This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takayanagi, R.
Right arrow Articles by Shida, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takayanagi, R.
Right arrow Articles by Shida, H.

 Previous Article  |  Next Article 

Journal of Virology, June 2007, p. 5908-5918, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02811-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Ryo Takayanagi,1 Takashi Ohashi,1 Eizaburo Yamashita,2 Yohei Kurosaki,1 Kumiko Tanaka,1 Yoshiyuki Hakata,1,{dagger} Yasumasa Komoda,3 Satoru Ikeda,3 Yasuko Tsunetsugu-Yokota,4 Yuetsu Tanaka,5 and Hisatoshi Shida1*

Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815,1 Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto,2 Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka 569-1125,3 Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640,4 Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan5

Received 20 December 2006/ Accepted 5 March 2007

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.

* Corresponding author. Mailing address: Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan. Phone and fax: 81-11-706-7543. E-mail: hshida{at}igm.hokudai.ac.jp

{triangledown} Published ahead of print on 14 March 2007.

{dagger} Present address: Department of Microbiology, New York University School of Medicine, 522 First Avenue, New York, NY 10016.

Journal of Virology, June 2007, p. 5908-5918, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02811-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»