{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:32:08Z","timestamp":1782145928922,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Juvenile Diabetes Research Foundation &amp; nPOD-V","award":["JDRF grant 25-2012-770"],"award-info":[{"award-number":["JDRF grant 25-2012-770"]}]},{"name":"Italian Ministry of Health","award":["grant PE-2013-02357094"],"award-info":[{"award-number":["grant PE-2013-02357094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Background: Hashimoto\u2019s thyroiditis and Graves\u2019 disease are autoimmune thyroid disorders (AITD) of unknown origin. Enterovirus (EV) infection of thyroid cells has been implicated as a possible initiator of cell damage and of organ-specific autoimmunity. We asked whether persistent infection of human epithelial cells with EV strains obtained from thyroid tissue of AITD patients could be associated with transcriptional changes capable of fostering immunopathology. Methods: EV isolates obtained from thyroid tissue of AITD cases were used to infect the AV3 epithelial cell line. AV3 cells incubated with a virus-free medium from thyroid tissue of subjects without evidence of thyroid autoimmunity were used as uninfected controls. Transcripts of immune-related genes were compared in infected vs. uninfected cells. Results: The EV genome and antigens were detected only in the cells exposed to AITD-derived virus isolates, not in control cells. Persistent EV infection, while suppressing transcription of several type I IFN and cytokine determinants, was associated with enhanced transcription of NFKB1\/RELA, IFNAR1, JAK1\/STAT1, i.e., the determinants that play key immunologic roles. Infection also led to upregulation of the CCL2 chemokine and the IL-18 pro-inflammatory interleukin. Conclusion: As in the case of EV strains obtained from autoimmune diabetes, results show that the EV strains that are present in the thyroid of AITD cases do repress IFN and cytokine pathways. JAK1\/STAT1 upregulation supports activation of TLR pathways and aberrant T cell signaling. In the early phases of AITD, our results highlight the potential benefit of interventions aimed at blocking the viral infection and easing the inflammatory response.<\/jats:p>","DOI":"10.3390\/microorganisms9040876","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T21:59:49Z","timestamp":1618869589000},"page":"876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune Transcriptome of Cells Infected with Enterovirus Strains Obtained from Cases of Autoimmune Thyroid Disease"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-8249","authenticated-orcid":false,"given":"Anello Marcello","family":"Poma","sequence":"first","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Clinical Area, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Salehi","family":"Hammerstad","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Specialist Center Pilestredet Park, Pilestredet Park 12.A, 0176 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Genoni","sequence":"additional","affiliation":[{"name":"Medical Microbiology, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-7080","authenticated-orcid":false,"given":"Alessio","family":"Basolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9899","authenticated-orcid":false,"given":"Knut","family":"Dahl-Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Faculty of Medicine, The University of Oslo, 0316 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-2126","authenticated-orcid":false,"given":"Antonio","family":"Toniolo","sequence":"additional","affiliation":[{"name":"Global Virus Network, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","unstructured":"Patil, N., Rehman, A., and Jialal, I. 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