{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Demoulins T"],"funding":["NIAID NIH HHS","National Institutes of Health","Seattle Children's Research Institute"],"pagination":["77-86"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12924682"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["567"],"pubmed_abstract":["Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/β expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNαβR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers."],"journal":["Virology"],"pubmed_title":["Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection."],"pmcid":["PMC12924682"],"funding_grant_id":["5P30CA015704","AI103748","R21 AI154363","R01 AI132819","AI154363","AI132819","R03 AI103748"],"pubmed_authors":["Reed SJ","Lamarre A","Kettaf N","Sarkar S","Demoulins T","Kalinke U","Kalia V","Charpentier T","Sekaly RP","Gauchat D","Ahmed R","Baron ML"],"additional_accession":[]},"is_claimable":false,"name":"Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection.","description":"Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/β expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNαβR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-07-09T11:48:38.793Z","creation":"2026-07-09T11:01:59.987Z"},"accession":"S-EPMC12924682","cross_references":{"pubmed":["35032866"],"doi":["10.1016/j.virol.2021.12.007"]}}