{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:43:38Z","timestamp":1793151818187,"version":"4.5.0"},"reference-count":68,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH NIAID","doi-asserted-by":"publisher","award":["R01 AI125741"],"award-info":[{"award-number":["R01 AI125741"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH NIAID","doi-asserted-by":"publisher","award":["K99\/R00 AI153537"],"award-info":[{"award-number":["K99\/R00 AI153537"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH NIAID","doi-asserted-by":"publisher","award":["R01 AI148403"],"award-info":[{"award-number":["R01 AI148403"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH NIAID","doi-asserted-by":"publisher","award":["DK127526"],"award-info":[{"award-number":["DK127526"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["T32-GM080202"],"award-info":[{"award-number":["T32-GM080202"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,10,17]]},"abstract":"<jats:p>\n                    Although recent evidence indicates that CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterparts remains unclear. Additionally, whether cell-intrinsic factors such as TCR usage influence CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell fate commitment during persistent infection has not previously been studied. Herein, we perform single-cell RNA sequencing (scRNA-seq) combined with single-cell T cell receptor sequencing (scTCR-seq) on virus-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells isolated from mice infected with chronic lymphocytic choriomeningitis virus (LCMV) infection. We identify several transcriptionally distinct states among the Th1, Tfh, and memory-like T cell subsets that form at the peak of infection, including the presence of a previously unrecognized Slamf7\n                    <jats:sup>+<\/jats:sup>\n                    subset with cytolytic features. We further show that the relative distribution of these populations differs substantially between acute and persistent LCMV infection. Moreover, while the progeny of most T cell clones displays membership within each of these transcriptionally unique populations, overall supporting a one cell-multiple fate model, a small fraction of clones display a biased cell fate decision, suggesting that TCR usage may impact CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell development during chronic infection. Importantly, comparative analyses further reveal both subset-specific and core gene expression programs that are differentially regulated between CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells responding to acute and chronic LCMV infection. Together, these data may serve as a useful framework and allow for a detailed interrogation into the clonal distribution and transcriptional circuits underlying CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation during chronic viral infection.\n                  <\/jats:p>","DOI":"10.7554\/elife.80079","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T06:15:12Z","timestamp":1666073712000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80079","source":"Crossref","is-referenced-by-count":29,"title":["Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7431-8535","authenticated-orcid":true,"given":"Ryan","family":"Zander","sequence":"first","affiliation":[{"name":"Blood Research Institute, Versiti Wisconsin","place":["Milwaukee, United 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