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.
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.
Takayanagi
Ryo
R
Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Ohashi
Takashi
T
Yamashita
Eizaburo
E
Kurosaki
Yohei
Y
Tanaka
Kumiko
K
Hakata
Yoshiyuki
Y
Komoda
Yasumasa
Y
Ikeda
Satoru
S
Tsunetsugu-Yokota
Yasuko
Y
Tanaka
Yuetsu
Y
Shida
Hisatoshi
H
D000818:Animals; D030801:Animals, Genetically Modified; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D028884:Karyopherins / Q000096:biosynthesis / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000821:virology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication / Q000502:physiology*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein