biostudies-literatureAlfi OSamueli Institute (Samueli Institute for Information Biology)Rothschild Foundation Hanadiv Europe (Rothschild Foundation (Europe))Rothschild Foundation Hanadiv Europe (Rothschild FoundationSamueli InstituteIsrael Science FoundationIsrael Science Foundation (ISF)Israeli Ministry of Science &amp; Technology7th Framework Program ERA-NETIsraeli Science Ministrye0013021https://www.ebi.ac.uk/biostudies/studies/S-EPMC8223920biostudies-literatureUnknown95(14)The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues <i>ex vivo</i>, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respJournal of virologyHuman Nasal and Lung Tissues Infected <i>Ex Vivo</i> with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract.PMC8223920530/183-16964Izhar UJonas WMadgar OElgavish SIves JOberbaum MNevo YWalter JPikarsky EYakirevitch AWald OBronstein MAlfi OZakay-Rones ZWolf DGDagan EFeinmesser GPanet AVorontsov OWandel OOiknine-Djian EfalseHuman Nasal and Lung Tissues Infected <i>Ex Vivo</i> with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract.The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues <i>ex vivo</i>, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting resp2021-01-01T00:00:00Z2021 Jun2025-04-04T11:12:42.696Z2022-02-11T14:29:06.534ZS-EPMC82239203389317010.1128/jvi.00130-2110.1128/JVI.00130-21