1994 Fiscal Year Annual Research Report

エイズ制圧へ向けての基礎研究柱2 HIVの生物学

Research Project

Project/Area Number	04269102
Research Institution	Tokyo Medical and Dental University
Principal Investigator	山本直樹東京医科歯科大学, 医学部, 教授 (00094053)
Co-Investigator(Kenkyū-buntansha)	星野洪郎群馬大学, 医学部, 教授 (00107434) 生田和良北海道大学, 免疫科学研究所, 教授 (60127181) 原田信志熊本大学, 医学部, 教授 (60173085)
Keywords	エイズ / HIV / 潜伏感染 / 持続感染 / 薬剤耐性 / トロピズム
Research Abstract	HIVと宿主の相互作用を主としてウイルス学的に研究し、各班員がそれぞれ以下の結果を得た。 HIV-1が感染していながらその発現はほとんどない単球・マクロファージ系の細胞株(J22HL-60、U1)を用いて、種々の刺激によるウイルスの誘導を行い、その機序解明を試みた。その結果、LPS誘導ではCD14、ジアシルグリセロールがまた、コレラ毒素と百日咳毒素でG蛋白が関与していることがわかった。またマイコプラスマからユニークなホスホコリン含有グリセロ糖脂質を見い出した。(山本) プロテアーゼ阻害剤(RPI312)を使用し耐性HIVを得た。この耐性HIVは、pol遺伝子の2082がA→Gと変異していた。184→Vのアミノ酸変化が起こり、そのため薬剤耐性となったと考えられた。またマイコプラブマ由来の逆転写酵素阻害物質を同定した。(原田) リンパ球およびマクロファージ系細胞におけるHIVの潜伏・持続感染成立機序は極めて多様であったが、特にMT-4細胞ではウイルスのアクセサリー遺伝子(vif,vpr)の変異(nonsense変異やmisalignment欠失など)に相関すること、またこの変異はnefの存在下でのみ起こることが明らかになった。(生田) CD4を発現するようにしたグリオーマ細胞を用い、新しい変異株の分離を試みた。GUN-1株より数種の変異株を分離した。また、分離した8つのHIV-1株を用い、新たにGUN-4およびGUN-7の変異株を分離し、V3領域のアミノ酸配列をDNAの塩基配列から推定し野性株と比較した。(星野)

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Chowdhury IH: "cAMP stimulates human immunodeficiency virus(HIV-1)from latently infected cells of monocyte-macrophage lineage:Synergism with TNF-α" Virology. 194. 345-349 (1993)
[Publications] Chowdhury IH: "Pertussis toxin inhibits induction of human immunodeficiency virus type 1 infected monocytes" Virology. 203. 378-383 (1994)
[Publications] Mastuda K: "Glycosphingolipid compositionsof human T-lymphotropic virus type 1(HTLV-1)and human immunodeficiency virus(HIV)-infected cell lines" Biochim Biophys Acta. 1168. 123-9 (1993)
[Publications] Matsuda K: "Occurrence of a novel glycolipid containing phosphocholine in HTLV-1-infected cells" Glycoconjugate J. 10. 340 (1993)
[Publications] Matsuda K: "Characterization of a novel phosphocoline-containing glycoglycerolipid from M.fermentans" J.Biol Chem. (in press).
[Publications] Nishida Y: "Synthesis and absolute configuration of 6-0-phosphocholine-α-D-glucopyranosyl glycerolipid isolated from HTLV-1-infected cell lines" Tetrahedron Lett. (in press).
[Publications] Chowdhury IH: "Mycoplasma stimulated HIV-1 expression from acutely-and dormantly-infected promonocyte/monoblastoid cell line" Arch Virol. (in press).
[Publications] EL-Farrash MA: "Generation and characterization of a human immunodeficiency virus type1(HIV-1)mutant resistant to an HIV-1 protease inhibitor" J Virol. 68. 233-239 (1994)
[Publications] Nishino Y: "Presistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus" J Gen Virol. 75. 2241-2251 (1994)
[Publications] Nakaya R: "Nonsense mutations in the vpr gene of HIV-1 carrier-derived peripheral blood mononuclear cells" FEBS Lett. 354. 17-22 (1994)
[Publications] Kimura T: "Amplification of superoxide anion generation in phagocytic cells by HIV-1 infection" FEBS Lett. 326. 232-236 (1993)
[Publications] Kameoka M: "Superoxide enhances the spread of HIV-1 infection by cell-to-cell transmission" FEBS Lett. 331. 182-186 (1993)
[Publications] Fujii Y: "Evidence for the role of human immunodeficiency virus type 1 Nef protein as a growth inhibitor to CD4+ T lymphocytes and for the blocking of the Nef function by anti-Nef antibodies" Vaccine. 11. 837-847 (1993)
[Publications] Fujii Y: "Expression of human immunodeficiency virus type 1 Nef antigen on the surface of acutely and persistently infected human T cells" Vaccine. 11. 1240-1246 (1993)
[Publications] Otake: "The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells" J Immunol. (in press).
[Publications] Shimizu SN: "Isolation and cheracterization of humman immunodeficiency virus type 1 variants infectious to brain-derived cells:detection of common point mutations in the V3 region of the env gene of the variants" J Virol. 239. 6130-6135 (1994)

