Enhanced apoptosis as a possible mechanism to self-limit SARSCoV- 2 replication in porcine primary respiratory epithelial cells in contrast to human cells

File

2021-GimenezLirolaLuis-EnhancedApoptosis.pdf (2.41 MB)

Date

2021-12-10

Authors

Nelli, Rahul K.
Phadke, Kruttika-S
Castillo, Gino
Yen, Lu
Saunders, Amy
Rauh, Rolf
Nelson, William
Bellaire, Bryan H.
Giménez-Lirola, Luis

Publisher

Springer Nature

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Authors

Giménez-Lirola, Luis

Person

Associate Professor

Organizational Units

Veterinary Diagnostic and Production Animal Medicine

Organizational Unit

Veterinary Microbiology and Preventive Medicine

Organizational Unit

Department

Veterinary Diagnostic and Production Animal MedicineVeterinary Microbiology and Preventive Medicine

Abstract

The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pigs, while later attempts using a higher infectious dose reported viral shedding and seroconversion. This study investigated species-specific cell susceptibility, virus dose-dependent infectivity, and infection kinetics, using primary human (HRECs) and porcine (PRECs) respiratory epithelial cells. Despite higher ACE2 expression in HRECs compared to PRECs, SARS-CoV-2 infected, and replicated in both PRECs and HRECs in a dose-dependent manner. Cytopathic effect was particularly more evident in PRECs than HRECs, showing the hallmark morphological signs of apoptosis. Further analysis confirmed an early and enhanced apoptotic mechanism driven through caspase 3/7 activation, limiting SARS-CoV-2 propagation in PRECs compared to HRECs. Our findings shed light on a possible mechanism of resistance of pigs to SARS-CoV-2 infection, and it may hold therapeutic value for the treatment of COVID-19.

Comments

This article is published as Nelli, Rahul K., Kruttika-S. Phadke, Gino Castillo, Lu Yen, Amy Saunders, Rolf Rauh, William Nelson, Bryan H. Bellaire, and Luis G. Giménez-Lirola. "Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells." Cell Death Discovery 7, no. 1 (2021): 1-10. DOI: 10.1038/s41420-021-00781-w. Copyright 2021 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission.