Studies on the mechanism for HIV-1 Thai CRF01_AE-induced high apoptosis induction and the development of its control

• Project/Area Number: 17390135
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: IKUTA Kazuyoshi Osaka University, 微生物病研究所, 教授 (60127181)
• Co-Investigator(Kenkyū-buntansha): SAKUDO Akikazu 大阪大学, 微生物病研究所, 助教 (10397672) ; KAMEOKA Masanori 大阪大学, 微生物病研究所, 特任准教授 (60281838) ; SHOJI Sanae 大阪大学, 微生物病研究所, 特任研究員 (20397681)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,740,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥1,740,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
• Keywords: HIV / AIDS / CRF01_AE / アポトーシス / 重感染 / 組換え型 / ワクチン / HIV-1 / B型 / タイ / Env / Pol / 中和抗体 / プロテアーゼ阻害剤 / サブタイプB / CRF15 01B / 遺伝子変異 / 持続感染 / 組換え / vpu / CRFO1_AE / CD38 / RNF125 / CRF01-AE

Research Abstract

HIV-1は遺伝子変異を引き起こしやすく、これがHIV-1病態の大きな特徴となっており、根本的な治療法やワクチン開発ができない原因となっている。本研究では、HIV-1の病態機序解明およびglobal epitope誘導型ワクチン開発を目指して、タイ型(AE型)と欧米型(B型)間のウイルス学的な差異、組換え型出現機序、Env gp41を認識させやすいHIV-1の構築などにフォーカスした研究を行なった。