1994 Fiscal Year Annual Research Report

エイズ制圧へ向けての基礎研究 柱2 HIVの生物学

Principal Investigator

山本 直樹 東京医科歯科大学, 医学部, 教授 (00094053)

Research Products

[Publications] Chowdhury IH: "cAMP stimulates human immunodeficiency virus(HIV-1)from latently infected cells of monocyte-macrophage lineage:Synergism with TNF-α" Virology. 194. 345-349 (1993)

[Publications] Chowdhury IH: "Pertussis toxin inhibits induction of human immunodeficiency virus type 1 infected monocytes" Virology. 203. 378-383 (1994)

[Publications] Mastuda K: "Glycosphingolipid compositionsof human T-lymphotropic virus type 1(HTLV-1)and human immunodeficiency virus(HIV)-infected cell lines" Biochim Biophys Acta. 1168. 123-9 (1993)

[Publications] Matsuda K: "Occurrence of a novel glycolipid containing phosphocholine in HTLV-1-infected cells" Glycoconjugate J. 10. 340 (1993)

[Publications] Matsuda K: "Characterization of a novel phosphocoline-containing glycoglycerolipid from M.fermentans" J.Biol Chem. (in press).

[Publications] Nishida Y: "Synthesis and absolute configuration of 6-0-phosphocholine-α-D-glucopyranosyl glycerolipid isolated from HTLV-1-infected cell lines" Tetrahedron Lett. (in press).

[Publications] Chowdhury IH: "Mycoplasma stimulated HIV-1 expression from acutely-and dormantly-infected promonocyte/monoblastoid cell line" Arch Virol. (in press).

[Publications] EL-Farrash MA: "Generation and characterization of a human immunodeficiency virus type1(HIV-1)mutant resistant to an HIV-1 protease inhibitor" J Virol. 68. 233-239 (1994)

[Publications] Nishino Y: "Presistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus" J Gen Virol. 75. 2241-2251 (1994)

[Publications] Nakaya R: "Nonsense mutations in the vpr gene of HIV-1 carrier-derived peripheral blood mononuclear cells" FEBS Lett. 354. 17-22 (1994)

[Publications] Kimura T: "Amplification of superoxide anion generation in phagocytic cells by HIV-1 infection" FEBS Lett. 326. 232-236 (1993)

[Publications] Kameoka M: "Superoxide enhances the spread of HIV-1 infection by cell-to-cell transmission" FEBS Lett. 331. 182-186 (1993)

[Publications] Fujii Y: "Evidence for the role of human immunodeficiency virus type 1 Nef protein as a growth inhibitor to CD4+ T lymphocytes and for the blocking of the Nef function by anti-Nef antibodies" Vaccine. 11. 837-847 (1993)

[Publications] Fujii Y: "Expression of human immunodeficiency virus type 1 Nef antigen on the surface of acutely and persistently infected human T cells" Vaccine. 11. 1240-1246 (1993)

[Publications] Otake: "The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells" J Immunol. (in press).

[Publications] Shimizu SN: "Isolation and cheracterization of humman immunodeficiency virus type 1 variants infectious to brain-derived cells:detection of common point mutations in the V3 region of the env gene of the variants" J Virol. 239. 6130-6135 (1994)

エイズ制圧へ向けての基礎研究柱2 HIVの生物学

山本直樹東京医科歯科大学, 医学部, 教授 (00094053)