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

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Nelli, Rahul K.
Phadke, Kruttika-S
Castillo, Gino
Yen, Lu
Saunders, Amy
Rauh, Rolf
Nelson, William
Bellaire, Bryan H.
Major Professor
Committee Member
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Springer Nature
Giménez-Lirola, Luis
Associate Professor
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Veterinary Diagnostic and Production Animal Medicine
The mission of VDPAM is to educate current and future food animal veterinarians, population medicine scientists and stakeholders by increasing our understanding of issues that impact the health, productivity and well-being of food and fiber producing animals; developing innovative solutions for animal health and food safety; and providing the highest quality, most comprehensive clinical practice and diagnostic services. Our department is made up of highly trained specialists who span a wide range of veterinary disciplines and species interests. We have faculty of all ranks with expertise in diagnostics, medicine, surgery, pathology, microbiology, epidemiology, public health, and production medicine. Most have earned certification from specialty boards. Dozens of additional scientists and laboratory technicians support the research and service components of our department.
Organizational Unit
Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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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.
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.