Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice. Issue 4 (July 2022)

• Record Type: Journal Article
• 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.
• Is Part Of: Veterinary pathology. Volume 59:Issue 4(2022)
• Page Start: 639
• Page End: 647
• Publication Date: 2022-07
• Subjects: COVID-19 -- SARS-CoV-2 -- severe acute respiratory syndrome -- coronavirus -- pathology -- immunohistochemistry -- ultrastructure; Veterinary pathology -- Periodicals; Pathology, Veterinary -- Periodicals; 636.089607
• DOI: 10.1177/03009858211043084
• Languages: English
• ISSNs: 0300-9858

Abstract

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.