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

Andrew J. Phimister, Kimberly C. Day, Andrew D. Gunderson, Viviana J. Wong, Gregory W. Lawson, Michelle V. Fanucchi, Laura S. Van Winkle, Lon V. Kendall, Charles Plopper

Research output: Contribution to journalArticle

2 Citations (Scopus)

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-μm 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.

Original languageEnglish (US)
Pages (from-to)286-293
Number of pages8
JournalToxicology and Applied Pharmacology
Volume190
Issue number3
DOIs
StatePublished - Aug 1 2003

Fingerprint

Virus Diseases
Viruses
Respiratory System
Toxicology
Assays
Animals
Imaging techniques
Lung
Antibodies
Respiratory system
Epoxy Resins
Membranes
Wounds and Injuries
Pathology
Pathogens
Cell membranes
Infiltration
Paraffin
Transmission Electron Microscopy
Virion

Keywords

  • Histopathology
  • Membrane permeability
  • Respiratory viral infection

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Detection of viral infection in the respiratory tract of virus antibody free mice : Advantages of high-resolution imaging for respiratory toxicology. / Phimister, Andrew J.; Day, Kimberly C.; Gunderson, Andrew D.; Wong, Viviana J.; Lawson, Gregory W.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Kendall, Lon V.; Plopper, Charles.

In: Toxicology and Applied Pharmacology, Vol. 190, No. 3, 01.08.2003, p. 286-293.

Research output: Contribution to journalArticle

Phimister, Andrew J. ; Day, Kimberly C. ; Gunderson, Andrew D. ; Wong, Viviana J. ; Lawson, Gregory W. ; Fanucchi, Michelle V. ; Van Winkle, Laura S. ; Kendall, Lon V. ; Plopper, Charles. / Detection of viral infection in the respiratory tract of virus antibody free mice : Advantages of high-resolution imaging for respiratory toxicology. In: Toxicology and Applied Pharmacology. 2003 ; Vol. 190, No. 3. pp. 286-293.
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