title: Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice.
abstract: 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 MHV-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.
authors.affiliation: Toronto General Hospital, 585 University Ave., NCSB-11-1236, Toronto, Ontario M5G 2N2, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: De Albuquerque
authors.forename: Ehtesham
authors.initials: E
authors.lastname: Baig
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Ma
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: He
authors.forename: Andrea
authors.initials: A
authors.lastname: Rowe
authors.forename: Marlena
authors.initials: M
authors.lastname: Habal
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Liu
authors.forename: Itay
authors.initials: I
authors.lastname: Shalev
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Downey
authors.forename: Reginald
authors.initials: R
authors.lastname: Gorczynski
authors.forename: Jagdish
authors.initials: J
authors.lastname: Butany
authors.forename: Julian
authors.initials: J
authors.lastname: Leibowitz
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
authors.forename: Ian D
authors.initials: ID
authors.lastname: McGilvray
authors.forename: M James
authors.initials: MJ
authors.lastname: Phillips
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
authors.forename: Gary A
authors.initials: GA
authors.lastname: Levy
mesh_terms: D000818:Animals; D001483:Base Sequence; D018352:Coronavirus Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D006517:Murine hepatitis virus / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013045:Species Specificity
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D007372:Interferons