Research Products

• [Journal Article] Phenotypic studies on recombinant human immunodeficiency virus type 1 (HIV-1) containing CRF01_AE env gene derived from HIV-1-infected patient (2009)
  • Author(s): Utachee, P., Jinnopat, P., Isarangkura-Na-Ayuthaya, P., de Silva, U.C., Nakamura, S., Siripanyaphinyo, U., Wichukchinda, N., Tokunaga, K., Yasunaga, T., Sawanpanyalert, P., Ikuta, K., Auwanit, W., and Kameoka, M.
  • Journal Title: residing central Thailand. Microbes Infect 11 Pages: 2334-343
• [Journal Article] Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome (2008)
  • Author(s): Kitagawa, Y., Kameoka, M., Shoji-Kawata, S., Iwabu, Y., Mizuta, H., Tokunaga, K., Fujino, M., Natori, Y., Yura, Y., and Ikuta, K.
  • Journal Title: Virology 373 Pages: 171-180
• [Journal Article] Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination (2008)
  • Author(s): Iwabu, Y., Mizuta, H., Kawase, M., Kameoka, M., Goto, T., and Ikuta, K.
  • Journal Title: Microbes Infect 10 Pages: 504-513
• [Journal Article] An HIV clade B defective particle producing cell line (L-2) shows stability in its HIV mutated genome over 10 years (2008)
  • Author(s): Zhong, Q., Ikuta, K., and Luftig, R. B.
  • Journal Title: Current Topics in Virology 6 Pages: 15-24
• [Journal Article] Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination. (2008)
  • Author(s): Iwabu Y., et al.
  • Journal Title: Microbes Infect. 10 Pages: 504-513
  • Peer Reviewed
• [Journal Article] Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome. (2008)
  • Author(s): Kitagawa Y., et al.
  • Journal Title: Virology 373 Pages: 171-180
  • Peer Reviewed
• [Journal Article] Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination (2008)
  • Author(s): Iwabu, Y., et. al.
  • Journal Title: Microbes and Infection (In press)
  • Peer Reviewed
• [Journal Article] Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome. (2008)
  • Author(s): Kitagawa, Y., et. al.
  • Journal Title: Virology (In press)
  • Peer Reviewed
• [Journal Article] The RING finger ubiquitin ligase RNF125/TRAC-1 down-modulates HIV-1 replication in primary human peripheral blood mononuclear cells (2007)
  • Author(s): Shoji-Kawata, S., Zhong, Q., Kameoka, M., Iwabu, Y., Sapsutthipas, S., Luftig, R.B., and Ikuta, K.
  • Journal Title: Virology 368 Pages: 191-204
• [Journal Article] Aberrant life cycle of human immunodeficiency virus type 1 CRF15_01B-like clinical isolates from Thailand in human CD4^+T-cell lines. (2007)
  • Author(s): Warachit, J., et. al.
  • Journal Title: Microbes and Infection 9 Pages: 449-459
  • Peer Reviewed
• [Journal Article] Identification of the suppressive factors for human immunodeficiency virus type-1 replication using the siRNA mini-library directed against host cellular genes. (2007)
  • Author(s): Kameoka, M., et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 359 Pages: 729-734
  • Peer Reviewed
• [Journal Article] I The RING finger ubiquitin ligase RNF125/TRAC-1 down-modulates HIV-1 replication in primary human peripheral blood mononuclear cells. (2007)
  • Author(s): Shoji-Kawata, S., et. al.
  • Journal Title: Virology 368 Pages: 191-204
  • Peer Reviewed
• [Journal Article] Aberrant life cycle of human immunodeficiency virus type 1 CRF15_01B-like clinical isolates from Thailand in human CD4^+ T-cell lines. (2007)
  • Author(s): Warachit, J. et al.
  • Journal Title: Microbes and Infection (In press)
• [Journal Article] Superinfection of human immunodeficiency virus type 1 (HIV-1) to cell clone persistently infected with defective virus induces production of highly cytopathogenic HIV-1 (2006)
  • Author(s): Iwabu, Y., Goto, T., Tsuji, S., Warachit, J., Li, G.M., Shoji, S., Kameoka, M., Ikuta, K.
  • Journal Title: Microbes Infect 8 Pages: 1773-1782
• [Journal Article] Superinfection of human immunodeficiency virus type 1 (HIV-1) to cell clone persistently infected with defective virus induces production of highly cytopathogenic HIV-1. (2006)
  • Author(s): Iwabu, Y. et al.
  • Journal Title: Microbes and Infection 8 Pages: 1773-1882
• [Journal Article] Higher frequency of premature stop codon mutations at vpu gene of human immunodeficiency virus type 1 CRF01_AE compared with those of other subtypes (2005)
  • Author(s): Komoto, S., Tsuji, S., Lee, B.J., Iwabu, Y., Kojima, Y., Otake, T., Taniguchi, K., Ikuta, K.
  • Journal Title: Microbes Infect 7 Pages: 139-147
• [Journal Article] Different susceptibility of human immunodeficiency virus type 1 to Env gp41-derived synthetic peptides corresponding to the two heptad repeat regions (2005)
  • Author(s): Isarangkura, P.N.A., Li, G.M., Warachit, J., Iwabu, Y., Tsuji, S., Auwanit, W., Yamamoto, D., Goto, T., Hayashi, Y., Kiso, Y., Ikuta. K.
  • Journal Title: Microbes Infect 7 Pages: 356-364
