Pathology of immunodeficient mice with naturally occurring murine norovirus infection

Jerrold M Ward1, Christiane E Wobus, Larissa B Thackray

  • 1Infectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, NIAID, NIH, Twinbrook III, Bethesda, Maryland 20892-8135, USA. jeward@mail.nih.gov

Toxicologic Pathology
|November 1, 2006
PubMed

Insights

Murine norovirus (MNV) can cause disseminated infections with inflammation in multiple organs in certain immunodeficient mice. Further research is needed to understand its impact on research studies involving these mice.

Area of Science:

  • Veterinary Pathology
  • Immunology
  • Virology

Background:

  • Murine norovirus (MNV) is a recently discovered virus with limited known epidemiology and natural history.
  • MNV was identified in immunodeficient mice (Rag2-/-/Stat1-/-) in a U.S. research facility.
  • Sentinel mice in holding rooms showed MNV-specific antibodies, prompting further investigation.

Purpose of the Study:

  • To investigate the pathology of naturally occurring MNV infection in various immunodeficient mouse models.
  • To characterize the clinical manifestations and tissue tropism of MNV in susceptible mouse lines.
  • To assess the potential confounding effects of MNV on research studies.

Main Methods:

  • Studied naturally occurring MNV infection in 28 immunodeficient mice across five genotypes (Rag1-/-/IFNgamma R-/-, OT1 Rag1-/-/IFNgamma R-/-, OT2 Rag1-/-/IFNgamma R-/-, Rag1-/-/Stat1-/-, and Rag2-/-).
  • Mice were housed in two U.S. research facilities where sentinel mice had tested positive for MNV antibodies.
  • Pathological examination of infected tissues was performed.

Main Results:

  • MNV established disseminated infections in certain immunodeficient mouse lines.
  • Characteristic inflammation was observed in the liver (hepatitis), lungs (focal interstitial pneumonia), and body cavities (peritoneal and pleural).
  • Asymptomatic MNV infection occurred in the mesenteric lymph nodes of Rag2-/- mice.

Conclusions:

  • MNV can cause significant pathology, including hepatitis and pneumonia, in specific immunodeficient mouse models.
  • Asymptomatic infection is possible, highlighting the need for careful monitoring.
  • The potential for MNV to confound immunological, toxicological, and pathological research requires further investigation.

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