Effect of malnutrition on extraintestinal spread of rotavirus and development of hepatitis in mice

Abstract

The effects of malnutrition on the extramucosal spread and severity of the clinical disease were examined in suckling BALB/c mice infected with heterologous rhesus rotavirus (RRV). Control animals were inoculated with homologous murine rotavirus (MRV). Following oral infection with RRV, 100% of malnourished and 90% of normally nourished mice exhibited watery diarrhea within 48 hours. The clinical symptoms appeared more severe and of longer duration in the malnourished group. At 7 to 14 days post-inoculation, 30 of 79 (38%) malnourished and 19 of 92 (21%) well nourished mice developed icterus, clay-colored feces and dark yellow urine. The mortality rates were 9% and 0%, respectively. Light microscopy revealed an acute hepatitis with foci of necrosis. Rotavirus was detected in liver tissue by cell culture infectivity, immunofluorescence assay and electron microscopy. Homologous MRV infection resulted in diarrhea in all animals and with increased severity in the malnourished group. Significantly, however, none of the control animals developed hepatitis and no virus could be detected in the liver. These results suggest that malnutrition may exert significant influence on the severity of rotavirus infection and on the extent of extramucosal spread of RRV. Since several heterologous rotavirus strains are currently being tested in human vaccine trials, the implications of our observations suggest that special attention should be paid to malnourished infants and that screening of hepatic function should be included in vaccine protocols.