1999 Fiscal Year Annual Research Report

麻疹ウイルスによる宿主免疫抑制の分子機構

Research Project

Project/Area Number	10470083
Research Institution	Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
Principal Investigator	瀬谷司大阪府立成人病センター, 第6部, 部長 (10301805)
Co-Investigator(Kenkyū-buntansha)	櫨木修広島大学, 医学部・総合薬学科・薬効解析化学講座, 教授
Keywords	麻疹ウイルス / ヒトCD46 / シグナル伝達分子 / SHP-1 / CD9 / α_3β_1インテグリン / Moesin / 免疫抑制
Research Abstract	1.ヒトマクロファージは活性化ステージ(例えばGM-CSF6日間培養)に応じてCD46-SHP1複合体を形成する。 2.CD46-SHP1複合体にはCD9、α_3β_1インテグリンが共存する。 3.この複合体形成時に麻疹ウイルス感染性が極めて高くなり、合胞体形成を誘起する。 4.NO産生、IL-12産生の増強もCD46複合体形成時のヒトマクロファージで見られる。ただし、ウィルス株特異性があり、KO株のみがこの細胞応答を惹起する。CD46のdown-regulationもKOのみでおこる。 5.KO株のHproteinのアミノ酸、451Ala,473Leuがこの細胞応答に重要である。V451A,I473Lの通常株ではNO産生もIL-12産生も誘起しない。以上の結果と麻疹ウィルスによる一過性免疫抑制の関連は未だ直接証明が得られていないが、i)CD46がシグナル伝達レセプターとして機能すること、ii)麻疹ウィルスは株に依存してマクロファージ系の機能を変調せしめること、が明らかになった。以上の点をKurita-Taniguchi,Seya et.al.(J.Immunol,in press)とHazeki,Seya et.al.(Biuochem.J.,submitted)に投稿中である。

Research Products
(8 results)

All Other

All Publications (8 results)

[Publications] Doi, Y., T. Seya et. al.: "Moesin is not a receptor for measles virus entry into mouse embryonic stem cells"J. Virol.. 72. 1586-1592 (1998)
[Publications] Murakami, Y., T. Seya et. al.: "Molecular cloning of membrane cofactor protein (MCP. CD46) on B95a cell an Epstein-Barr virus-transformed marmoset B cell line"Biochem. J.. 330. 1351-1359 (1998)
[Publications] Sakata, H., T. Seya et. al.: "A Japanese wild-type measles virus strain including predominant early down-regulation of CD46"Biol. Pharmac. Bull. 21. 1121-1127 (1998)
[Publications] Murakami, Y., T. Seya et. al.: "Effect of mutations at the residues R25 D27 P69 and N70 of B95a-MCP on receptor activities for the measles virus Nagahata wild-type strain and CAM vaccine strain"Int. J. Mol. Med.. 3. 25-32 (1999)
[Publications] Shida, K., T. Seya et. al.: "The 3-UT of the ubiquitous message of human CD46 confers selective suppression of protein production in murine cells"Eur. J. Immunol.. 29. 3603-3608 (1999)
[Publications] Kurita-Taniguchi, M. T. Seya et. al.: "Activation of human macrophages through CD46 (measles virus receptor) : Production of IL-12 p40 and nitric oxygen in association re*ment of *-1 to CD46"J. Immunol.. (in press).
[Publications] Seya, T., et al.: "CD46 (membrane cofactor protein (MCP) of complement, measles virus receptor) : structural and functional divergence among species"Int. J. Mol. Med.. 7 (1998)
[Publications] Seya, T., A. Hirano et al.: "Human membrane cofactor protein of complement (CD46) : multiple isoforms and functions"Int. J. Biochem. Cell Biol.. 5 (1999)

1999 Fiscal Year Annual Research Report

麻疹ウイルスによる宿主免疫抑制の分子機構

Principal Investigator

瀬谷 司 大阪府立成人病センター, 第6部, 部長 (10301805)

Research Products

[Publications] Doi, Y., T. Seya et. al.: "Moesin is not a receptor for measles virus entry into mouse embryonic stem cells"J. Virol.. 72. 1586-1592 (1998)

[Publications] Murakami, Y., T. Seya et. al.: "Molecular cloning of membrane cofactor protein (MCP. CD46) on B95a cell an Epstein-Barr virus-transformed marmoset B cell line"Biochem. J.. 330. 1351-1359 (1998)

[Publications] Sakata, H., T. Seya et. al.: "A Japanese wild-type measles virus strain including predominant early down-regulation of CD46"Biol. Pharmac. Bull. 21. 1121-1127 (1998)

[Publications] Murakami, Y., T. Seya et. al.: "Effect of mutations at the residues R25 D27 P69 and N70 of B95a-MCP on receptor activities for the measles virus Nagahata wild-type strain and CAM vaccine strain"Int. J. Mol. Med.. 3. 25-32 (1999)

[Publications] Shida, K., T. Seya et. al.: "The 3-UT of the ubiquitous message of human CD46 confers selective suppression of protein production in murine cells"Eur. J. Immunol.. 29. 3603-3608 (1999)

[Publications] Kurita-Taniguchi, M. T. Seya et. al.: "Activation of human macrophages through CD46 (measles virus receptor) : Production of IL-12 p40 and nitric oxygen in association re*ment of *-1 to CD46"J. Immunol.. (in press).

[Publications] Seya, T., et al.: "CD46 (membrane cofactor protein (MCP) of complement, measles virus receptor) : structural and functional divergence among species"Int. J. Mol. Med.. 7 (1998)

[Publications] Seya, T., A. Hirano et al.: "Human membrane cofactor protein of complement (CD46) : multiple isoforms and functions"Int. J. Biochem. Cell Biol.. 5 (1999)

瀬谷司大阪府立成人病センター, 第6部, 部長 (10301805)

[Publications] Kurita-Taniguchi, M. T. Seya et. al.: "Activation of human macrophages through CD46 (measles virus receptor) : Production of IL-12 p40 and nitric oxygen in association rement of -1 to CD46"J. Immunol.. (in press).