title: Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response.
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.
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: C Joel
authors.initials: CJ
authors.lastname: Funk
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Manzer
authors.affiliation: Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844, USA.
authors.forename: Tanya A
authors.initials: TA
authors.lastname: Miura
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Steve D
authors.initials: SD
authors.lastname: Groshong
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Travanty
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Leete
authors.affiliation: Department of Microbiology, University of Colorado Denver, Aurora, CO 80110, USA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Holmes
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D017941:Coronavirus, Rat / Q000472:pathogenicity* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology*; D007113:Immunity, Innate; D008168:Lung / Q000166:cytology / Q000821:virology*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000821:virology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014779:Virus Replication; D015431:Weight Loss
chemical_list: D016207:Cytokines; D011663:Pulmonary Surfactants