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Pathology of Immunodeficient Mice With Naturally Occurring Murine Norovirus Infection

¹ Comparative Medicine Branch and
² Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland 20892-8135, USA
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

Correspondence: Address correspondence to: Dr. Jerrold M. Ward, Infectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, NIAID, NIH, Twinbrook III, Room 2W-01A, MSC 8135, Bethesda, MD 20892-8135, USA; e-mail:jeward{at}mail.nih.gov

Murine norovirus (MNV) was recently discovered in Rag2^–/–/Stat1^–/– mice in a U.S. medical research facility. Presently, little is known concerning the epidemiology and natural history of this virus. We studied the pathology of naturally occurring MNV infection in 28 immunodeficient mice of several different genotypes (Rag1^–/–/IFN R^–/–, OT1 Rag1^–/–/IFN R^–/–, OT2 Rag1^–/–/IFN R^–/–, Rag1^–/–/Stat1^–/–, and Rag2^–/–) that were maintained in two U.S. research facilities. The mice were selected for study because sentinel mice housed in their holding rooms had been identified as positive for MNV-specific antibodies during routine screening for infectious agents. Our data indicate that in certain lines of immunodeficient mice, MNV can establish a disseminated infection that is characteristically associated with inflammation in multiple tissues, including liver (hepatitis), lung (focal interstitial pneumonia) and the peritoneal and pleural cavities. In addition, MNV can establish an asymptomatic infection in the mesenteric lymph nodes of Rag2^–/– mice. Further studies are needed to determine whether MNV presents a confounding variable in immunological, toxicological and pathological studies in mice naturally infected with MNV.

[The supplemental data referenced in this paper is not printed in this issue of Toxicologic Pathology. It is available as a downloadable file in the online edition of Toxicologic Pathology, 34(6). In order to access the full article online, you must have either an individual subscription or a member subscription accessed through www.toxpath.org.]

Key Words: Hepatitis • murine norovirus • immunodeficient mice • dendritic cells • caliciviruses • pneumonia

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