{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:48:14Z","timestamp":1788432494347,"version":"build-2803163510"},"reference-count":48,"publisher":"The Company of Biologists","issue":"13","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21AI157909"],"award-info":[{"award-number":["R21AI157909"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R15AG069544"],"award-info":[{"award-number":["R15AG069544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R15AG076370"],"award-info":[{"award-number":["R15AG076370"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1I01BX002670"],"award-info":[{"award-number":["1I01BX002670"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["5I01BX005428"],"award-info":[{"award-number":["5I01BX005428"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1I01BX004281"],"award-info":[{"award-number":["1I01BX004281"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"crossref","award":["7-20-COVID-149"],"award-info":[{"award-number":["7-20-COVID-149"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["PR170067"],"award-info":[{"award-number":["PR170067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>We investigated the role of telomerase and telomere repeat-binding factor 2 (TRF2 or TERF2) in T-cell dysfunction in chronic viral infection. We found that the expression and activity of telomerase in CD4+ T (CD4T) cells from patients with hepatitis C virus (HCV) infections or people living with HIV (PLWH) were intact, but TRF2 expression was significantly inhibited at the post-transcriptional level, suggesting that TRF2 inhibition is responsible for the CD4T cell dysfunction observed during chronic viral infection. Silencing TRF2 expression in CD4T cells derived from healthy subjects induced telomeric DNA damage and CD4T cell dysfunction without affecting telomerase activity or translocation \u2013 similar to what we observed in CD4T cells from HCV patients and PLWH. These findings indicate that premature T-cell aging and dysfunction during chronic HCV or HIV infection are primarily caused by chronic immune stimulation and T-cell overactivation and\/or proliferation that induce telomeric DNA damage due to TRF2 inhibition, rather than telomerase disruption. This study suggests that restoring TRF2 presents a novel approach to prevent telomeric DNA damage and premature T-cell aging, thus rejuvenating T-cell functions during chronic viral infection.<\/jats:p>","DOI":"10.1242\/jcs.259481","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T09:07:13Z","timestamp":1654506433000},"source":"Crossref","is-referenced-by-count":11,"title":["TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection"],"prefix":"10.1242","volume":"135","author":[{"given":"Lam Ngoc Thao","family":"Nguyen","sequence":"first","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University 1 , Johnson City, TN 37614 , USA"},{"name":"Quillen College of Medicine, East Tennessee State University 2 Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases , , 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