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Detection of viral infection in the respiratory tract of virus antibody free mice: advantages of high-resolution imaging for respiratory toxicology.

Abstract：

:Using a highly sensitive membrane permeability assay, a viral infection was discovered in the lungs of virus antibody free (VAF) Swiss-Webster mice purchased for respiratory toxicology studies. The assay is based on the uptake of a charged fluorescent compound by cells lacking an intact plasma membrane. Lungs from 74% of the untreated animals from a single vendor tested positive for injury in this assay. High-resolution histopathologic analysis of 1-microm epoxy resin sections from affected animals identified increased peribronchiolar lymphocytic infiltration and markers of epithelial cell injury. Viral particles were directly observed to be budding from the membranes of infiltrating lymphocytic cells by transmission electron microscopy. Standard histological analysis of paraffin-embedded tissues from lungs of the same mice failed to detect obvious pathology. Serological analyses failed to detect the presence of a virus in the affected mice. Therefore, we conclude that (1) a pathogenic condition was present in the respiratory systems of mice judged pathogen free by standard methodologies, (2) the observed condition produced a pattern of injury comparable to those caused by pulmonary toxicants, (3) high-resolution histopathology and advanced imaging techniques can increase the potential for detection of pathological conditions, and (4) apparently healthy animals can have unrecognized infections with the potential for confounding respiratory toxicology studies.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Phimister AJ,Day KC,Gunderson AD,Wong VJ,Lawson GW,Fanucchi MV,Van Winkle LS,Kendall LV,Plopper CG

doi

10.1016/s0041-008x(03)00234-5

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

286-93

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041008X03002345

journal_volume

190

pub_type

杂志文章

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