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Vet Pathol. 2021 Sep 01;3009858211043084. doi: 10.1177/03009858211043084. Epub 2021 Sep 01.

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

Veterinary pathology

Hui-Ling Yen, Sophie Valkenburg, Sin Fun Sia, Ka Tim Choy, J S Malik Peiris, Karen H M Wong, Nicholas Crossland, Florian Douam, John M Nicholls

Affiliations

  1. The University of Hong Kong, Pok Fu Lam, Hong Kong.
  2. Boston University, Boston, MA, USA.

PMID: 34467820 PMCID: PMC8721337 DOI: 10.1177/03009858211043084

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.

Keywords: COVID-19; SARS-CoV-2; coronavirus; immunohistochemistry; pathology; severe acute respiratory syndrome; ultrastructure

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