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A murine model to study enteritis induced by bovine (BRV) and murine rotavirus (MRV) has been developed. The course of infection was determined by clinical symptoms of diarrhea and virus isolation as well as histopathological, immunohistochemical, and electron microscopic methods. Both isolates were able to replicate and produce clinical symptoms in neonatal mice. Rotavirus-free neonates were orally inoculated with MRV or BRV and observed over a 192-hr postinoculation (HPI) period. Following infection with 10(4) PFU of virus, diarrhea and maximal intestinal dysfunction, as measured by xylose absorption, did not occur until beyond 20 hr postinfection even though maximal virus production occurred at 10-15 HPI. Immunohistochemically and by electron microscopy we were able to demonstrate viral antigen and virus particles in the enterocytes of villous tips at 5-8 HPI. The appearance of diarrheal symptoms was dependent on the virus dose and the type of virus isolate inoculated. The disease could be induced with doses as low as 1 x 10(2) PFU/mouse of BRV and 1 x 10(1) PFU/mouse of MRV. On the basis of these results, MRV was found to be more virulent than BRV in this model. The model should prove useful for studies designed to assess rotavirus virulence genes and for vaccine protection studies. This work emphasizes the need for early sample collection for critical evaluation of any vaccine or antiviral agent using this model.

SUMMARYExamples exist in the literature that demonstrate that treatment with immunostimulatory cytosine±phosphate±guanosine (CpG)-DNA can protect mice against infection by intracellular pathogens. There are, however, few studies reporting that CpG-DNA offers similar disease protection in other species. In this study, we assessed the potential of a class A and class B CpG oligodeoxynucleotide (ODN) to induce innate immune responses in sheep, an outbred species. Using peripheral blood mononuclear cells, we have for the ®rst time demonstrated CpG-ODN-induced innate immune responses, including natural-killer-like activity [nonmajor histocompatibility complex (MHC)-restricted cytotoxicity], interferon-a secretion and 2H -5 H A oligoadenylate synthetase activity, that could contribute to immune protection in sheep. The type and magnitude of these responses were dependent on ODN class and non-MHC-restricted killing was not associated with interferon-g production. The latter observation is in contrast with observations reported for mice and humans. These observations support the conclusion that differences in CpG-ODN-induced responses exist among species and that speci®c ODN sequences can signi®cantly in¯uence innate immune responses.

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