{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:48:12Z","timestamp":1762181292579,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-NR076878"],"award-info":[{"award-number":["RS-2023-NR076878"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>There is increasing research interest in the ORF3 accessory protein of PEDV as a critical element for viral virulence. Here, wild type ORF3 (ORF3wt) gene was constructed in pEGFP-C1 vector. Additionally, two truncation mutants, ORF3-N (1-98 amino acids [aa]) and ORF3-C (99-224 aa) were inserted in the same vector. Results of ORF3 expression revealed early cytoplasmic localization but 12 h after transfection, ORF3 accumulated around the nucleus, especially ORF3-N. This caused chromosome condensation and morphological distortion that culminated in cell death. In comparison with the native cells expressing GFP alone, ORF3wt-induced lethality was 6.61% above baseline while ORF3- C expression resulted in moderate increase in cell death (0.64%). ORF3-N was affected the most with 220.32% increased lethality. It was, therefore, inferred that the ORF3 gene encodes a protein that causes nuclear damage, distorts cell morphology and leads to cell death. Furthermore, the role of the protein could be inherent in the N-terminal domain, which consists of the transmembrane domains. These findings underpin the importance of ORF3 gene expression in the host and are rudimental insights for further exploration into the mechanistic interactions of ORF3 and the host, as well as a possible role in pathogenesis in PEDV and other coronaviruses.<\/jats:p>","DOI":"10.3390\/v17111468","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ORF3 Gene of Porcine Epidemic Diarrhea Virus Causes Nuclear and Morphological Distortions with Associated Cell Death"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0428-4473","authenticated-orcid":false,"given":"Ndirangu A.","family":"Kamau","sequence":"first","affiliation":[{"name":"Laboratory of Infectious Diseases, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"},{"name":"Department of Biological Sciences, Technical University of Kenya, Haile Selassie Avenue, Nairobi P.O. Box 52428-00200, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-4939","authenticated-orcid":false,"given":"Jae-Rang","family":"Rho","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, College of Bioscience & Biotechnology, Chungnam National University, 220 Gungdong, Yuseong, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eui-Soon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, College of Bioscience & Biotechnology, Chungnam National University, 220 Gungdong, Yuseong, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Eun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, College of Bioscience & Biotechnology, Chungnam National University, 220 Gungdong, Yuseong, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, College of Bioscience & Biotechnology, Chungnam National University, 220 Gungdong, Yuseong, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-7976","authenticated-orcid":false,"given":"Gianmarco","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, Polo Universitario dell\u2019Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-4924","authenticated-orcid":false,"given":"Hyun-Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF01317606","article-title":"A New Coronavirus-like Particle Associated with Diarrhea in Swine","volume":"58","author":"Pensaert","year":"1978","journal-title":"Arch. 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