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 language | English (US) |
|---|---|
| Pages (from-to) | 286-293 |
| Number of pages | 8 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 190 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Detection of viral infection in the respiratory tract of virus antibody free mice
T2 - Advantages of high-resolution imaging for respiratory toxicology
AU - Phimister, Andrew J.
AU - Day, Kimberly C.
AU - Gunderson, Andrew D.
AU - Wong, Viviana J.
AU - Lawson, Gregory W.
AU - Fanucchi, Michelle V.
AU - Van Winkle, Laura S.
AU - Kendall, Lon V.
AU - Plopper, Charles
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
KW - Histopathology
KW - Membrane permeability
KW - Respiratory viral infection
UR - http://www.scopus.com/inward/record.url?scp=0043093898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0043093898&partnerID=8YFLogxK
U2 - 10.1016/S0041-008X(03)00234-5
DO - 10.1016/S0041-008X(03)00234-5
M3 - Article
C2 - 12902200
AN - SCOPUS:0043093898
VL - 190
SP - 286
EP - 293
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 3
ER -