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Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, thereby promoting HBV escape from the human innate immune system and establishing persistent infection. However, whether X proteins of Orthohepadnavirus viruses in other species display a similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-\u03b2 (TRIF)-mediated IFN-\u03b2 signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFN\u03b2 signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.<\/jats:p>","DOI":"10.3390\/ijms25073753","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:22:46Z","timestamp":1711628566000},"page":"3753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Conserved Functions of Orthohepadnavirus X Proteins to Inhibit Type-I Interferon Signaling"],"prefix":"10.3390","volume":"25","author":[{"given":"Amonrat","family":"Choonnasard","sequence":"first","affiliation":[{"name":"Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan"},{"name":"Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3577-9718","authenticated-orcid":false,"given":"Maya","family":"Shofa","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan"},{"name":"Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8614-6593","authenticated-orcid":false,"given":"Tamaki","family":"Okabayashi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan"},{"name":"Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan"},{"name":"Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-4399","authenticated-orcid":false,"given":"Akatsuki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan"},{"name":"Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan"},{"name":"Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). 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