• [Journal Article] Interleukin-4 upregulates T-tropic human immunodeficiency virus type 1 transcription in primary CD4^+ CD38^+ T-lymphocyte subset (2005)
  • Author(s): Li, Y.G., Iwabu, Y., Warachit, J., Kinomoto, M., Ibrahim, M.S., Tsuji, S., Mukai, T., Kameoka, M., Tokunaga, K., Sata, T., Ikuta, K.
  • Journal Title: Microbiol. Immunol 49 Pages: 155-165
  • NAID: 10014430004
• [Journal Article] Amino acid 36 in HIV-1 gp41 ectodomain control fusogenic activity : Implications for the molecular mechanism of viral escape from a fusion inhibitor (2005)
  • Author(s): Kinomoto, M., Yokoyama, M., Sato, H., Kojima, A., Kurata, T., Ikuta, K., Sata, T.,Tokunaga, K.
  • Journal Title: J. Virol 79 Pages: 5996-6003
• [Journal Article] Higher frequency of premature stop codon mutations at vpu gene of human immunodeficiency virus type 1 CRF01_AE compared with those of other subtypes (2005)
  • Author(s): Komoto, S. et al.
  • Journal Title: Microbes and Infaction 7 Pages: 139-147
• [Journal Article] Different susceptibility of human immunodeficiency virus type 1 to Env gp41-derived synthetic peptides corresponding to the two heptad repeat regions (2005)
  • Author(s): Isarangkura, P.N.A. et al.
  • Journal Title: Microbes and Infaction 7 Pages: 356-364
• [Journal Article] Interleukin-4 upregulates T-tropic human immunodeficiency virus type 1 transcription in primary CD4^+ CD38^+ T-lymphocyte subset (2005)
  • Author(s): Li, Y.G.et al.
  • Journal Title: Microbiol Immunel 49 Pages: 155-165
• [Journal Article] Amino acid 36 in HIV-1 gp41 ectodomain control fusogenic activity : Implications for the molecular mechanism of viral escape from a fusion inhibitor (2005)
  • Author(s): Kinomoto, M. et al.
  • Journal Title: Journal of Virology 79 Pages: 5996-6004
• [Journal Article] L^<565>M mutation in HIV-1 glycoprotein 41 stabilizes the coiled-coil structure. (2005)
  • Author(s): Yamamoto, D. et al.
  • Journal Title: Biochemical and Biophysical Research Communications 335 Pages: 112-116
• [Journal Article] A novel diagnostic method for human immunodeficiency virus type-1 in plasma by near-infrared spectroscopy (2005)
  • Author(s): Sakudo, A. et al.
  • Journal Title: Microbiol Immunel 49 Pages: 695-701
  • NAID: 10016568061
• [Journal Article] Poly(ADP-ribose)polymerase-1 is required for integration of the human immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and murine cells. (2005)
  • Author(s): Kameoka, M. et al.
  • Journal Title: Biochemical and Biophysical Research Communications 334 Pages: 412-417
• [Journal Article] Phenotypic studies on recombinant human immunodeficiency virus type 1 (HIV-1) containing CRF01_AE env gene derived from HIV-1-infected patient, residing in central Thailand.
  • Author(s): Utachee P., et al.
  • Journal Title: Microbes Infect. (In press)
  • Peer Reviewed
• [Journal Article] Genotypic Characterization of CRF01_AE env Genes Derived from Human Immunodeficiency Virus Type 1-Infected Patients Residing in Central Thailand.
  • Author(s): Utachee P., et al.
  • Journal Title: AIDS Res Hum Retroviruses (In press)
  • Peer Reviewed
• [Presentation] CRF01_AE 型Gagがプロテアーゼ阻害剤に対するウイルスの薬剤感受性を低下させる分子機構について (2008)
  • Author(s): 亀岡正典、Piyamat Jinnopat 、Panasda Isarangkura-N-A、Piraporn Utachee、北川友紀子、Udayanga Chandimal de Silva 、Uamporn Siripanyaphinyo、亀岡陽子、徳永研三、Pathom Sawanpanyalert 、WattanaAuwanit、生田和良
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] 高細胞融合能を示す非感染性HIV-1粒子のEnv gp41へのアミノ酸変異導入の効果 (2008)
  • Author(s): 川瀬倫子、水田浩之、川下理日人、鷹岡昭夫、長谷川紀昭、山田直子、生田和良
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] CRF01_AE型Gagがプロテアーゼ阻害剤に対するウイルスの薬剤感受性を低下させる分子機構について (2008)
  • Author(s): 亀岡 正典
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] HIV-1複製関連宿主因子として同定されたAP2αのウイルス増殖抑制機序の解析 (2007)
  • Author(s): 北川友紀子、亀岡正典、水田浩之、小路早苗、生田和良
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] HIV-1持続感染細胞への重感染により出現する組換えHIV-1 (2007)
  • Author(s): 水田浩之、川瀬倫子、岩部幸枝、亀岡正典、後藤俊幸、生田和良
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] タイ国サラブリー県の薬剤未治療HIV-1感染者から分離したHIV-1プロテアーゼの遺伝子型および表現型の解析 (2007)
  • Author(s): 亀岡正典、北川友紀子、川下理日人、徳永研三、生田和良
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Distinctive Biological Features of HIV Type 1 Subtype C Isolates of Indian Origin : Implications for Disease Progression (2007)
  • Author(s): Arias Juan Fernando、生田和良
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Distinctive Biological Features of HIV Type 1 Subtype C Isolates of Indian Origin: Implications for Disease Progression (2007)
  • Author(s): Arias Juan Fernando
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Book] 医科ウイルス学(高田賢蔵)(レトロウイルス科) (2009)
  • Author(s): 生田和良
  • Publisher: 南江堂
• [Remarks]
  • URL: http://virology.biken.osaka-u.ac.jp/index.html
• [Patent(Industrial Property Rights)] HIV転写制御因子
  • Inventor(s): 生田和良、小路早苗