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.
Highlights
The ability to infect a wide variety of mammalian and avian species [1], coronavirus infections pose a recurring and continuous threat to human and animal health, the new viral strains emerging from unknown wild animal reservoirs [2,3,4]
Immunohistochemistry (IHC) analysis of the angiotensin-converting enzyme 2 (ACE2) expression on SARS-CoV-2 infection and associated cell death in HRECs and tissue slides corresponded to normal adult human trachea tissue PRECs sections of commercially acquired slides indicated that ACE2 expression was predominantly present on epithelial cells, towards the tracheal epithelial lining (Fig. 1A)
Both PRECs and HRECs cultures were SARS-CoV-2-inoculated with eight different viral doses (MOI 5.0, 5.0 × 10−1, 5.0 × 10−2, 5.0 × 10−3, 5.0 × 10−4, 5.0 × 10−5, 5.0 × 10−6, and 5.0 × 10−7) or mockexpression was not observed in the subepithelial region of the inoculated with inoculation medium, and incubated for 120 h trachea
Summary
The ability to infect a wide variety of mammalian and avian species [1], coronavirus (order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae) infections pose a recurring and continuous threat to human and animal health, the new viral strains emerging from unknown wild animal reservoirs [2,3,4]. Coronavirus infections in humans (e.g., those caused by HCoV-229E and HCoV-OC43 CoV strains) are mild and associated with only common cold symptoms [5,6,7]. Different studies have demonstrated that several animal species, including dogs [14], cats [15], minks [16], ferrets [17], hamsters [18], tigers [19], and deer [20], are susceptible to infection by SARS-CoV-2 through zooanthroponotic (or reverse-zoonotic) transmission [21]
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