{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:02:58Z","timestamp":1791306178917,"version":"4.3.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia\/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1\n            <jats:italic>tax<\/jats:italic>\n            gene. HTLV-1-infected HeLa cells, like their\n            <jats:italic>tax<\/jats:italic>\n            -transduced counterparts, expressed high levels of p21\n            <jats:sup>\n              <jats:italic>CIP1<\/jats:italic>\n              \/\n              <jats:italic>WAF1<\/jats:italic>\n            <\/jats:sup>\n            and p27\n            <jats:sup>\n              <jats:italic>KIP1<\/jats:italic>\n            <\/jats:sup>\n            , developed mitotic abnormalities, and became arrested in G\n            <jats:sub>1<\/jats:sub>\n            in senescence. In contrast, cells of a human osteosarcoma lineage (HOS) continued to divide after HTLV-1 infection or Tax expression, albeit at a reduced growth rate and with mitotic aberrations. Unique to HOS cells is the dramatic reduction of p21\n            <jats:sup>\n              <jats:italic>CIP1<\/jats:italic>\n              \/\n              <jats:italic>WAF1<\/jats:italic>\n            <\/jats:sup>\n            and p27\n            <jats:sup>\n              <jats:italic>KIP1<\/jats:italic>\n            <\/jats:sup>\n            expression, which is in part associated with the constitutive activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway. The loss of p21\n            <jats:sup>\n              <jats:italic>CIP1<\/jats:italic>\n              \/\n              <jats:italic>WAF1<\/jats:italic>\n            <\/jats:sup>\n            and p27\n            <jats:sup>\n              <jats:italic>KIP1<\/jats:italic>\n            <\/jats:sup>\n            in HOS cells apparently allows HTLV-1- and Tax-induced G\n            <jats:sub>1<\/jats:sub>\n            arrest to be bypassed. Finally, HTLV-1 infection and Tax expression also cause human SupT1 T cells to arrest in the G\n            <jats:sub>1<\/jats:sub>\n            phase of the cell cycle. These results suggest that productive HTLV-1 infection ordinarily leads to Tax-mediated G\n            <jats:sub>1<\/jats:sub>\n            arrest. However, T cells containing somatic mutations that inactivate p21\n            <jats:sup>\n              <jats:italic>CIP1<\/jats:italic>\n              \/\n              <jats:italic>WAF1<\/jats:italic>\n            <\/jats:sup>\n            and p27\n            <jats:sup>\n              <jats:italic>KIP1<\/jats:italic>\n            <\/jats:sup>\n            may continue to proliferate after HTLV-1 infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer.\n          <\/jats:p>","DOI":"10.1128\/jvi.00091-08","type":"journal-article","created":{"date-parts":[[2008,7,3]],"date-time":"2008-07-03T00:44:25Z","timestamp":1215045865000},"page":"8442-8455","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Human T-Cell Leukemia Virus Type 1 Infection Leads to Arrest in the G\n            <sub>1<\/sub>\n            Phase of the Cell Cycle"],"prefix":"10.1128","volume":"82","author":[{"given":"Meihong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangpeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoying","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Merling","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chou-Zen","family":"Giam","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"988","volume":"106","year":"2005","unstructured":"Barnard, A. L., T. Igakura, Y. Tanaka, G. P. Taylor, and C. R. Bangham. 2005. Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes. Blood106:988-995.","journal-title":"Blood"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.03.006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202567"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.6.1571"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1432"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6316502"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2741\/1411"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.18.8461-8468.2001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.19.6207"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507184102"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/08892220050193146"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301649200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080115"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204304"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.1271-1277.1999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601054"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205898"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm761"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.8.4022-4033.2002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406424101"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.15.5269-5281.2003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204364"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.15.6866-6874.2000"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000538200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1145"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00881-X"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208976"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0320360"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-007732"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.9.2069"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2888190"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.15.11154"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1989.tb02289.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209059"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506659103"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.10.3377-3386.2000"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/08892220050193128"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.1.9"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507631103"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.1.633-640.1998"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1501"},{"key":"e_1_3_2_43_2","first-page":"696","volume":"74","year":"1996","unstructured":"Simpson, R. M., T. M. Zhao, B. S. Hubbard, S. Sawasdikosol, and T. J. Kindt. 1996. Experimental acute adult T cell leukemia-lymphoma is associated with thymic atrophy in human T cell leukemia virus type I infection. Lab. Investig.74:696-710.","journal-title":"Lab. Investig."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.7981-7987.1999"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3138"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00130-06"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00091-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00091-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T11:56:06Z","timestamp":1646481366000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00091-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":45,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1128\/JVI.00091-08"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00091-08","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]},"assertion":[{"value":"2008-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}