In vivo tropisms and kinetics of rat theilovirus infection in immunocompetent and immunodeficient rats.

Rat theilovirus (RTV) is a cardiovirus related to Theiler's murine encephalomyelitis virus. While RTV is a prevalent viral pathogen of rats used in biomedical research, the pathogenesis and characterization of RTV infections is not well understood. In the studies reported herein, we used immunohistochemistry to identify viral antigens in enterocytes of the small intestines of Sprague-Dawley (SD) rats. Fecal viral shedding in immunocompromised and immunocompetent rats following oral gavage with RTV1 was high for the first 2 weeks of infection with persistent shedding of high viral loads being observed in immunocompromised nude rats but not in immunocompetent rats. RTV was also detected in mesenteric lymph nodes and spleen of immunocompromised rats but not immunocompetent rats. In addition, the magnitude of serum antibody responses differed between immunocompetent rat strains with Brown Norway and SD rats having a significantly higher antibody response than CD or Fischer 344 rats. These data suggest that RTV1 has a tropism for the epithelial cells of the small intestine, immunocompetent rats have differing serum antibody responses to RTV infection, and sustained fecal shedding and extraintestinal dissemination of RTV1 occurs in rats deficient in T cell-dependent adaptive immunity. RTV infection in immunocompromised and immunocompetent rats has merit as a model for further studies of theilovirus pathogenesis following oral viral exposure.

Evaluation of a commercial colorimetric fecal dipstick assay for the detection of Helicobacter hepaticus infections in laboratory mice.

Mice used in biomedical research typically are tested for the presence of Helicobacter spp., including Helicobacter hepaticus. Here we evaluated the ability of a commercially available colorimetric Helicobacter dipstick assay to detect H. hepaticus in experimentally and naturally infected mice, with use of a Helicobacter PCR assay as the 'gold standard' test. None of the fecal samples from experimentally infected A/JCr mice (n = 12) tested positive for Helicobacter by the colorimetric dipstick test. In naturally infected A/JCr and C57BL/6 mice, 11% (1 of 9) and 30% (3 of 10) of fecal samples, respectively, tested positive for Helicobacter by the colorimetric dipstick assay. In these 3 groups of H. hepaticus-infected mice, statistically fewer mice tested positive by the colorimetric dipstick test than by PCR. The colorimetric Helicobacter dipstick assay had an overall diagnostic sensitivity of 13%, diagnostic specificity of 94%, and analytical sensitivity of 10(8) H. hepaticus cfu/mL. As currently formulated, the colorimetric dipstick assay had high specificity but lacked sensitivity for detecting H. hepaticus infections in 2 strains of mice commonly used in research, thereby limiting its utility as a diagnostic screening test for H. hepaticus infections in research mice.

Differential susceptibility of SD and CD rats to a novel rat theilovirus.

Antibodies to rat theilovirus (RTV) have been detected in rats for many years because of their serologic crossreactivity with strains of Theiler murine encephalomyelitis virus (TMEV) of mice. Little information exists regarding this pathogen, yet it is among the most common viruses detected in serologic surveys of rats used in research. In the study reported here, a novel isolate of RTV, designated RTV1, was cultured from the feces of infected rats. The RTV1 genome contained 8094 nucleotides and had approximately 95% identity with another rat theilovirus, NSG910, and 73% identity with TMEV strains. In addition, the genome size of RTV1 was similar to those of TMEV strains but larger than that reported for NSG910. Oral inoculation of Sprague-Dawley (SD) and CD male rats (n = 10 each group) with RTV1 revealed that SD rats were more susceptible than CD rats to RTV1 infection. At 14 d postinoculation, 100% of SD rats shed virus in the feces, and 70% were positive for RTV serum antibodies. By 56 d postinoculation 30% of SD rats continued to have detectable virus in the feces, and 90% had seroconverted. In contrast, in inoculated CD rats RTV was detected only in the feces at 14 d postinoculation, at which time 40% of CD rats were fecal positive. By 56 d postinoculation only 20% of CD rats had detectable RTV serum antibodies. Our data provide additional sequence information regarding a rat-specific Cardiovirus and indicate that SD rats are more susceptible than CD rats to RTV1 infection.