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Kinetics, tissue specificity and pathological changes in murine rotavirus infection of mice
Abstract:
Mice that did not contain antibodies to rotavirus were orally infected with murine rotavirus (EDIM strain) and observed over 7 days. As judged by ELISA, only the small intestine was infected, not the colon. The infection was biphasic, viral antigen peaks being observed at 48 h and approximately 120 h post-infection. Clinically evident diarrhoea was maximal at 72 h. Virus in the upper, middle and lower regions of the small intestine was mainly tissue-associated; most virus was found in the middle small intestine. Two peaks (48 h and 120 h post-infection) of virus antigen were observed in the colon, but these corresponded to luminal, not tissue-associated viral antigen. Only enterocytes in the upper two-thirds of villus epithelia were infected as judged by fluorescent-antibody analysis and transmission electron microscopy. Scanning electron microscopy revealed morphological appearances not hitherto correlated with the progress of the infection: villus tips were convoluted, corresponding to the shedding of virus-infected cells but the lower regions of infected villi were shrunken and considerably narrowed compared to tips.
Insights
Murine rotavirus (EDIM strain) infection in mice primarily targets the small intestine, showing biphasic viral antigen peaks and distinct tissue-associated and luminal viral presence. Diarrhea symptoms peaked at 72 hours post-infection.
Area of Science:
- Virology
- Gastroenterology
- Immunology
Background:
- Rotavirus infections are a significant cause of gastroenteritis in young mammals.
- Understanding the pathogenesis of murine rotavirus (EDIM strain) is crucial for developing effective countermeasures.
- Previous studies have not fully elucidated the tissue tropism and temporal dynamics of EDIM strain infection.
Purpose of the Study:
- To investigate the tissue distribution and temporal progression of murine rotavirus (EDIM strain) infection in mice.
- To characterize the nature of viral antigen presence (tissue-associated vs. luminal) in different intestinal segments.
- To correlate viral infection with observed clinical signs and morphological changes in the small intestine.
Main Methods:
- Oral infection of antibody-negative mice with murine rotavirus (EDIM strain).
- Observation over a 7-day period with daily assessments.
- Enzyme-linked immunosorbent assay (ELISA) for viral antigen detection.
- Fluorescent-antibody analysis and transmission electron microscopy (TEM) for cellular localization.
- Scanning electron microscopy (SEM) for morphological analysis.
Main Results:
- Infection was confined to the small intestine, with no detectable colon infection by ELISA.
- Viral antigen exhibited biphasic peaks at 48 and 120 hours post-infection.
- Tissue-associated virus was predominant in the small intestine, particularly the middle region.
- Colon viral antigen was luminal, not tissue-associated.
- Enterocytes in the upper two-thirds of villi were infected; SEM revealed convoluted villus tips and shrunken lower villi.
Conclusions:
- Murine rotavirus (EDIM strain) exhibits specific tropism for small intestinal enterocytes.
- The biphasic antigen peaks and distinct luminal/tissue association in different gut regions highlight complex infection dynamics.
- Observed morphological changes in villi correlate with cellular infection and shedding, contributing to disease progression.