Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice

• Published in: Veterinary pathology Vol. 59; no. 4; pp. 639 - 647
• Main Authors: Yen, Hui-Ling, Valkenburg, Sophie, Sia, Sin Fun, Choy, Ka Tim, Peiris, J. S. Malik, Wong, Karen H. M., Crossland, Nicholas, Douam, Florian, Nicholls, John M.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2022
• Subjects: Original; COVID-19; SARS-CoV-2; pathology; coronavirus; immunohistochemistry; ultrastructure; severe acute respiratory syndrome
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/03009858211043084

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.