Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice.
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.
De Albuquerque
Nadine
N
Toronto General Hospital, 585 University Ave., NCSB-11-1236, Toronto, Ontario M5G 2N2, Canada.
Baig
Ehtesham
E
Ma
Xuezhong
X
Zhang
Jianhua
J
He
William
W
Rowe
Andrea
A
Habal
Marlena
M
Liu
Mingfeng
M
Shalev
Itay
I
Downey
Gregory P
GP
Gorczynski
Reginald
R
Butany
Jagdish
J
Leibowitz
Julian
J
Weiss
Susan R
SR
McGilvray
Ian D
ID
Phillips
M James
MJ
Fish
Eleanor N
EN
Levy
Gary A
GA
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
D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D007372:Interferons