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Published online ahead of print on 9 September 2009 as doi:10.1099/vir.0.014282-0
Journal of General Virology 2009;90:2956.

A more recent version of this article appeared on December 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.014282-0
© 2009 Society for General Microbiology

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Rat respiratory coronavirus infection: Replication in airway and alveolar epithelial cells and innate immune response

C. Joel Funk1, Rizwan Manzer1, Tanya Miura2, Steve D. Groshong1, Yoko Ito1, Emily Travanty1, Jennifer Leete1, Kathryn Holmes3 and Robert J. Mason1,4

1 National Jewish Health;
2 University of Idaho;
3 University of Colorado Denver Health Sciences Center

4 E-mail: masonb{at}njhealth.org

The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6-8 week old Fischer 344 rats. SDAV inoculation produced a 7% body weight loss over a 5-day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 after inoculation. Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45% compared to 6% of the cells in control samples on day 2 after mock inoculation (p.i.). Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on day 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX, and CINC-1 in BALF increased on day 4 after inoculation, but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural host of the virus.

Received 18 June 2009; accepted 2 September 2009.





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