{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:32:20Z","timestamp":1776918740235,"version":"3.51.2"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2004,5,1]],"date-time":"2004-05-01T00:00:00Z","timestamp":1083369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Viral FLIPs (vFLIPs) interfere with apoptosis signaling by death-domain-containing receptors in the TNFR superfamily (death receptors). In this study, we show that T cell-specific transgenic expression of MC159-vFLIP from the human Molluscum contagiosum virus blocks CD95-induced apoptosis in thymocytes and peripheral T cells, but also impairs postactivation survival of in vitro activated primary T cells despite normal early activation parameters. MC159 vFLIP impairs T cell development to a lesser extent than does Fas-associated death domain protein deficiency or another viral FLIP, E8. In the periphery, vFLIP expression leads to a specific deficit of functional memory CD8+ T cells. After immunization with a protein Ag, Ag-specific CD8+ T cells initially proliferate, but quickly disappear and fail to produce Ag-specific memory CD8+ T cells. Viral FLIP transgenic mice exhibit impaired CD8+ T cell responses to lymphocytic choriomeningitis virus and Trypanosoma cruzi infections, and a specific defect in CD8+ T cell recall responses to influenza virus was seen. These results suggest that vFLIP expression in T cells blocks signals necessary for the sustained survival of CD8+ T cells and the generation of CD8+ T cell memory. Through this mechanism, vFLIP proteins expressed by T cell tropic viruses may impair the CD8+ T cell immune responses directed against them.<\/jats:p>","DOI":"10.4049\/jimmunol.172.10.6313","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:55:35Z","timestamp":1398027335000},"page":"6313-6323","source":"Crossref","is-referenced-by-count":33,"title":["Viral FLIP Impairs Survival of Activated T Cells and Generation of CD8+ T Cell Memory"],"prefix":"10.1093","volume":"172","author":[{"given":"Zhengqi","family":"Wu","sequence":"first","affiliation":[{"name":"Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Roberts","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Porter","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabianne","family":"Walker","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Department of Microbiology, and University School of Medicine, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kelly","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Gadina","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth M","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto de Biofi\u0301sica Carlos Chagas Filho, Centro de Cie\u0302ncias da Sau\u0301de, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A","family":"DosReis","sequence":"additional","affiliation":[{"name":"Instituto de Biofi\u0301sica Carlos Chagas Filho, Centro de Cie\u0302ncias da Sau\u0301de, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela F","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Biofi\u0301sica Carlos Chagas Filho, Centro de Cie\u0302ncias da Sau\u0301de, Universidade Federal do Rio de Janeiro , Rio de Janeiro ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren J","family":"Leonard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Department of Microbiology, and University School of Medicine, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M","family":"Siegel","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,5,15]]},"reference":[{"key":"2026020211295911300_R1","first-page":"469","volume-title":"Nat. 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