{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:25:19Z","timestamp":1792571119279,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            During some persistent viral infections, virus-specific T-cell responses wane due to the antigen-specific deletion or functional inactivation (i.e., exhaustion) of responding CD8 T cells. T-cell exhaustion often correlates with high viral load and is associated with the expression of the inhibitory receptor PD-1. In other infections, functional T cells are observed despite high levels of pathogen persistence. The reasons for these different T-cell fates during chronic viral infections are not clear. Here, we tracked the fate of virus-specific CD8 T cells in lymphocytic choriomeningitis virus (LCMV)-infected mice during viral clearance, the persistence of wild-type virus, or the selection and persistence of a viral variant that abrogates the presentation of a single epitope. Viral clearance results in PD-1\n            <jats:sup>lo<\/jats:sup>\n            functional virus-specific CD8 T cells, while the persistence of wild-type LCMV results in high PD-1 levels and T-cell exhaustion. However, following the emergence of a GP35V\u2192A variant virus that abrogates the presentation of the GP33 epitope, GP33-specific CD8 T cells remained functional, continued to show low levels of PD-1, and reexpressed CD127, a marker of memory T-cell differentiation. In the same animals and under identical environmental conditions, CD8 T cells recognizing nonmutated viral epitopes became physically deleted or were PD-1\n            <jats:sup>hi<\/jats:sup>\n            and nonfunctional. Thus, the upregulation of PD-1 and the functional inactivation of virus-specific T cells during chronic viral infection is dependent upon continued epitope recognition. These data suggest that optimal strategies for vaccination should induce high-magnitude broadly specific T-cell responses that prevent cytotoxic T-lymphocyte escape and highlight the need to evaluate the function of vaccine-induced T cells in the context of antigens presented during virus persistence.\n          <\/jats:p>","DOI":"10.1128\/jvi.02524-08","type":"journal-article","created":{"date-parts":[[2009,2,12]],"date-time":"2009-02-12T05:00:28Z","timestamp":1234414828000},"page":"4386-4394","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":124,"title":["Impact of Epitope Escape on PD-1 Expression and CD8 T-Cell Exhaustion during Chronic Infection"],"prefix":"10.1128","volume":"83","author":[{"given":"Joseph N.","family":"Blattman","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Room G211, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Room G211, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Jun","family":"Ha","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Room G211, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert G.","family":"van der Most","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Room G211, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Room G211, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"181","year":"1996","unstructured":"Ahmed, R., L. 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