{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:43:02Z","timestamp":1790797382417,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011459","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NCI","award":["P01CA100730"],"award-info":[{"award-number":["P01CA100730"]}]},{"name":"The Ohio State University Pelotonia Fellowship Program"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia\/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently expressed in asymptomatic carriers and ATL patients, suggesting its importance in the development and maintenance of HTLV-1 leukemic cells. Our previous work found Hbz protein is dispensable for virus-mediated T-cell immortalization but enhances viral persistence. We and others have also shown that\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA promotes T-cell proliferation. In our current studies, we evaluated the role of\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA on HTLV-1-mediated immortalization\n                    <jats:italic>in vitro<\/jats:italic>\n                    as well as\n                    <jats:italic>in vivo<\/jats:italic>\n                    persistence and disease development. We generated mutant proviral clones to examine the individual contributions of\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA,\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA secondary structure (stem-loop), and Hbz protein. Wild-type (WT) and all mutant viruses produced virions and immortalized T-cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Viral persistence and disease development were also evaluated\n                    <jats:italic>in vivo<\/jats:italic>\n                    by infection of a rabbit model and humanized immune system (HIS) mice, respectively. Proviral load and sense and antisense viral gene expression were significantly lower in rabbits infected with mutant viruses lacking Hbz protein compared to WT or virus with an altered\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA stem-loop (M3 mutant). HIS mice infected with Hbz protein-deficient viruses showed significantly increased survival times compared to animals infected with WT or M3 mutant virus. Altered\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA secondary structure, or loss of\n                    <jats:italic>hbz<\/jats:italic>\n                    mRNA or protein, has no significant effect on T-cell immortalization induced by HTLV-1\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; however, the Hbz protein plays a critical role in establishing viral persistence and leukemogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011459","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T13:31:38Z","timestamp":1686922298000},"page":"e1011459","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["HTLV-1 Hbz protein, but not hbz mRNA secondary structure, is critical for viral persistence and disease development"],"prefix":"10.1371","volume":"19","author":[{"given":"Victoria","family":"Maksimova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasha","family":"Wilkie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Phelps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrine","family":"Melvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianbo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Niewiesk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-3705","authenticated-orcid":true,"given":"Amanda R.","family":"Panfil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"issue":"12","key":"ppat.1011459.ref001","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"BJ Poiesz","year":"1980","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"ppat.1011459.ref002","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1073\/pnas.79.6.2031","article-title":"Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease","volume":"79","author":"M Yoshida","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1011459.ref003","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: clinical and hematologic features of 16 cases","volume":"50","author":"T Uchiyama","year":"1977","journal-title":"Blood"},{"issue":"2","key":"ppat.1011459.ref004","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1053\/j.semdp.2019.04.003","article-title":"Molecular biology of human T cell leukemia virus","volume":"37","author":"L. 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