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Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice.
J Immunol. 2004 Sep 15; 173(6):4030-9.JI

Abstract

We describe a model of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in C57BL/6 mice. A clinical isolate of the virus introduced intranasally replicated transiently to high levels in the lungs of these mice, with a peak on day 3 and clearance by day 9 postinfection. Viral RNA localized to bronchial and bronchiolar epithelium. Expression of mRNA for angiotensin converting enzyme 2, the SARS-CoV receptor, was detected in the lung following infection. The virus induced production in the lung of the proinflammatory chemokines CCL2, CCL3, CCL5, CXCL9, and CXCL10 with differential kinetics. The receptors for these chemokines were also detected. Most impressively, mRNA for CXCR3, the receptor for CXCL9 and CXCL10, was massively up-regulated in the lungs of SARS-CoV-infected mice. Surprisingly Th1 (and Th2) cytokines were not detectable, and there was little local accumulation of leukocytes and no obvious clinical signs of pulmonary dysfunction. Moreover, beige, CD1-/-, and RAG1-/- mice cleared the virus normally. Infection spread to the brain as it was cleared from the lung, again without leukocyte accumulation. Infected mice had a relative failure to thrive, gaining weight significantly more slowly than uninfected mice. These data indicate that C57BL/6 mice support transient nonfatal systemic infection with SARS-CoV in the lung, which is able to disseminate to brain. In this species, proinflammatory chemokines may coordinate a rapid and highly effective innate antiviral response in the lung, but NK cells and adaptive cellular immunity are not required for viral clearance.

Authors+Show Affiliations

Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15356152

Citation

Glass, William G., et al. "Mechanisms of Host Defense Following Severe Acute Respiratory Syndrome-coronavirus (SARS-CoV) Pulmonary Infection of Mice." Journal of Immunology (Baltimore, Md. : 1950), vol. 173, no. 6, 2004, pp. 4030-9.
Glass WG, Subbarao K, Murphy B, et al. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J Immunol. 2004;173(6):4030-9.
Glass, W. G., Subbarao, K., Murphy, B., & Murphy, P. M. (2004). Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. Journal of Immunology (Baltimore, Md. : 1950), 173(6), 4030-9.
Glass WG, et al. Mechanisms of Host Defense Following Severe Acute Respiratory Syndrome-coronavirus (SARS-CoV) Pulmonary Infection of Mice. J Immunol. 2004 Sep 15;173(6):4030-9. PubMed PMID: 15356152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. AU - Glass,William G, AU - Subbarao,Kanta, AU - Murphy,Brian, AU - Murphy,Philip M, PY - 2004/9/10/pubmed PY - 2004/10/20/medline PY - 2004/9/10/entrez SP - 4030 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 173 IS - 6 N2 - We describe a model of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in C57BL/6 mice. A clinical isolate of the virus introduced intranasally replicated transiently to high levels in the lungs of these mice, with a peak on day 3 and clearance by day 9 postinfection. Viral RNA localized to bronchial and bronchiolar epithelium. Expression of mRNA for angiotensin converting enzyme 2, the SARS-CoV receptor, was detected in the lung following infection. The virus induced production in the lung of the proinflammatory chemokines CCL2, CCL3, CCL5, CXCL9, and CXCL10 with differential kinetics. The receptors for these chemokines were also detected. Most impressively, mRNA for CXCR3, the receptor for CXCL9 and CXCL10, was massively up-regulated in the lungs of SARS-CoV-infected mice. Surprisingly Th1 (and Th2) cytokines were not detectable, and there was little local accumulation of leukocytes and no obvious clinical signs of pulmonary dysfunction. Moreover, beige, CD1-/-, and RAG1-/- mice cleared the virus normally. Infection spread to the brain as it was cleared from the lung, again without leukocyte accumulation. Infected mice had a relative failure to thrive, gaining weight significantly more slowly than uninfected mice. These data indicate that C57BL/6 mice support transient nonfatal systemic infection with SARS-CoV in the lung, which is able to disseminate to brain. In this species, proinflammatory chemokines may coordinate a rapid and highly effective innate antiviral response in the lung, but NK cells and adaptive cellular immunity are not required for viral clearance. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/15356152/Mechanisms_of_host_defense_following_severe_acute_respiratory_syndrome_coronavirus__SARS_CoV__pulmonary_infection_of_mice_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15356152 DB - PRIME DP - Unbound Medicine ER -