{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:28:49Z","timestamp":1791386929313,"version":"4.3.3"},"reference-count":29,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation for Young Scientists of China","award":["32402729"],"award-info":[{"award-number":["32402729"]}]},{"name":"National Science Foundation for Young Scientists of China","award":["2023YFF1000900"],"award-info":[{"award-number":["2023YFF1000900"]}]},{"name":"National Key Research and Development Program of China","award":["32402729"],"award-info":[{"award-number":["32402729"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFF1000900"],"award-info":[{"award-number":["2023YFF1000900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, has inflicted substantial economic losses on the global swine industry. While the severity of infectious disease depends on the dynamic interplay between inoculum dose and host response, the molecular mechanism by which PDCoV dose modulates host immunity remains unclear. Hence, we systematically compared the transcriptomic changes in intestinal epithelial cells infected with different doses of PDCoV, and investigated the relationships between inoculum dose, host immune responses, and disease progression. PDCoV replication peaked at 24 h post-infection, and host responses showed a distinct dose-dependent pattern, with high-dose infection inducing more extensive transcriptional remodeling than low-dose infection. Both doses significantly activated the transcription of STAT1 and its downstream interferon-stimulated genes, while high-dose infection additionally triggered a cytokine storm characterized by excessive IL-6 and TNF-\u03b1 expression. Functional validation demonstrated that STAT1 overexpression markedly inhibited PDCoV infection by enhancing ISRE promoter activity, and overexpression of its downstream ISG15 and MX2 also exerted independent and significant antiviral effects. These findings reveal the biphasic nature of PDCoV dose-dependent regulation of immunopathological mechanisms and identify STAT1 and specific ISGs (ISG15, MX2) as potent antiviral effectors, providing crucial insights into PDCoV pathogenicity and offering promising targets for developing immunomodulatory therapeutics or vaccines to control PDCoV outbreaks in swine.<\/jats:p>","DOI":"10.3390\/ani15172536","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:03:14Z","timestamp":1756393394000},"page":"2536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dose-Dependent Porcine Deltacoronavirus Infection Reveals Linkage Between Infectious Dose and Immune Response"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaocheng","family":"Bao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangxin","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-2253","authenticated-orcid":false,"given":"Wenbin","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-3027","authenticated-orcid":false,"given":"Ming\u2019an","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-3492","authenticated-orcid":false,"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1128\/JVI.06540-11","article-title":"Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus","volume":"86","author":"Woo","year":"2012","journal-title":"J. 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