Mouse Viruses
Rotavirus (EDIM virus) Sheridan and Vonderfecht, 1986
Etiology.
Rotaviruses are double-stranded, segmented RNA viruses that have a wheel-like ultra structural appearance. EDIM virus is a group A rotavirus that replicates in differentiated epithelial cells of the small intestine by budding into cisternae of endoplasmic reticulum. Currently, only a single antigenic strain is recognized, but antigenically distinct variants may exist. EDIM virus shares an inner capsid antigen with rotaviruses of rabbits, fowl, nonhuman primates, human beings, and domestic and companion animals. These agents tend to be species-specific under natural conditions and can be differentiated by serum neutralization tests. Cultivation of EDIM virus requires the presence of proteolytic enzymes to cleave an outer capsid polypeptide.
Clinical signs.
Clinical signs occur in infant mice less than 2 weeks old. This age-related susceptibility also applies to infection in immunodeficient mice. Furthermore, clinical signs occur only in offspring of non-immune dams, because maternal immunity protects infants until they have outgrown susceptibility to clinical disease (Rose et al., 1998). The cardinal signs are diarrhea with fecal soiling of the perineum, which may extend to the entire pelage in severe cases. Despite high morbidity, mortality is low because affected mice continue to nurse. Transient weight loss does occur, and there may be delay in reaching adult weight. Recovery from infection usually occurs in about 2 weeks and, once weight is regained is clinically complete.
Epizootiology.
EDIM virus appears to be infectious only for mice and occurs episodically in mouse colonies. However, infection is probably widespread geographically. Its prevalence in mouse colonies in the United States ranges between 5 and 25% according to a recent survey (Jacoby and Lindsey, 1997). All ages and both sexes can be infected, but genetic resistance and susceptibility have not been determined. The virus is highly infectious and is transmitted by the oral-fecal route. Asymptomatically infected adult mice can shed virus in feces for at least 17 days, and interval that may be extended in immunodeficient mice (Riepenhoff-Talty et al., 1995). After oral inoculation, virus is essentially restricted to the gastrointestinal tract, particularly the small and large intestine, although small amounts of virus may be present in liver, spleen, kidney, and blood. Nursing dams can contract infection from their litters. Transplacental transmission has not been demonstrated.
Pathology.
Gross lesions occur primarily in the gastrointestinal tract, but thymic atrophy can result from infection-related stress. The intestine is often distended, flaccid, and filled with gray-green gaseous liquid or mucoid fecal material that soils the pelage. The stomach contains curdled milk, except in terminal cases with anal impaction. Virus preferentially infects terminally differentiated enterocytes in the small and large intestine, which accounts for the age-related susceptibility to disease: the number of such cells decreases as the intestinal tract matures. Characteristic histological lesions are most easily discerned in the small intestine in mice less then 2 weeks old (Little and Shadduck,1987). They consist of increased vacuolation of villar epithelial cells with cytoplasmic swelling, which give villi a clubbed appearance. The vacuoles must be differentiated from normal absorption vacuoles in nursing mice. The lamina propria may be edematous, but necrosis and inflammation are not prevalent.
Diagnosis.
EDIM virus infection is detected serologically by IFA or ELISA (Ferner et al., 1987). Clinical disease is diagnosed from signs and typical histological lesions in the intestine, which can be confirmed by immunohistochemical or ultra structural demonstration of virus in intestine or in intestinal filtrates or smears. Rotavirus antigen can be detected in feces by ELISA, but certain dietary ingredients can cause false-positive reactions. Infection can also be diagnosed by RT-PCR (Wilde et al., 1990).
Differential diagnosis.
EDIM virus infection must be differentiated from other diarrhea diseases of suckling mice such as intestinal corona virus (mouse hepatitis) infection, reovirus 3 infection, TyzzerŐs disease, and salmonellosis. The presence of milk in the stomach can be helpful in differentiating EDIM virus infection from more severe enteric infections, such as those caused by pathogenic corona viruses, during which cessation of nursing often occurs. The possibility of dual infections must also be considered. Thymic necrosis in EDIM virus-infected mice, although nonspecific, must be differentiated from that due to mouse thymic virus (MTV) infection.
Prevention and control.
The spread of EDIM can be controlled effectively by the use of micro barrier cages and good sanitation. Because infection appears to be acute and self-limiting, cessation of breeding for 4-6 weeks to allow immunity to build in adults while preventing access to susceptible neonates also is recommended. Alternatively, litters with diarrhea can be culled, in combination with the use of micro barrier cages. The duration of infection in immunodeficient mice has not been determined, but it is reasonable to assume that chronic infection occurs. Therefore, such animals should be eliminated. Litters from immune dams are more resistant to infection. Prevention of EDIM virus infection depends on maintenance of sanitary barrier housing with adequate serological surveillance.
Research complications.
The research complications of EDIM infection pertain to clinical illness with diarrhea and retarded growth. Transient thymic necrosis may perturb immunological responses.