{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:47:54Z","timestamp":1780490874412,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["Ho32298\/2-1"],"award-info":[{"award-number":["Ho32298\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["1088242"],"award-info":[{"award-number":["1088242"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council Project","doi-asserted-by":"publisher","award":["Ho32298\/2-1"],"award-info":[{"award-number":["Ho32298\/2-1"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council Project","doi-asserted-by":"publisher","award":["1088242"],"award-info":[{"award-number":["1088242"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Government Research Training Stipend Scholarship","award":["Ho32298\/2-1"],"award-info":[{"award-number":["Ho32298\/2-1"]}]},{"name":"Australian Government Research Training Stipend Scholarship","award":["1088242"],"award-info":[{"award-number":["1088242"]}]},{"name":"The University of Sydney Postgraduate Merit Award","award":["Ho32298\/2-1"],"award-info":[{"award-number":["Ho32298\/2-1"]}]},{"name":"The University of Sydney Postgraduate Merit Award","award":["1088242"],"award-info":[{"award-number":["1088242"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>CD8+ T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by reduced effector function, failure to clear virus, and the upregulation of inhibitory receptors, including programmed cell death 1 (PD-1). However, exhausted T cell responses can be \u201cre-invigorated\u201d by inhibiting PD-1 or the primary ligand of PD-1: PD-L1. Further, the absence of the type I interferon receptor IFNAR1 also results in T cell exhaustion and virus persistence in lymphocytic choriomeningitis virus Armstrong (LCMV-Arm)-infected mice. In this study, utilizing single- and double-knockout mice, we aimed to determine whether ablation of PD-1 could restore T cell functionality in the absence of IFNAR1 signalling in LCMV-Arm-infected mice. Surprisingly, this did not re-invigorate the T cell response and instead, it converted chronic LCMV-Arm infection into a lethal disease characterized by severe lung inflammation with an infiltration of neutrophils and T cells. Depletion of CD8+ T cells, but not neutrophils, rescued mice from lethal disease, demonstrating that IFNAR1 is required to prevent T cell exhaustion and virus persistence in LCMV-Arm infection, and in the absence of IFNAR1, PD-L1 is required for survival. This reveals an important interplay between IFNAR1 and PD-L1 with implications for therapeutics targeting these pathways.<\/jats:p>","DOI":"10.3390\/v16030390","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T06:07:53Z","timestamp":1709273273000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CD8+ T Cells Mediate Lethal Lung Pathology in the Absence of PD-L1 and Type I Interferon Signalling following LCMV Infection"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6787-6195","authenticated-orcid":false,"given":"Alanna G.","family":"Spiteri","sequence":"first","affiliation":[{"name":"Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-0309","authenticated-orcid":false,"given":"Tamara","family":"Suprunenko","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Cutts","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Suen","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Ashhurst","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney","family":"Viengkhou","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-9772","authenticated-orcid":false,"given":"Nicholas J. C.","family":"King","sequence":"additional","affiliation":[{"name":"Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Cytometry, The University of Sydney and Centenary Institute, Sydney, NSW 2050, Australia"},{"name":"The University of Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"The University of Sydney Nano Institute, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5111-3978","authenticated-orcid":false,"given":"Markus J.","family":"Hofer","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"The University of Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Suprunenko, T., and Hofer, M.J. 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