1997 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	07044212
Research Institution	Hokkaido University
Principal Investigator	生田和良北海道大学, 免疫科学研究所, 教授 (60127181)
Co-Investigator(Kenkyū-buntansha)	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
Keywords	HIV-1 / AIDS / clade B / clade E / アポトーシス / Nef / 潜伏感染 / タイ
Research Abstract	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。

Research Products

(26 results)

All Other

All Publications (26 results)

[Publications] Goto, T.,: "The life cycle of human immunodeficiency virus type 1(review)." Micron. (in press).
[Publications] Tobiume, M.: "Dependence of host cell cycle for activation of HIV-1 gene expression from latency." J.Gen.Virol.(in press).
[Publications] Kobayashi, T.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. (in press).
[Publications] Iwahashi, K.: "Positive and negative sydromes,and Borna disease virus(BDV)infection in schizophrenia." Neuropsychobiology. (in press).
[Publications] 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)
[Publications] Hagiwara, K.: "High prevalence of Borna disease virus infection in healthy sheep in Japan." Ciln.Diagn.Lab.Immunol.4・3. 339-344 (1997)
[Publications] Fujiwara, S.: "Microplate hybridizatation for Borna disease virus RNA in human peripheral blood mononuclear cells." Ciln.Diagn.Lab.Immunol.4・3. 387-391 (1997)
[Publications] Takahashi, H.: "Higher prevalence of Borna disease virus infection in blood donors living near thoroughbred horse farms." J.Med.Virol.52. 330-335 (1997)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Haga, S.: "Detection of Borna disease virus genome in normal human brain tissue." Brain Res.770. 307-309 (1997)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Ohagenhagen, A.: "The morphology of the immature HIV-1 virion." Virology. 228. 112-114 (1997)
[Publications] Nakaya, T.: "Inhibition of HIV-1 replication by targeting the Rev protein." Leukemia. 11・3. 134-137 (1997)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Hirayama, J.: "Photoinactivation of virus infectivity by hypocrellin A." Photochem.& Photobiol.66. 697-700 (1997)
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

生田 和良 北海道大学, 免疫科学研究所, 教授 (60127181)

Research Products

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

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

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

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

[Publications] 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)

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

生田和良北海道大学, 免疫科学研究所, 教授 (60127181)