{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:43:52Z","timestamp":1790412232467,"version":"4.1.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM144890"],"award-info":[{"award-number":["R01 GM144890"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA258614"],"award-info":[{"award-number":["R01 CA258614"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-19-166-01-TBG"],"award-info":[{"award-number":["RSG-19-166-01-TBG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","award":["821321"],"award-info":[{"award-number":["821321"]}],"id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005188","name":"Tobacco-Related Disease Research Program","doi-asserted-by":"publisher","award":["T33IR6461"],"award-info":[{"award-number":["T33IR6461"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia\/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-\u03baB. Here, we report that genetic deletion of NF-\u03baB1, the prototypic member of the NF-\u03baB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir <jats:italic>in vivo<\/jats:italic>. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-\u03baB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.<\/jats:p>","DOI":"10.1371\/journal.pone.0303138","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:27:38Z","timestamp":1715275658000},"page":"e0303138","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["NF-\u03baB1 deficiency promotes macrophage-derived adrenal tumors but decreases neurofibromas in HTLV-I LTR-Tax transgenic mice"],"prefix":"10.1371","volume":"19","author":[{"given":"Xinxin","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-9814","authenticated-orcid":true,"given":"Zhaoxia","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"issue":"7","key":"pone.0303138.ref001","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3390\/pathogens9070543","article-title":"Mechanisms of oncogenesis by HTLV-1 Tax","volume":"9","author":"S Mohanty","year":"2020","journal-title":"Pathogens"},{"issue":"1","key":"pone.0303138.ref002","doi-asserted-by":"crossref","first-page":"e2018024","DOI":"10.4084\/mjhid.2018.024","article-title":"Human T-cell leukemia virus type I associated with an increased risk of primary malignant neoplasm","volume":"10","author":"A Nakaya","year":"2018","journal-title":"Mediterr J Hematol Infect Dis"},{"issue":"3","key":"pone.0303138.ref003","first-page":"433","article-title":"Tax protein of human T-cell leukemia virus type 1 is required for maintenance of the transformed phenotype","volume":"7","author":"S Yamaoka","year":"1992","journal-title":"Oncogene"},{"issue":"6","key":"pone.0303138.ref004","doi-asserted-by":"crossref","first-page":"714","DOI":"10.3390\/v3060714","article-title":"Human T-cell lymphotropic virus: a model of NF-\u03baB-associated tumorigenesis","volume":"3","author":"Z Qu","year":"2011","journal-title":"Viruses"},{"issue":"1","key":"pone.0303138.ref005","first-page":"413","article-title":"The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells","volume":"10","author":"R Pozzatti","year":"1990","journal-title":"Mol Cell 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