{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T14:04:12Z","timestamp":1767276252451,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>E2 is the major structural glycoprotein of the classical swine fever virus (CSFV). E2 has been shown to be involved in important virus functions such as replication and virulence in swine. Using the yeast two-hybrid system, we previously identified several host proteins specifically interacting with CSFV E2. Here, we analyze the protein interaction of E2 with SERTA domain containing protein 1 (SERTAD1), a factor involved in the stimulation of the transcriptional activities of different host genes. We have confirmed that the interaction between these two proteins occurs in CSFV-infected swine cells by using a proximity ligation assay and confocal microscopy. Amino acid residues in the CSFV E2 protein that are responsible for mediating the interaction with SERTAD1 were mapped by a yeast two-hybrid approach using a randomly mutated E2 library. Using that information, a recombinant CSFV mutant (E2\u0394SERTAD1v) that harbors substitutions in those residues mediating the protein-interaction with SERTAD1 was developed and used to study the role of the E2-SERTAD1 interaction in viral replication and virulence in swine. CSFV E2\u0394SERTAD1v, when compared to the parental BICv, showed a clearly decreased ability to replicate in the SK6 swine cell line and a more severe replication defect in primary swine macrophage cultures. Importantly, 80% of animals infected with E2\u0394SERTAD1v survived infection, remaining clinically normal during the 21-day observational period. This result would indicate that the ability of CSFV E2 to bind host SERTAD1 protein during infection plays a critical role in virus virulence.<\/jats:p>","DOI":"10.3390\/v12040421","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine"],"prefix":"10.3390","volume":"12","author":[{"given":"Elizabeth A.","family":"Vuono","sequence":"first","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Department of Pathobiology and Population Medicine, Mississippi State University, P.O. Box 6100, Starkville, MS 39762, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Ramirez-Medina","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Azzinaro","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-8015","authenticated-orcid":false,"given":"Keith A.","family":"Berggren","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayushi","family":"Rai","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Pruitt","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ediane","family":"Silva","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauro","family":"Velazquez-Salinas","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"},{"name":"Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel V.","family":"Borca","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-0233","authenticated-orcid":false,"given":"Douglas P.","family":"Gladue","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"unstructured":"Rice, C. 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