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

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^*

来源：Journal of Virology, 2006, 80(21): 10382-10394.

DOI：10.1128/JVI.00747-06

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.

• 出版日期2006-11