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

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.

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

“…When compared to B.1 shedders, inflammatory damage was less pronounced in animals exposed to BA.5 shedders. Consistent with previous observations [18][19][20][21] , SARS-CoV-2 1818 antigen was markedly decreased or absent in shedder hamsters by 7 dpi. A low abundance of SARS-CoV-2 antigen was accompanied by mild signs of inflammation (Figure S3d).…”

SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo

“…Infected tissues were fixed in 10% formalin and processed for immuno-staining at 72 hours post infection. Bronchus tissues were also fixed in formalin and then processed for transmission electron microscopy as previously described 41 .…”

Histopathologic Characterization of Experimental Peracute SARS-CoV-2 Infection in the Syrian Hamster

“…The Syrian hamster ACE2 receptor naturally supports SARS-CoV-2 interaction and facilitates viral cellular entry [ 13 ]. To date, experimental infection models in hamsters have limited the evaluation of the peracute phase of disease to 24 h post-inoculation [ 14 ] with most initial work performed at 48 h post inoculation (HPI) [ 13 , 15 ], failing to evaluate the earliest viral tropism and potential lesion formation. Yet, in all cases, a full natural history study evaluating peracute through acute phase of infection in a singular experimental inoculation is lacking.…”