1997 年度実績報告書

エイズ病態に関する不完全ヒト免疫不全ウィルスの評価

研究課題

研究課題/領域番号	07044212
研究機関	北海道大学
研究代表者	生田和良北海道大学, 免疫科学研究所, 教授 (60127181)
研究分担者	亀岡正典奈良県立医科大学, 助手 (60281838) 中屋隆明北海道大学, 免疫科学研究所, 助手 (80271633) AUWANIT Watt Health Science Research Institute NIH, Senior Res LUFTIG Ronal Louisiana State University, Medical Cente, Professor JONES Ian M. Natural Environment Research Council, Ins, Project Le
キーワード	HIV-1 / AIDS / clade B / clade E / アポトーシス / Nef / 潜伏感染 / タイ
研究概要	HIVの感染からAIDS発病まで、約10年の無症候期を経る。最近の知見から、血液中ウィルス負荷のレベルが病態と密接に相関することが明らかにされている。また、カクテル療法によりこの血液中ウイルス負荷の顕著な低下が可能となった。しかし、このカクテル療法でも、有効性が確認できるのは短期生存型のウイルス産生細胞由来ウイルスに対してであり、長期生存型の潜伏感染細胞から活性化されたウイルスに対しての有効性は低い。私たちは、HIV感染の引き起こす病態関連機序として、Nef蛋白が潜伏から活性化する機能を見いだし、またウイルス非感染T細胞のアポトーシス誘導機序を明らかにした。これらの結果は、欧米諸国やわが国に蔓延しているB型 HIVを用いて解析されてきたものである。一方、タイを初め東南アジアで蔓延しているウイルスはE型HIVである。そこで、これらの現象について実際のHIV感染者における普遍性を検討する目的で、HIV E型ウイルスの解析を中心に行った。タイE型の全遺伝子配列は、1996年に初めて報告されたが、これらの遺伝子配列に従って作製したプライマーを用いても、血清学的に判定されたE型キャリア由来末梢血細胞内にHIV遺伝子をPCR増幅できない場合が多く、さらに変異が進んでいると考えられた。実際、nef遺伝子配列においても、今回のサンプル〈タイのキャリア由来E型2株とB型2株)では、上記論文に使用されたE型ウイルスに比ベ、genetic variabilityがE型2株間で6.43%、E型とB型間は〜13%と、変異がかなり進んでいることが判明した。実際、B型Nefに対して分離した13個のマウス単クローン抗体のいずれもタイE型Nefとは交差しなかった。一方、アポトーシス誘導に関しては、B型ウィルスで見られていた現象が実際に生体内(E型感染者であっても)で起こっていることが確認できた。

