Development of a murine model to study the pathogenesis of rotavirus infection

Abstract

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.

Characterization of a Novel G3P[3] Rotavirus Isolated from a Lesser Horseshoe Bat: a Distant Relative of Feline/Canine Rotaviruses

“…Ijaz et al used suckling mice to compare the virulence of bovine RVA (BRV) and murine RVA (MRV) and found that an inoculation dose as low as 100 PFU/mouse of BRV and 10 PFU/mouse of MRV could induce disease in mice (47). In consideration of animal welfare, the 50% lethal dose of MSLH14 was not determined but a preliminary animal test showed that a dose as low as 5 ϫ 10 2 TCID 50 of virus could induce rapid infection of suckling mice with 100% mortality.…”

Llama-Derived Single-Chain Antibody Fragments Directed to Rotavirus VP6 Protein Possess Broad Neutralizing Activity In Vitro and Confer Protection against Diarrhea in Mice

“…The pups were challenged either with BRV C486 or murine RV EC w . Pup challenge conditions for both strains were standardized in order to produce diarrhea in 100% of the nontreated control pups similarly to a previous report (26,36). On day 1, at 2 h after the VHH administration pups received 20 l of 5% bicarbonate solution, they were also challenged by the intragastric route with 100 l of BRV C486 containing a total of 30 times the dose that caused diarrhea in 50% of suckling mice (DD 50 ) (6 ϫ 10 5 FFU/mouse) (experiment A) or with 100 l of murine RV EC w containing 316 DD 50 (experiment B).…”

Characterization of Vp4 and Vp7 of a Murine Rotavirus (Yr-1) Isolated in Japan

“…Not only homologous rotaviruses such as EW, ER and YR-1, but also heterologous strains such as SA11 (G3), MO (G3) and a vaccine candidate strain (e.g., RRV, G3) cause gastroenteritis in newborn mice (6)(7)(8)(9). The conventional method of serotyping is the plaque-or focus-reduction neutralization assay.…”

“…Passive immune prophylaxis of rotavirus gastroenteritis was proved to be feasible in suckling mice and infants with lyophilized colostral milk from human rotavirus-immunized cows (6). For experiments with active and passive immunity against rotavirus gastroenteritis, a murine model has been employed by using either homologous or heterologous rotaviruses (6)(7)(8)(9). Epizootic diarrhea of newborn mice, YR-1, was observed in Japan in 1974 (10).…”