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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
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 |
Authors: | Takayanagi, Ryo Browse this author | Ohashi, Takashi Browse this author | Yamashita, Eizaburo Browse this author | Kurosaki, Yohei Browse this author | Tanaka, Kumiko Browse this author | Hakata, Yoshiyuki Browse this author | Komoda, Yasumasa Browse this author | Ikeda, Satoru Browse this author | Tsunetsugu-Yokota, Yasuko Browse this author | Tanaka, Yuetsu Browse this author | Shida, Hisatoshi Browse this author →KAKEN DB |
Issue Date: | Jun-2007 |
Publisher: | American Society for Microbiology |
Journal Title: | Journal of Virology |
Volume: | 81 |
Issue: | 11 |
Start Page: | 5908 |
End Page: | 5918 |
Publisher DOI: | 10.1128/JVI.02811-06 |
PMID: | 17360758 |
Abstract: | Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). 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. |
Rights: | Copyright © 2007 American Society for Microbiology |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/27990 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 志田 壽利
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