Pathology of experimental SARS coronavirus infection in cats and ferrets.
The pathology of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV, in the respiratory tracts of these species is unknown. We observed SARS-CoV antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ACE2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. All infected cats and ferrets had diffuse alveolar damage associated with SARS-CoV antigen expression. A novel SARS-CoV-associated lesion was tracheo-bronchoadenitis in cats. SARS-CoV antigen expression occurred mainly in type I and II pneumocytes and serous cells of tracheo-bronchial submucosal glands of cats and in type II pneumocytes of ferrets. ACE2 expression occurred mainly in type I and II pneumocytes, tracheo-bronchial goblet cells, serous epithelial cells of tracheo-bronchial submucosal glands in cats, and type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets. In conclusion, the pathology of SARS-CoV infection in cats and ferrets resembles that in humans except that syncytia and hyaline membranes were not observed. The identification of tracheo-bronchoadenitis in cats has potential implications for SARS pathogenesis and SARS-CoV excretion. Finally, these results show the importance of ACE2 expression for SARS-CoV infection in vivo: whereas ACE2 expression in type I and II pneumocytes in cats corresponded to SARS-CoV antigen expression in both cell types, expression of both ACE2 and SARS-CoV antigen in ferrets was limited mainly to type II pneumocytes.
van den Brand
J M A
JM
Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Haagmans
B L
BL
Leijten
L
L
van Riel
D
D
Martina
B E E
BE
Osterhaus
A D M E
AD
Kuiken
T
T
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D002415:Cats / Q000821:virology*; D004195:Disease Models, Animal; D005289:Ferrets / Q000821:virology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000254:growth & development*; D045169:Severe Acute Respiratory Syndrome / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D013047:Specific Pathogen-Free Organisms
D000956:Antigens, Viral; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2