptive epithelium, replace­ment of lost cells with immature nonabsorptive cells, altered carbohydrate absorption, osmotic effects related to luminal carbohydrate and bacterial fermentation, and active secretion of fluid and electrolytes. The secretory

FIG. 1.42. Infant mouse with epizootic diarrhea of infant mice (EDIM), caused by rotavirus. Note the full stomach, the flaccid and dilated small intestine, and pasting of the tail base with soft feces.

stimulus appears to be mediated by an enterotoxic effect of the viral nonstructural protein 4, which can be evoked with inactivated virus or recombinant protein, and acti­vation of the enteric nervous system. Overgrowth of E. coli, and its atypical abundance in the upper small intestine, accompany the malabsorptive effects of the virus.

Pathology

Infection is often silent, but clinically affected mice can be runted and potbellied, with loose, mustard-colored feces staining the perineum.

Diagnosis

EDIM can be diagnosed presumptively on the basis of age, clinical signs, and lesions. Differential diagnoses include enterotropic MHV, MAdV-2, reovirus, salmonel­losis, Tyzzer's disease, and Clostridial enteropathy. Vac­uolation and intracytoplasmic inclusions must be differentiated from absorption vacuoles of the neonatal

FIG. 1.43. Small intestine of an infant mouse infected with rotavirus. Note the cytoplasmic swelling of enterocytes at the tips of the villi. Microscopic lesions are often subtle and may not be readily apparent.

apical tubular system that occur in the distal small intestine, which may contain solitary eosinophilic glob­ules. Definitive diagnosis can be achieved by electron microscopy of intestinal mucosa or feces. Rotavirus anti­gen can be detected in feces by ELISA, and RNA can be detected by PCR. Antigen detection can be accomplished with commercially available rotavirus diagnostic kits, but false-positive reactions can occur with certain mouse diets. Careful controls are therefore advised. Serology for EDIM virus antibody is useful for surveillance and retro­spective confirmation of infection.