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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

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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)

Submitter: 志田 壽利

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