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Extramucosal spread and development of hepatitis in immunodeficient and normal mice infected with rhesus rotavirus
I Uhnoo1, M Riepenhoff-Talty, T Dharakul
1Department of Pediatrics, School of Medicine, State University of New York, Buffalo.
Abstract:
The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine strain WC3 or homologous murine rotaviruses. This finding of a novel rotavirus-induced disease manifestation suggests altered tissue tropism in a heterologous host for a group of viruses previously shown to replicate exclusively in the gut mucosa. The implications of our observations suggest that in human vaccine trials utilizing heterologous rotavirus strains, special attention should be paid to children with immunodeficiency disorders, and screening for hepatic function should be included in vaccine protocols.
Insights
Rhesus rotavirus caused hepatitis and liver disease in immunodeficient mice, a novel finding suggesting altered tissue tropism. This highlights the need for careful screening in human vaccine trials, especially for immunocompromised children.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Rotaviruses typically infect the gut mucosa.
- Previous studies focused on homologous murine rotavirus strains.
Purpose of the Study:
- To evaluate the pathogenicity of heterologous animal rotaviruses (rhesus and bovine) in immunocompetent and immunodeficient mice.
- To investigate novel disease manifestations beyond the gut mucosa.
Main Methods:
- Inoculation of SCID mice and BALB/c mice with rhesus rotavirus (MMU 18006), bovine rotavirus (WC3), or murine rotaviruses.
- Clinical observation, mortality assessment, and histopathological examination of liver tissues.
- Detection of rotavirus in liver tissue using cell culture, immunofluorescence, and electron microscopy.
Main Results:
- Rhesus rotavirus caused hepatitis in 84% of SCID mice and 21% of BALB/c mice, with significant mortality in SCID mice.
- SCID mice developed chronic liver disease; BALB/c mice showed transient symptoms.
- Rotavirus was detected in liver tissue of most infected mice, indicating extramucosal spread and hepatitis.
- Bovine and homologous murine rotaviruses did not cause hepatitis or extramucosal spread.
Conclusions:
- Heterologous rhesus rotavirus exhibits altered tissue tropism, causing hepatitis in mice.
- This finding is significant for understanding rotavirus pathogenesis and potential risks in human vaccine trials.
- Immunocompromised individuals may be at higher risk for novel rotavirus-induced diseases.