1999 Fiscal Year Annual Research Report

エイズ制御のための基礎研究柱2.HIV感染症の病態と免疫

Research Project

Project/Area Number	10180102
Research Institution	Kyoto University
Principal Investigator	内山卓京都大学, 医学研究科, 教授 (80151900)
Co-Investigator(Kenkyū-buntansha)	高橋秀実日本医科大学, 医学部, 教授 (40221361) 清野宏大阪大学, 微生物病研究所, 教授 (10271032) 長澤丘司大阪府立母子保健総合医療センター研究所, 部長 (80281690) 小柳義夫東北大学, 医学系研究科, 教授 (80215417) 滝口雅文熊本大学, エイズ学研究センター, 教授 (00183450)
Keywords	HIV / gp120 / CXCR4 / SDF-1 / CTL / 粘膜免疫
Research Abstract	内山は、NL4-3 gp120のV3領域をSDF-1、endothelin、またはANPで置換したキメラenvをもったpseudotyped virusを調製して、これらのウイルスがそれぞれ上記リガンドに対応する受容体を発現した細胞に感染しうることを示し、ウイルス侵入におけるV3領域と細胞膜分子の結合の意義を明確にした。長沢は、CXCR4欠損マウスの胎児肝造血細胞を致死量放射線を照射したLy5.1アロタイプの成体マウスに移植する実験を行い、SDF-1/CXCR4の作用が成体個体の骨髄初期分化に特異的かつ必須であることを明らかにした。清野は、Fusogenic liposomeをキャリアーに用いてHIV gp160でC57BL/6マウスを経鼻免疫すると、p160単独で免疫した場合に比べて高い抗原特異的抗体産生が誘導され、脾臓、鼻腔粘膜固有層、小腸粘膜固有層、膣においてgp160特異的抗体産生細胞の強い誘導が認められることを示した。高橋は長期未発症の発症遅延に関わる感染制御因子を追跡し、クラスIMHC拘束性CD8^+CTLと非拘束性NK細胞の双方が関与すること、また、こうした細胞性免疫や特異抗体産生を制御するヘルパーT細胞の認識エピトープがHIVのV3領域などの高頻度可変部領域であることを確認した。滝口は6種類のCTLエピトープペプチドを用いてHLA-B^*3501テトラマーを作製してHLA-B35をもったHIV-1感染者末梢血単核球のHIV-1特異的CD8^+T細胞を検出する手技を確立し、HAART治療前後での比較検討の結果、ウイルスRNAの低下とともにテトラマー結合CD8^+T細胞の数が減少することを観察した。小柳はHIV感染急性期患者検体から限界希釈法にて得た分離株の解析を通じて、ウイルスが初感染時においても比較的に多様性に富んでいることとX4ウイルスの出現に一致して急速な病状進行がみられることを明らかにした。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Isaka , Y.: "Small Amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5"Virol. 264. 237-243 (1999)
[Publications] Nagasawa, T.: "A CXC chemokine SDF-1/PBSF : A ligand for a HIV coreceptor, CXCR4"Adv. Immunol.. 71. 211-228 (1999)
[Publications] Kawabata, K.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc. Natl. Acad. Sci. USA. 96. 5663-5667 (1999)
[Publications] McGhee, J. R.: "Mucosal Th1-versus Th2-type responses for antibody or cell mediated immunity to SIV rhesus macaques"J. Infect. Dise.. 179. 5480-5484 (1999)
[Publications] Ohashi, T.: "Role of class I major histocompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 replication CD8^+ T lymphocytes"J. Gen. Virol.. 80. 209-216 (1999)
[Publications] Tomiyama, H.: "Identification of Multiple HIV-1 Epitopes presented by HLA-B*5101 Molecules"Hum. Immunol.. 60. 177-186 (1999)
[Publications] Tomiyama, H.: "Cytotoxic T-lymphocyte recognition of HLA-B*5101-restricted HIV-1 Rev epitope which is naturally processed in HIV-1 infected cells"AIDS. 13. 861-863 (1999)
[Publications] Kawana, A.: "Accumulation of specific amino acid substitutions in HLA-B35-restricted human immunodeficiency virus type-1 cytotoxic T lymphocyte epitopes"AIDS. Res. Hum. Retroviruses.. 12. 1099-1107 (1999)
[Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition of HIV-1 Pol protein"AIDS. 13. 1413-1414 (1999)
[Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition for a novel epitope derived from the HIV-1 Env protein"AIDS. 13. 2597-2599 (1999)
[Publications] Suzuki, Y.: "Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine induced CD4^+ T-helper 1 (Th1)-and Th2-type conditions"J Virol. 73. 316-324 (1999)
[Publications] Murakami, T.: "Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 (HIV-1) infection"J Virol. 73. 7489-7496 (1999)
[Publications] Ichiyama, K.: "Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library : comparison with ELISA using synthetic peptides"Viral Immunol. 12. 57-66 (1999)
[Publications] Maeda, N.: "Acquisition of HIV-1 resistance by β-chemokine-producing CD4+ T cells"AIDS Res Hum Retroviruses. 15. 1453-1460 (1999)
[Publications] Takahashi, K.: "Structural requirement for the two-step dimerization of human immunodeficiency virus type-1 genome"RNA. (in press).
[Publications] Momoi, Y.: "Pertusis toxin enhances human immunodefieicncy virus-1 replication"AIDS Res Hum Retroviruses. (in press).
[Publications] Chiaba, M.: "Recombinant vaccinia virus expressing an immunodominant epitope of HIV-1 envelope protein within an influenza hemagglutinin cassette predominantly prime epitope-specific CD8+ CTL"Arch. Virol.. 144. 1469-1485 (1999)

