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Vet Pathol 45:551-562 (2008)
© 2008 American College of Veterinary Pathologists
ANIMAL MODELS OF HUMAN DISEASE

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

J. M. A. van den Brand, B. L. Haagmans, L. Leijten, D. van Riel, B. E. E. Martina, A. D. M. E. Osterhaus and T. Kuiken

Department of Virology, Erasmus Medical Center, Rotterdam, the Netherlands

Abstract

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.

Key words: Angiotensin-converting enzyme (ACE2); cats; coronavirus; ferrets; histology; immunohistochemistry; respiratory system; severe acute respiratory syndrome (SARS).

Request reprints from Dr. Thijs Kuiken, Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, (The Netherlands). E-mail: t.kuiken{at}erasmusmc.nl






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