Effect of nutritional deprivation on mucosal viral infections

Suckling BALB-c mice, subjected to nutritional deprivation in artificially expanded litters (18 to 20 pups), were compared to normally nourished pups (7-9 per litter) in a series of experiments designed to provide data on morphologic and functional alterations of the small intestine during malnutrition and infection. The effects of protein calorie malnutrition (PCM) on the viral replication pattern and severity of clinical disease were examined in suckling mice infected with murine rotavirus (MRV). The infection in nutritionally deprived animals was characterized by a significant decrease in the minimal infectious dose and in the incubation period for the onset of diarrhea as well as increased severity of disease when compared to well nourished controls. Rotavirus-specific antibody, administered orally prior to virus inoculation, significantly reduced MRV replication in both groups but most strikingly in malnourished animals. Additional studies of the uptake of a macromolecule [ovalbumin (OVA)] following oral administration to experimental and control groups showed more rapid and complete absorption in the malnourished animals. Infection further enhanced the uptake of OVA, suggesting that both PCM and rotavirus infection alter the permeability of the small intestine. An unexpected observation of rotavirus-associated hepatitis in CB-17scid mice was also made in nearly 40% of malnourished mice inoculated with 10(6) PFU of Rhesus rotavirus (RRV). Mice with PCM exhibited a susceptibility to hepatitis between SCID mice (80%) and immunologically normal mice (18%). While these data are not sufficient to confirm a nutritionally-mediated immunoincompetence, they do suggest that either loss of immune competence and/or increased gut permeability in malnourished animals may allow a more severe homologous rotavirus infection as well as extraintestinal spread of heterologous rotavirus.