1999 Fiscal Year Annual Research Report

エイズ制御のための基礎研究 柱2.HIV感染症の病態と免疫

Principal Investigator

内山 卓 京都大学, 医学研究科, 教授 (80151900)

Research Products

[Publications] Isaka , Y.: "Small Amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5"Virol. 264. 237-243 (1999)

[Publications] Nagasawa, T.: "A CXC chemokine SDF-1/PBSF : A ligand for a HIV coreceptor, CXCR4"Adv. Immunol.. 71. 211-228 (1999)

[Publications] Kawabata, K.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc. Natl. Acad. Sci. USA. 96. 5663-5667 (1999)

[Publications] McGhee, J. R.: "Mucosal Th1-versus Th2-type responses for antibody or cell mediated immunity to SIV rhesus macaques"J. Infect. Dise.. 179. 5480-5484 (1999)

[Publications] Ohashi, T.: "Role of class I major histocompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 replication CD8^+ T lymphocytes"J. Gen. Virol.. 80. 209-216 (1999)

[Publications] Tomiyama, H.: "Identification of Multiple HIV-1 Epitopes presented by HLA-B*5101 Molecules"Hum. Immunol.. 60. 177-186 (1999)

[Publications] Tomiyama, H.: "Cytotoxic T-lymphocyte recognition of HLA-B*5101-restricted HIV-1 Rev epitope which is naturally processed in HIV-1 infected cells"AIDS. 13. 861-863 (1999)

[Publications] Kawana, A.: "Accumulation of specific amino acid substitutions in HLA-B35-restricted human immunodeficiency virus type-1 cytotoxic T lymphocyte epitopes"AIDS. Res. Hum. Retroviruses.. 12. 1099-1107 (1999)

[Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition of HIV-1 Pol protein"AIDS. 13. 1413-1414 (1999)

[Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition for a novel epitope derived from the HIV-1 Env protein"AIDS. 13. 2597-2599 (1999)

[Publications] Suzuki, Y.: "Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine induced CD4^+ T-helper 1 (Th1)-and Th2-type conditions"J Virol. 73. 316-324 (1999)

[Publications] Murakami, T.: "Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 (HIV-1) infection"J Virol. 73. 7489-7496 (1999)

[Publications] Ichiyama, K.: "Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library : comparison with ELISA using synthetic peptides"Viral Immunol. 12. 57-66 (1999)

[Publications] Maeda, N.: "Acquisition of HIV-1 resistance by β-chemokine-producing CD4+ T cells"AIDS Res Hum Retroviruses. 15. 1453-1460 (1999)

[Publications] Takahashi, K.: "Structural requirement for the two-step dimerization of human immunodeficiency virus type-1 genome"RNA. (in press).

[Publications] Momoi, Y.: "Pertusis toxin enhances human immunodefieicncy virus-1 replication"AIDS Res Hum Retroviruses. (in press).

[Publications] Chiaba, M.: "Recombinant vaccinia virus expressing an immunodominant epitope of HIV-1 envelope protein within an influenza hemagglutinin cassette predominantly prime epitope-specific CD8+ CTL"Arch. Virol.. 144. 1469-1485 (1999)

エイズ制御のための基礎研究柱2.HIV感染症の病態と免疫

内山卓京都大学, 医学研究科, 教授 (80151900)