研究成果

(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Goto, T.,: "The life cycle of human immunodeficiency virus type 1(review)." Micron. (in press).
[文献書誌] Tobiume, M.: "Dependence of host cell cycle for activation of HIV-1 gene expression from latency." J.Gen.Virol.(in press).
[文献書誌] Kobayashi, T.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. (in press).
[文献書誌] Iwahashi, K.: "Positive and negative sydromes,and Borna disease virus(BDV)infection in schizophrenia." Neuropsychobiology. (in press).
[文献書誌] Fujinaga, K.: "Generation of endogenous tumour necrosis factor-a in MOLT-4 cells during the acute replicationphase of human immunodeficiency virus type 1 determines the subsequent latent infection." J.Gen.Virol.79. 221-229 (1998)
[文献書誌] Hagiwara, K.: "High prevalence of Borna disease virus infection in healthy sheep in Japan." Ciln.Diagn.Lab.Immunol.4・3. 339-344 (1997)
[文献書誌] Fujiwara, S.: "Microplate hybridizatation for Borna disease virus RNA in human peripheral blood mononuclear cells." Ciln.Diagn.Lab.Immunol.4・3. 387-391 (1997)
[文献書誌] Takahashi, H.: "Higher prevalence of Borna disease virus infection in blood donors living near thoroughbred horse farms." J.Med.Virol.52. 330-335 (1997)
[文献書誌] Shoya, Y.: "Amplification of a full-length Borna disease virus(BDV)cDNA from total RNA of cells persistently infected with BDV." Microbiol.Immunol.41. 481-486 (1997)
[文献書誌] Hagiwara, K.: "Demonstration of Borna disease virus(BDV) in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs." Med.Microbiol.Immunol.186. 19-24 (1997)
[文献書誌] Iwahashi, K.: "Clinical investigation of the relationship between Borna disease virus(BDV) infection and schizophrenia in 67 patients in Japan." Acta Psychiatr.Scand.96. 412-415 (1997)
[文献書誌] Haga, S.: "Detection of Borna disease virus genome in normal human brain tissue." Brain Res.770. 307-309 (1997)
[文献書誌] Kameoka, M.: "Protease-defective,gp120-containing humanimmunodeficiency virus type 1 particles induce apoptosis more effciently than does wild-type virus or recombinant gp120 protein in healthy donor-derived peripherl blood T cells." J.Clin.Microbiol.35. 41-47 (1997)
[文献書誌] Nakaya, T.: "Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory function of human immunodeficiency virus type 1 Rev protein" Antimicrob.Agents.Chemother.41. 319-325 (1997)
[文献書誌] Bahmani, M.K.: "Production of doughnut-shaped,protease-defective particles from a human T cell clone carrying a provirus with specific mutation in the env,pol,vpr,and nef genes" AIDS Res.Hum.Retrov.13. 523-526 (1997)
[文献書誌] Zheng, Y.-H.: "Insertions,duplications and substitutions in restricted gp90 regions of equine infectious anemia virus occurred during febrile episodes in an experimentally infected horse." J.Gen.Virol.78. 803-820 (1997)
[文献書誌] Nakamura, Y.: "A chain section containing epitopes for cytotoxic T,B and helper T cells within a highly conserved region found in the human immunodeficiency virus type 1 Gag Protein." Vaccine. 15・5. 489-496 (1997)
[文献書誌] Zhong, Q.: "A clearer distinction between HIV-1 paired isolates from peripheral blood mononuclear cells of asymptomatic carriers with and without CD8+T-cells at nef rather than env V3 loci." Vaccine. 15・5. 497-510 (1997)
[文献書誌] Zheng, Y.-H.: "In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain." J.Virol.71・7. 5031-5039 (1997)
[文献書誌] Ohagenhagen, A.: "The morphology of the immature HIV-1 virion." Virology. 228. 112-114 (1997)
[文献書誌] Nakaya, T.: "Inhibition of HIV-1 replication by targeting the Rev protein." Leukemia. 11・3. 134-137 (1997)
[文献書誌] Tokunaga, K.: "Growth ability of auxiliary gene mutants of human immunodeficiency virus type 1 and 2 in unstimulated peripheral blood mononuclear cells." Arch.Virol.142・1. 177-181 (1997)
[文献書誌] Kameoka, M.: "Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+killer cells in a small subset, leading to induction of apoptosis in bystander cells." Int.Immunol.9・10. 1453-1462 (1997)
[文献書誌] Watanabe, H.: "A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef." Biochem.Biophys.Res.Commun.238. 234-239 (1997)
[文献書誌] Hirayama, J.: "Photoinactivation of virus infectivity by hypocrellin A." Photochem.& Photobiol.66. 697-700 (1997)
[文献書誌] Ikuta, K.: "AIDS pathogenesis: the role of accessory gene mutations, leading to formation of long-lived persistently infected cells ang/or apoptosis-inducing HIV-1 particles." Virus Res.52. 145-156 (1997)

1997 年度 実績報告書

エイズ病態に関する不完全ヒト免疫不全ウィルスの評価

研究代表者

生田 和良 北海道大学, 免疫科学研究所, 教授 (60127181)

研究成果

[文献書誌] Goto, T.,: "The life cycle of human immunodeficiency virus type 1(review)." Micron. (in press).

[文献書誌] Tobiume, M.: "Dependence of host cell cycle for activation of HIV-1 gene expression from latency." J.Gen.Virol.(in press).

[文献書誌] Kobayashi, T.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. (in press).

[文献書誌] Iwahashi, K.: "Positive and negative sydromes,and Borna disease virus(BDV)infection in schizophrenia." Neuropsychobiology. (in press).

