Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice

被引:123
作者
De Albuquerque, Nadine
Baig, Ehtesham
Ma, Xuezhong
Zhang, Jianhua
He, William
Rowe, Andrea
Habal, Marlena
Liu, Mingfeng
Shalev, Itay
Downey, Gregory P.
Gorczynski, Reginald
Butany, Jagdish
Leibowitz, Julian
Weiss, Susan R.
McGilvray, Ian D.
Phillips, M. James
Fish, Eleanor N.
Levy, Gary A.
机构
[1] Univ Toronto, Univ Hlth Network, Dept Med, Toronto, ON, Canada
[2] Univ Toronto, Univ Hlth Network, Dept Surg, Toronto, ON, Canada
[3] Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada
[4] Univ Toronto, Univ Hlth Network, Multi Organ Transplant Program, Toronto, ON, Canada
[5] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
[6] Texas A&M Univ Syst HSC, Dept Microbial & Mol Pathogenesis, College Stn, TX USA
关键词
D O I
10.1128/JVI.00747-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MRV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.
引用
收藏
页码:10382 / 10394
页数:13
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