Histologic Lesions Induced by Murine Norovirus Infection in Laboratory Mice

Abstract

Murine noroviruses (MNV) are highly prevalent in laboratory mice, can cause persistent infections, and have been shown to infect macrophages, dendritic cells, and B cells. To address the potential impact of MNV infection on research outcomes, numerous studies have been conducted with various mouse models of human disease and have generated mixed results ranging from no impact to significant disease. Many of these studies included histologic evaluations after MNV infection, and similarly these results have been variable as to whether MNV induces lesions despite the fact that localization of MNV by viral culture and molecular techniques have demonstrated systemic distribution regardless of mouse immune status. The aim of this review is to summarize the histologic findings that have been reported with MNV infection in several mouse models. The studies demonstrate that experimental infection of MNV in wild-type mice results in minimal to no histologic changes. In contrast, immunodeficient mice consistently have detectable MNV-induced lesions that are typically inflammatory and, in the most severe cases, accompanied by necrosis. In these, the liver is commonly affected with more variable lesions reported in the lung, gastrointestinal tract, mesenteric lymph nodes, brain, and spleen. In specific disease models including atherosclerosis, MNV infection had a variable impact that was dependent upon the mouse model, viral strain, timing of infection, or other experimental variables. It is important to recognize the reported MNV lesions to help discern the possible influence of MNV infection on data generated in mouse models.

A Narrative Review of Norovirus Gastroenteritis: More Global Attention Is Needed

“…To date, most of the data on NoV comes from the study of surrogates, such as MNV, feline calicivirus (FCV), and Tulane virus (TV). [26][27][28] MNV has become the most frequently used NoV surrogate as it is the only NoV with a cell culture system and small animal model. TV also has broad uses as a surrogate since it has similar genetic identity to NoVs and recognizes histoblood group antigens (HBGA).…”

Authors’ Response

“…We appreciate Dr Van Kruiningen's attention to our review article, 3 his comments regarding the characterization of crypt abscesses, and the opportunity to present additional images that reflect the full spectrum of crypt and mucosal changes noted in the in the FVB.129P2-Abcb1a tm1Bor (Mdr1a-/-Taconic Biosciences, Hudson, NY) model (originally reported in Lencioni et al 4 ). We agree that the crypt figure initially published in 2008 is not a ''bona fide'' crypt abscess, as defined in human gastrointestinal pathology and noted by Van Kruiningen.…”

“…Figure 1. This is the original image published in Lencioni et al 4 and Hsu et al 3 Hematoxylin and eosin (HE). Figure 5; the boxed area is magnified in Figure 6.…”

Effects of Pelleting, Irradiation, and Autoclaving of Rodent Feed on MPV and MNV Infectivity

“…9,28,51 Although MNV may cause lethal infection in severely immunodeficient mice, 31 clinical signs are generally absent in immune-competent mice. 24 Nonetheless, MNV has been shown to infect macrophages, dendritic cells, and B cells and is therefore likely to interfere with immunologic and inflammatory studies. 24 MPV likewise causes asymptomatic infection in mice but has a propensity to infect lymphoid tissues and may interfere with research through its effects on the host immune response.…”

“…24 Nonetheless, MNV has been shown to infect macrophages, dendritic cells, and B cells and is therefore likely to interfere with immunologic and inflammatory studies. 24 MPV likewise causes asymptomatic infection in mice but has a propensity to infect lymphoid tissues and may interfere with research through its effects on the host immune response. 35 As such, both viruses are often excluded from barrier facilities but yet remain prevalent in research colonies.…”