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To develop a better animal model for the investigation of HTLV-1 infection, we established a transgenic (Tg) rat carrying the human CRM1 (hCRM1) gene, which encodes a viral RNA transporter that is a species-specific restriction factor. At first we found that CRM1 expression is elaborately regulated through a pathway involving protein kinase C during lymphocyte activation, initially by posttranscriptional and subsequently by transcriptional mechanisms. This fact led us to use an hCRM1-containing bacterial artificial chromosome clone, which would harbor the entire regulatory and coding regions of the CRM1 gene. The Tg rats expressed hCRM1 protein in a manner similar to expression of intrinsic rat CRM1 in various organs. HTLV-1-infected T-cell lines derived from these Tg rats produced 100- to 10,000-fold more HTLV-1 than did T cells from wild-type rats, and the absolute levels of HTLV-1 were similar to those produced by human T cells. We also observed enhancement of the dissemination of HTLV-1 to the thymus in the Tg rats after intraperitoneal inoculation, although the proviral loads were low in both wild-type and Tg rats. These results support the essential role of hCRM1 in proper HTLV-1 replication and suggest the importance of this Tg rat as an animal model for HTLV-1.<\/jats:p>","DOI":"10.1128\/jvi.02811-06","type":"journal-article","created":{"date-parts":[[2007,3,15]],"date-time":"2007-03-15T00:10:48Z","timestamp":1173917448000},"page":"5908-5918","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Enhanced Replication of Human T-Cell Leukemia Virus Type 1 in T Cells from Transgenic Rats Expressing Human CRM1 That Is Regulated in a Natural Manner"],"prefix":"10.1128","volume":"81","author":[{"given":"Ryo","family":"Takayanagi","sequence":"first","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eizaburo","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Hakata","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Komoda","sequence":"additional","affiliation":[{"name":"Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka 569-1125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka 569-1125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Tsunetsugu-Yokota","sequence":"additional","affiliation":[{"name":"Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Shida","sequence":"additional","affiliation":[{"name":"Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.4.1195"},{"key":"e_1_3_2_3_2","first-page":"86","volume":"76","year":"1985","unstructured":"Akagi, T., I. 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