{"doi":"10.1101/2023.04.24.538130","title":"How Do Deer Respiratory Epithelial Cells Weather The Initial Storm of SARS-CoV-2?","abstract":"ABSTRACT The potential infectivity of 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 SARS-CoV-2 was assessed throughout 48 hours post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to SARS-COV-2, 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 IL-17 and 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. HIGHLIGHTS White-tailed deer primary respiratory epithelial cells are susceptible to SARS- CoV-2 without causing hyper cytokine gene expression. Downregulation of IL-17 and NF-κB signaling pathways after SARS-CoV-2 infection could be key to the regulated cytokine response in deer cells. Deer innate immune system could play a critical role in early antiviral and tissue repair response following SARS-CoV-2 infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396269,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":841629,"name":"Rahul K. Nelli","orcid":"0000-0001-8765-0943","position":1,"is_corresponding":false},{"id":759975,"name":"Kruttika S. Phadke","orcid":"0000-0002-0661-9520","position":2,"is_corresponding":false},{"id":841627,"name":"Rachel M. Ruden","orcid":"0000-0003-3764-9447","position":3,"is_corresponding":false},{"id":764752,"name":"Yongming Sang","orcid":"0000-0002-2980-2854","position":4,"is_corresponding":false},{"id":724188,"name":"Bryan H. Bellaire","orcid":"0000-0002-4034-6482","position":5,"is_corresponding":false},{"id":1171591,"name":"Luis G. Giménez‐Lirola","orcid":"0000-0002-4407-7996","position":6,"is_corresponding":false},{"id":386018,"name":"Laura C. Miller","orcid":"0000-0002-8946-9416","position":7,"is_corresponding":false},{"id":1171590,"name":"Kaitlyn M. Sarlo Davila","orcid":"0000-0002-0000-4410","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:19:27.044553Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}