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A combination therapy of interferon-\u03b1 (IFN-\u03b1) and zidovudin (AZT) shows therapeutic effects in ATL patients, although its mechanism is also obscure. We previously found that viral gene expression in IL-2-dependent HTLV-1-infected T-cells (ILTs) derived from ATL patients was markedly suppressed by stromal cells through a type I IFN response. Here, we investigated the effects of IFN-\u03b1 with or without AZT on viral gene expression and cell growth in ILTs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>ILTs expressed variable but lower amounts of HTLV-1 Tax protein than HTLV-1-transformed HUT102 cells. Following the addition of IFN-\u03b1, the amounts of HTLV-1 p19 in the supernatants of these cells decreased in three days, while HTLV-1 gene expression decreased only in ILTs but not HUT102 cells. IFN-\u03b1 also suppressed the spontaneous HTLV-1 induction in primary ATL cells cultured for 24 h. A time course study using ILTs revealed that the levels of intracellular Tax proteins decreased in the first 24 h after addition of IFN-\u03b1, before the reduction in HTLV-1 mRNA levels. The initial decreases of Tax protein following IFN-\u03b1 treatment were observed in 6 of 7 ILT lines tested, although the reduction rates varied among ILT lines. An RNA-dependent protein kinase (PKR)-inhibitor reversed IFN-mediated suppression of Tax in ILTs. IFN-\u03b1 also induced cell cycle arrest at the G0\/G1 phase and suppressed NF-\u03baB activities in these cells. AZT alone did not affect HTLV-1 gene expression, cell viability or NF-\u03baB activities. AZT combined with IFN-\u03b1 markedly induced cell apoptosis associated with phosphorylation of p53 and induction of p53-responsive genes in ILTs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>IFN-\u03b1 suppressed HTLV-1 gene expression at least through a PKR-mediated mechanism, and also induced cell cycle arrest in ILTs. In combination with AZT, IFN-\u03b1 further induced p53 signaling and cell apoptosis in these cells. These findings suggest that HTLV-1-infected cells at an IL-2-dependent stage retain susceptibility to type I IFN-mediated regulation of viral expression, and partly explain how AZT\/IFN-\u03b1 produces therapeutic effects in ATL.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-4690-10-52","type":"journal-article","created":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T22:19:29Z","timestamp":1369088369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Interferon-\u03b1 (IFN-\u03b1) suppresses HTLV-1 gene expression and cell cycling, while IFN-\u03b1 combined with zidovudin induces p53 signaling and apoptosis in HTLV-1-infected cells"],"prefix":"10.1186","volume":"10","author":[{"given":"Shuichi","family":"Kinpara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Kijiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiko","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amane","family":"Sasada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atae","family":"Utsunomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Kannagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,5,20]]},"reference":[{"key":"3447_CR1","doi-asserted-by":"publisher","first-page":"6476","DOI":"10.1073\/pnas.78.10.6476","volume":"78","author":"Y Hinuma","year":"1981","unstructured":"Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I: Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. 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