{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:48:14Z","timestamp":1785433694742,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI150585"],"award-info":[{"award-number":["P01AI150585"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI134907"],"award-info":[{"award-number":["R01AI134907"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P01AI150585"],"award-info":[{"award-number":["P01AI150585"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI134907"],"award-info":[{"award-number":["R01AI134907"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-\u03b2 while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFN\u03b2 and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFN\u03b2 and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85.<\/jats:p>","DOI":"10.3390\/v18070729","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PTPN13 Contributes to Ebola Virus-Induced Immune Dysregulation via Dephosphorylation of IRF3 and PI3K-p85"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-0208","authenticated-orcid":false,"given":"Abbey N.","family":"Warren","sequence":"first","affiliation":[{"name":"Center for Virus-Host-Innate-Immunity, RBHS Institute for Infectious and Inflammatory Diseases, and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gonzalez-Orozco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Kuzmin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3631-3669","authenticated-orcid":false,"given":"Sreeja","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Soto Acosta","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Kalveram","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"van Tol","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7668-892X","authenticated-orcid":false,"given":"Adam","family":"Hage","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmanava","family":"Behera","sequence":"additional","affiliation":[{"name":"Center for Virus-Host-Innate-Immunity, RBHS Institute for Infectious and Inflammatory Diseases, and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9494-3748","authenticated-orcid":false,"given":"Yoatzin","family":"Pe\u00f1aflor-Tellez","sequence":"additional","affiliation":[{"name":"Center for Virus-Host-Innate-Immunity, RBHS Institute for Infectious and Inflammatory Diseases, and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1931-4555","authenticated-orcid":false,"given":"William","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-9122","authenticated-orcid":false,"given":"Matthew T.","family":"Weirauch","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-8960","authenticated-orcid":false,"given":"Alexander","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bukreyev","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-5444","authenticated-orcid":false,"given":"Ricardo","family":"Rajsbaum","sequence":"additional","affiliation":[{"name":"Center for Virus-Host-Innate-Immunity, RBHS Institute for Infectious and Inflammatory Diseases, and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"},{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-020-0147-3","article-title":"Ebola Virus Disease","volume":"6","author":"Jacob","year":"2020","journal-title":"Nat. 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