How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

Sarlo Davila, Kaitlyn M.; Nelli, Rahul K.; Phadke, Kruttika S.; Ruden, Rachel M.; Sang, Yongming; Bellaire, Bryan H.; Gimenez-Lirola, Luis G.; Miller, Laura C.

doi:10.1128/spectrum.02524-23

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

Journal Article · Tue Feb 06 00:00:00 EST 2024 · Microbiology Spectrum

DOI:https://doi.org/10.1128/spectrum.02524-23· OSTI ID:2471298

^[1]; ^[2]; Phadke, Kruttika S. ^[2]; Ruden, Rachel M. ^[2]; ^[3]; ^[2]; ^[2]; ^[4]

US Dept. of Agriculture (USDA), Ames, IA (United States). Agricultural Research Service (ARS), National Animal Disease Center
Iowa State Univ., Ames, IA (United States)
Tennessee State Univ., Nashville, TN (United States)
US Dept. of Agriculture (USDA), Ames, IA (United States). Agricultural Research Service (ARS), National Animal Disease Center; Kansas State Univ., Manhattan, KS (United States)

The potential infectivity of severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with the SARS-CoV-2 WA1/2020 strain was assessed throughout 48 h post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to virus infection, with significantly (P< 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via interleukin-17 (IL-17) and nuclear factor-κB (NF-κB) signaling pathways. Inhibition of the NF-κB signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans. IMPORTANCE. This study demonstrated that human and white-tailed deer primary respiratory epithelial cells are susceptible to the SARS-CoV-2 WA1/2020 strain infection. However, the comparative transcriptomic analysis revealed that deer cells could limit viral replication without causing hypercytokinemia by downregulating IL-17 and NF-κB signaling pathways. Identifying differentially expressed genes in human and deer cells that modulate key innate immunity pathways during the early infection will lead to developing targeted therapies toward preventing or mitigating the “cytokine storm” often associated with severe cases of coronavirus disease 19 (COVID-19). Moreover, results from this study will aid in identifying novel prognostic biomarkers in predicting SARS-CoV-2 adaption and transmission in deer and associated cervids.

View Accepted Manuscript (DOE)

Research Organization:: Iowa State Univ., Ames, IA (United States; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: US Department of Agriculture (USDA); USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471298

Journal Information:: Microbiology Spectrum, Journal Name: Microbiology Spectrum Journal Issue: 2 Vol. 12; ISSN 2165-0497

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
IL-17
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cytokine storm
deer
epithelial cells
human

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

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