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

J Gen Virol. 2009 Dec;90(Pt 12):2956-2964. doi: 10.1099/vir.0.014282-0. Epub 2009 Sep 9.

Abstract

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 post-inoculation (p.i.). 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 with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 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 p.i., 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 virus host.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / physiopathology
  • Coronavirus Infections* / virology
  • Coronavirus, Rat / pathogenicity*
  • Coronavirus, Rat / physiology
  • Cytokines / metabolism
  • Epithelial Cells / virology*
  • Immunity, Innate
  • Lung / cytology
  • Lung / virology*
  • Male
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / virology*
  • Pulmonary Surfactants / metabolism
  • Rats
  • Rats, Inbred F344
  • Virus Replication*
  • Weight Loss

Substances

  • Cytokines
  • Pulmonary Surfactants