2006 Fiscal Year Final Research Report Summary
Human CRM1 expressing small animal model for HIV-1/HTLV-1 infections
| Project/Area Number |
17390131
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SHIDA Hisatoshi Hokkaido Univ., Institute for Genetic Medicine, Professor, 遺伝子病制御研究所, 教授 (00144395)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Takashi Hokkaido Univ., Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (10282774)
KIDOKORO Minoru National Institute for Infectious Disease, Third Department of Virology, Principal investigator, ウイルス第三部, 主任研究員 (00370958)
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| Project Period (FY) |
2005 – 2006
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| Keywords | HIV / HTLV-1 / rat model |
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| Research Abstract |
It is very useful to develop therapeutic and prophylactic means if HIV and HTLV-1 can infect to rats, because rats can be genetically manipulated and inbred strains have been established. In this project we are going to examine the steps in the replication cycle of HIV in rat epithelial, T cells, and macrophages, and search the human enhancing factors and rat inhibitors on replication of HIV in rats. Then we will construct transgenic (Tg) and knockdown rats. We have already identified CRM1 as a restriction factor between human and rats, and constructed human CRM1 expressing Tg rats. Thus we also examine the efficacy of replication of HTLV-1 in these rats.
We obtained the following results.
1.There are inhibitor(s), which work in concert with cyclophilin A during the penetration steps of HIV infection process in rat T cells but not in macrophages.
2.Expression of human CRM1 and cyclinT1 augments the replication of HIV-1 more than 100 fold.
3.Highly infectious HIV is produced in rat epithelial cells but not in T cells.
4.We constructed human CD4/CCR5/CXCR4/CRM1/CyclinTl expressing rats.
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 Hay-1 were similar to those produced by human T cells. We also observed enhancement of the dissemination of HTLV-1 to thymus in the Tg rats after intraperitoneal inoculation, although the proviral loads were low both in wild type and the 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.
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[Journal Article] SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.2007
Author(s)
Masahiro Kitabatake, Shingo Inoue, Fumihiko Yasui, Shoji Yokochi, Masaaki, Arai, Kouichi Morita, Hisatoshi Shida, Minoru Kidokoro, Fukashi Murai, Mai, Quynh Le, Kouji Matsushima, Michinori Kohara
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Journal Title
Vaccine 25
Pages: 630-637
Description
「研究成果報告書概要(欧文)」より
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