{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:27:00Z","timestamp":1792092420572,"version":"4.4.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Intramural Research Program of National Cancer Institute"},{"DOI":"10.13039\/501100007461","name":"Pezcoller Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007461","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["13378"],"award-info":[{"award-number":["13378"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universita degli Studi di Padova","doi-asserted-by":"publisher","award":["CPDA124913\/12"],"award-info":[{"award-number":["CPDA124913\/12"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human T-cell leukemia virus type 1 (HTLV-1) expression depends on the concerted action of Tax, which drives transcription of the viral genome, and Rex, which favors expression of incompletely spliced mRNAs and determines a 2-phase temporal pattern of viral expression. In the present study, we investigated the Rex dependence of the complete set of alternatively spliced HTLV-1 mRNAs. Analyses of cells transfected with Rex\u2013wild-type and Rex-knockout HTLV-1 molecular clones using splice site-specific quantitative reverse transcription (qRT)-PCR revealed that mRNAs encoding the p30Tof, p13, and p12\/8 proteins were Rex dependent, while the\n            <jats:italic>p21rex<\/jats:italic>\n            mRNA was Rex independent. These findings provide a rational explanation for the intermediate-late temporal pattern of expression of the\n            <jats:italic>p30tof<\/jats:italic>\n            ,\n            <jats:italic>p13<\/jats:italic>\n            , and\n            <jats:italic>p12\/8<\/jats:italic>\n            mRNAs described in previous studies. All the Rex-dependent mRNAs contained a 75-nucleotide intronic region that increased the nuclear retention and degradation of a reporter mRNA in the absence of other viral sequences. Selective 2\u2032-hydroxyl acylation analyzed by primer extension (SHAPE) analysis revealed that this sequence formed a stable hairpin structure. Cell cycle synchronization experiments indicated that mitosis partially bypasses the requirement for Rex to export Rex-dependent HTLV-1 transcripts. These findings indicate a link between the cycling properties of the host cell and the temporal pattern of viral expression\/latency that might influence the ability of the virus to spread and evade the immune system.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            HTLV-1 is a complex retrovirus that causes two distinct pathologies termed adult T-cell leukemia\/lymphoma and tropical spastic paraparesis\/HTLV-1-associated myelopathy in about 5% of infected individuals. Expression of the virus depends on the concerted action of Tax, which drives transcription of the viral genome, and Rex, which favors expression of incompletely spliced mRNAs and determines a 2-phase temporal pattern of virus expression. The findings reported in this study revealed a novel\n            <jats:italic>cis<\/jats:italic>\n            -acting regulatory element and indicated that mitosis partially bypasses the requirement for Rex to export Rex-dependent HTLV-1 transcripts. Our results add a layer of complexity to the mechanisms controlling the expression of alternatively spliced HTLV-1 mRNAs and suggest a link between the cycling properties of the host cell and the temporal pattern of viral expression\/latency that might influence the ability of the virus to spread and evade the immune system.\n          <\/jats:p>","DOI":"10.1128\/jvi.02298-15","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T03:34:17Z","timestamp":1447904057000},"page":"1486-1498","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Expression of Alternatively Spliced Human T-Cell Leukemia Virus Type 1 mRNAs Is Influenced by Mitosis and by a Novel\n            <i>cis<\/i>\n            -Acting Regulatory Sequence"],"prefix":"10.1128","volume":"90","author":[{"given":"Ilaria","family":"Cavallari","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Rende","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion K.","family":"Bona","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sztuba-Solinska","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, National Cancer Institute, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Silic-Benussi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Tognon","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-8796","authenticated-orcid":false,"given":"Stuart F. 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