A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice

PLoS Pathogens
Anjeanette RobertsKanta Subbarao

Abstract

No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations sugg...Continue Reading

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Citations

Oct 16, 2007·Clinical Microbiology Reviews·Vincent C C ChengKwok Yung Yuen
Sep 27, 2008·Journal of Virology·Eric F DonaldsonRalph S Baric
Nov 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michelle M BeckerMark R Denison
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Jul 19, 2011·Future Virology·Dale L Barnard, Yohichi Kumaki
Sep 18, 2012·Critical Reviews in Microbiology·Derrick LouzRob C Hoeben
Feb 9, 2016·Current Opinion in Virology·Rahul Vijay, Stanley Perlman

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Methods Mentioned

BETA
PCR
X-ray
light microscopy

Software Mentioned

Auto Assembler DNA Sequence Assembly Prism
icSARS

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