{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T21:32:52Z","timestamp":1761168772792,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-24-1039619-01-RMC"],"award-info":[{"award-number":["RSG-24-1039619-01-RMC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"IDeA CTR","doi-asserted-by":"publisher","award":["5U54GM104942-03"],"award-info":[{"award-number":["5U54GM104942-03"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Since its emergence, COVID-19\u2014caused by the novel coronavirus SARS-CoV-2\u2014has affected millions globally and led to over 1.2 million deaths in the United States alone. This global impact, coupled with the emergence of five new human coronaviruses over the past two decades, underscores the urgency of understanding its pathogenic mechanisms at the molecular level\u2014not only for managing the current pandemic but also preparing for future outbreaks. Small non-coding RNAs (sncRNAs) critically regulate host and viral gene expression, including antiviral responses. Among the molecular regulators implicated in antiviral defense, the microRNA-processing enzyme Drosha has emerged as a particularly intriguing factor. In addition to its canonical role, Drosha also exerts a non-canonical, interferon-independent antiviral function against several RNA viruses. Methods: To investigate this, we employed q\/RT-PCR, Western blot, and immunocytochemistry\/immunofluorescence in an immortalized normal human lung\/bronchial epithelial cell line (NuLi-1), as well as a human colorectal carcinoma Drosha CRISPR knockout cell line. Results: In this study, we observed a striking shift in Drosha isoform expression following infection with multiple SARS-CoV-2 variants. This shift was absent following treatment with the viral mimetic poly (I:C) or infection with other RNA viruses, including the non-severe coronaviruses HCoV-OC43 and HCoV-229E. We also identified a distinct alteration in Drosha\u2019s cellular localization post SARS-CoV-2 infection. Moreover, Drosha ablation led to reduced expression of SARS-CoV-2 genomic and sub-genomic targets. Conclusions: Together, these observations not only elucidate a novel aspect of Drosha\u2019s antiviral role but also advance our understanding of SARS-CoV-2 host\u2013pathogen interactions, highlighting potential therapeutic avenues for future human coronavirus infections.<\/jats:p>","DOI":"10.3390\/genes16101239","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:44:10Z","timestamp":1760957050000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 Infection of Lung Epithelia Leads to an Increase in the Cleavage and Translocation of RNase-III Drosha; Loss of Drosha Is Associated with a Decrease in Viral Replication"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-928X","authenticated-orcid":false,"given":"Michael T.","family":"Winters","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6142-8033","authenticated-orcid":false,"given":"Emily S.","family":"Westemeier-Rice","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis W.","family":"Rawson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7984-3126","authenticated-orcid":false,"given":"Kiran J.","family":"Patel","sequence":"additional","affiliation":[{"name":"West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel M.","family":"Sankey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Dixon-Gross","sequence":"additional","affiliation":[{"name":"Department of Biology, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9684-4598","authenticated-orcid":false,"given":"Olivia R.","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasrin","family":"Hashemipour","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4728-0846","authenticated-orcid":false,"given":"McKenna L.","family":"Carroll","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella R.","family":"Wilkerson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","unstructured":"National Center for Health Statistics (2025, August 24). 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