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Experimental murine cytomegalovirus infection in severe combined immunodeficient mice
R P Reynolds1, R J Rahija, D I Schenkman
1Duke University Medical Center, Duke University, Durham, NC 27710.
Abstract:
Severe combined immunodeficient (scid) and BALB/c mice were experimentally infected with murine cytomegalovirus (MCMV). Scid mice infected by the intraperitoneal route died or were moribund at dose-dependent times ranging from 12 to 13 days after inoculation for > or = 3.00 x 10(4) plaque forming units (pfu) of virus to 25 days for 1.17 x 10(2) pfu. Histologic lesions included severe adrenal necrosis at low doses and splenic necrosis at high doses. Multinucleate hepatocytes with multiple inclusion bodies were observed at all doses. In visceral organs, the inflammatory response consisted of cell necrosis and neutrophil infiltration. Scid mice infected with 1.00 x 10(3) pfu by the intranasal route were moribund by 24 or 25 days after inoculation. Viral titers in tissues examined from these mice increased in all organs examined until they became moribund. BALB/c mice infected intranasally had detectable virus titers in the adrenal glands, salivary glands, lungs, and spleen by 7 or 14 days after inoculation, but decreased thereafter. These mice remained clinically normal through the infection. In BALB/c mice, histologic lesions were present only in the salivary glands.
Insights
Severe combined immunodeficient (scid) mice infected with murine cytomegalovirus (MCMV) experienced dose-dependent mortality and severe organ damage. In contrast, immunocompetent BALB/c mice showed milder, transient effects, highlighting MCMV
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Murine cytomegalovirus (MCMV) is a common pathogen with varying effects depending on host immunity.
- Severe combined immunodeficient (scid) mice lack functional T and B lymphocytes, making them highly susceptible to infections.
- BALB/c mice are immunocompetent and serve as a standard model for studying viral infections in normal hosts.
Purpose of the Study:
- To investigate the pathogenesis of murine cytomegalovirus (MCMV) infection in severe combined immunodeficient (scid) mice compared to immunocompetent BALB/c mice.
- To characterize the dose-dependent effects of MCMV infection, including mortality, viral titers, and histological lesions.
- To understand the immune response differences between scid and BALB/c mice following MCMV challenge.
Main Methods:
- Experimental infection of scid and BALB/c mice with different doses of MCMV via intraperitoneal and intranasal routes.
- Monitoring of survival rates and clinical signs post-infection.
- Histopathological examination of visceral organs to identify lesions and viral inclusion bodies.
- Quantification of viral titers in various tissues.
Main Results:
- Scid mice exhibited dose-dependent mortality, with death occurring between 12-25 days post-infection.
- Histological analysis of scid mice revealed severe adrenal and splenic necrosis, multinucleated hepatocytes with inclusion bodies, and inflammatory infiltrates.
- BALB/c mice showed transient viral presence in adrenal, salivary glands, lungs, and spleen, with minimal clinical signs and only salivary gland lesions.
Conclusions:
- MCMV infection is rapidly lethal in scid mice, causing widespread organ damage, underscoring the critical role of adaptive immunity in controlling MCMV.
- BALB/c mice effectively control MCMV replication, demonstrating a robust immune response that limits pathology to minor salivary gland lesions.
- This study provides insights into MCMV pathogenesis and the differential susceptibility of immunodeficient versus immunocompetent hosts.