Vet Pathol. 2008 Jul;45(4):551-62. doi: 10.1354/vp.45-4-551.
Pathology of experimental SARS coronavirus infection in cats and ferrets.
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.
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.
- PMID:
- 18587105
- DOI:
- 10.1354/vp.45-4-551
- [Indexed for MEDLINE]
Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor for the attachment to and uptake of SARS-CoV in host cells.20 The distribution of ACE2 in human tissues corresponds largely to the cell types in which SARS-CoV replication has been observed: in addition to type II pneumocytes and bronchial epithelial cells, ACE2 expression has been observed in type I pneumocytes and endothelial cells as well as smooth muscle cells of blood vessels, but not alveolar macrophages.15,37
Since the appearance of SARS, several animal models have been developed for SARS-CoV infection in humans: SARS-CoV infection in macaques,6 marmosets,10 mice,8,31 golden Syrian hamsters,32 rats,24 cats, and ferrets.22 Subbarao and Roberts35 reviewed the advantages and disadvantages of the above animal models. The limitations of rodents such as hamsters and young inbred mice are that they do not show illness35 and their lung structure differs from that of the human lung;26 the limitations of nonhuman primates are availability, cost, and housing.35 SARS-CoV infections in cats and ferrets do not show these limitations and may therefore be valuable as animal models.
Previous experiments showed that domestic cats and ferrets were susceptible to SARS-CoV infection and that they were able to transmit the virus efficiently to previously uninfected sentinel animals that were housed with them.22 The acute pulmonary lesions seen in those species were reported to be similar to those in humans and macaques, but were not described.22,36
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