{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T22:18:03Z","timestamp":1787091483114,"version":"build-2736575974"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01 AI15180"],"award-info":[{"award-number":["U01 AI15180"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (\u03b2-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to \u03b2-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3\/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after \u03b2-CoVs or mock infection of Calu-3\/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (<jats:italic>BST2<\/jats:italic>), Z-DNA Binding Protein 1 (<jats:italic>ZBP1<\/jats:italic>), C-X-C Motif Chemokine Ligand 11 (<jats:italic>CXCL11<\/jats:italic>), and Interferon Induced Transmembrane Protein 1 (<jats:italic>IFITM1<\/jats:italic>), were identified as potential drug targets against \u03b2-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.<\/jats:p>","DOI":"10.1371\/journal.pone.0317921","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T18:45:36Z","timestamp":1738089936000},"page":"e0317921","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0274-3900","authenticated-orcid":true,"given":"Vivian Y.","family":"Tat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra K.","family":"Drelich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-0695","authenticated-orcid":true,"given":"Pinghan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3881-737X","authenticated-orcid":true,"given":"Kamil","family":"Khanipov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C.","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Widen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Te Kent","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-2767","authenticated-orcid":true,"given":"George","family":"Golovko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"pone.0317921.ref001","unstructured":"SARS Basics Fact Sheet | CDC Archive [Internet]. 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