[文献書誌] Fujinaga, K.: "Generation of endogenous tumour necrosis factor-a in MOLT-4 cells during the acute replicationphase of human immunodeficiency virus type 1 determines the subsequent latent infection." J.Gen.Virol.79. 221-229 (1998)

[文献書誌] Hagiwara, K.: "High prevalence of Borna disease virus infection in healthy sheep in Japan." Ciln.Diagn.Lab.Immunol.4・3. 339-344 (1997)

[文献書誌] Fujiwara, S.: "Microplate hybridizatation for Borna disease virus RNA in human peripheral blood mononuclear cells." Ciln.Diagn.Lab.Immunol.4・3. 387-391 (1997)

[文献書誌] Takahashi, H.: "Higher prevalence of Borna disease virus infection in blood donors living near thoroughbred horse farms." J.Med.Virol.52. 330-335 (1997)

[文献書誌] Shoya, Y.: "Amplification of a full-length Borna disease virus(BDV)cDNA from total RNA of cells persistently infected with BDV." Microbiol.Immunol.41. 481-486 (1997)

[文献書誌] Hagiwara, K.: "Demonstration of Borna disease virus(BDV) in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs." Med.Microbiol.Immunol.186. 19-24 (1997)

[文献書誌] Iwahashi, K.: "Clinical investigation of the relationship between Borna disease virus(BDV) infection and schizophrenia in 67 patients in Japan." Acta Psychiatr.Scand.96. 412-415 (1997)

[文献書誌] Haga, S.: "Detection of Borna disease virus genome in normal human brain tissue." Brain Res.770. 307-309 (1997)

[文献書誌] Kameoka, M.: "Protease-defective,gp120-containing humanimmunodeficiency virus type 1 particles induce apoptosis more effciently than does wild-type virus or recombinant gp120 protein in healthy donor-derived peripherl blood T cells." J.Clin.Microbiol.35. 41-47 (1997)

[文献書誌] Nakaya, T.: "Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory function of human immunodeficiency virus type 1 Rev protein" Antimicrob.Agents.Chemother.41. 319-325 (1997)

[文献書誌] Bahmani, M.K.: "Production of doughnut-shaped,protease-defective particles from a human T cell clone carrying a provirus with specific mutation in the env,pol,vpr,and nef genes" AIDS Res.Hum.Retrov.13. 523-526 (1997)

[文献書誌] Zheng, Y.-H.: "Insertions,duplications and substitutions in restricted gp90 regions of equine infectious anemia virus occurred during febrile episodes in an experimentally infected horse." J.Gen.Virol.78. 803-820 (1997)

[文献書誌] Nakamura, Y.: "A chain section containing epitopes for cytotoxic T,B and helper T cells within a highly conserved region found in the human immunodeficiency virus type 1 Gag Protein." Vaccine. 15・5. 489-496 (1997)

[文献書誌] Zhong, Q.: "A clearer distinction between HIV-1 paired isolates from peripheral blood mononuclear cells of asymptomatic carriers with and without CD8+T-cells at nef rather than env V3 loci." Vaccine. 15・5. 497-510 (1997)

[文献書誌] Zheng, Y.-H.: "In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain." J.Virol.71・7. 5031-5039 (1997)

[文献書誌] Ohagenhagen, A.: "The morphology of the immature HIV-1 virion." Virology. 228. 112-114 (1997)

[文献書誌] Nakaya, T.: "Inhibition of HIV-1 replication by targeting the Rev protein." Leukemia. 11・3. 134-137 (1997)

[文献書誌] Tokunaga, K.: "Growth ability of auxiliary gene mutants of human immunodeficiency virus type 1 and 2 in unstimulated peripheral blood mononuclear cells." Arch.Virol.142・1. 177-181 (1997)

[文献書誌] Kameoka, M.: "Exposure of resting peripheral blood T cells to HIV-1 particles generates CD25+killer cells in a small subset, leading to induction of apoptosis in bystander cells." Int.Immunol.9・10. 1453-1462 (1997)

[文献書誌] Watanabe, H.: "A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef." Biochem.Biophys.Res.Commun.238. 234-239 (1997)

[文献書誌] Hirayama, J.: "Photoinactivation of virus infectivity by hypocrellin A." Photochem.& Photobiol.66. 697-700 (1997)

[文献書誌] Ikuta, K.: "AIDS pathogenesis: the role of accessory gene mutations, leading to formation of long-lived persistently infected cells ang/or apoptosis-inducing HIV-1 particles." Virus Res.52. 145-156 (1997)

1997 年度実績報告書

生田和良北海道大学, 免疫科学研究所, 教授 (60127181)