HIV感染感受性に影響する宿主因子の解析

• Project/Area Number: 19041039
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 塩田 達雄 Osaka University, 微生物病研究所, 教授 (00187329)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥10,300,000 (Direct Cost: ¥10,300,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥5,200,000); Fiscal Year 2007: ¥5,100,000 (Direct Cost: ¥5,100,000)
• Keywords: HIV / ゲノム / SNP / コホート / アフリカ / カプシド / 三次元構造予測

Research Abstract

TRIM5αはHIV1型(HIV-1)増殖の初期過程をアカゲザル細胞中で阻害する因子として2004年に同定された。昨年度我々は、サルにおける増殖能が株により異なるHIV2型(HIV-2)とカニクイサルTRIM5αとの関係を調べ、HIV-2カプシドタンパク質(CA)の119番目のアミノ酸がプロリンの株はカニクイザルTRIM5αによる感染抑制を受けるが、アラニンまたはグルタミンの株はカニクイザルTRIM5αによる感染抑制を受けないことを明らかにした。この1アミノ酸のヒトTRIM5αによる感染阻害への影響を検討したところ、カニクイサルTRIM5αによる感染阻害を受けない株はヒトTRIM5αによる感染阻害も受けにくく、カニクイサルTRIM5αによる感染阻害を受ける株はヒトTRIM5αによっても感染が阻害されやすいことも示した。そこで本年度は、オックスフォード大学Rowland-Jones教授と共同で、西アフリカのHIV-2感染患者コホートの69名のCAのアミノ酸配列を調べた。その結果、血中ウイルス量の違いと有意な相関のあるアミノ酸変異が3カ所(119、159、178番目)見つかった。119番目のアミノ酸は、まさに我々がTRIM5αの感染阻害効果との関連を見いだした場所であり、ヒトTRIM5αによって感染が阻害されるプロリンを持つHIV-2に感染していると血中のウイルス量が低いことから、119番目のアミノ酸を含むカプシド領域がヒトTRIM5αの標的であること、及びヒトTRIM5αがHIV-2感染個体内のウイルス増殖の制御に寄与していることが強く示唆された。感染者個体内で上記のアミノ酸変化が起きたことを示す事例は見つからなかったため、感染しているHIV-2のアミノ酸配列を解析することにより、感染者の予後予測が可能になると考えられる。

Research Products

• [Journal Article] Comparison of anti-viral activity of rhesus monkey and cynomolgus monkey TRIM5alphas against human immunodeficiency virus true 2 infection (2008)
  • Author(s): Kono K.
  • Journal Title: Virology. 373 Pages: 447-56
  • Peer Reviewed
• [Journal Article] A rapid recombination assay of HIV-1 using murine CD52 as a novel biomarker (2008)
  • Author(s): Sakuragi J.
  • Journal Title: Microbes Infect. 10 Pages: 396-404
  • Peer Reviewed
• [Journal Article] TRIM5alpha-independent anti-human immunodeficiency virus type 1 activity mediated by cyclophilin A in Old World monkey cells (2008)
  • Author(s): Nakayama EE.
  • Journal Title: Virology 375 Pages: 514-20
  • Peer Reviewed
• [Journal Article] Silencing of tripartite motif protein(TRIM)5alpha mediated anti-HIV-1 activity by truncated mutant of TRIM5alnha (2008)
  • Author(s): Maegawa H
  • Journal Title: J Virol Methods. 151 Pages: 249-56
  • Peer Reviewed
• [Journal Article] Impact of Glycosylation on Antigenicity of Simian Immunodeficiency Virus SIV239 : Induction of Rapid V1/V2 Specific Non-neutralizing Antibody and Delayed Neutralizing Antibody Following Infection with an Attenuated Deglycosylated SIV239 Mutant (2008)
  • Author(s): Sugimoto C.
  • Journal Title: J Gen Virol. 89 Pages: 554-66
  • Peer Reviewed
• [Journal Article] Comparison between Sendai virus and Adenovirus vectors to transduce HIV-1 genes into human dendritic cells (2008)
  • Author(s): Hosoya N.
  • Journal Title: J Med Virol. 80 Pages: 373-82
  • Peer Reviewed
• [Journal Article] Effects of CCR2 and CCR5 polymorphisms on HIV-1 infection in Thai females (2008)
  • Author(s): Wichukchinda N.
  • Journal Title: J Acquir Immune Defic Syndr 47 Pages: 293-97
  • Peer Reviewed
• [Journal Article] Comparison between Sendai virus and Adenovirus vectors to transduce HIV-1 genes into human dendritic cells. (2008)
  • Author(s): Hosoya, N.
  • Journal Title: Journal of Medical Virology. (in press)
  • Peer Reviewed
• [Journal Article] Effects of CCR2 and CCR5 polymorphisms on HIV-1 infection in Thai females. (2008)
  • Author(s): Wichukchinda, N.
  • Journal Title: Journal of AIDS. (in press)
  • Peer Reviewed
• [Journal Article] Comparison of anti-viral activity of rhesus monkey and cynomolgus monkey TRIM5α s against HIV-2 infection. (2008)
  • Author(s): Kono, K.
  • Journal Title: Virology. (in press)
  • Peer Reviewed
• [Journal Article] A rapid recombination assayof HIV-1 using murine CD52 as a novel biomarker. (2008)
  • Author(s): Sakuragi, J.
  • Journal Title: Microbes and Infection (in press)
  • Peer Reviewed
• [Journal Article] A three-base-deletion polymorphism in the upstream non-coding region of human interleukin 7 (IL-7) gene could enhance levels of IL-7 expression. (2007)
  • Author(s): Song, H.
  • Journal Title: International Journal of Imuunogenetics. 34 Pages: 107-13
  • Peer Reviewed
• [Journal Article] The polymorphisms in DC-SIGNR affect the susceptibility to HIV-1 infection. (2007)
  • Author(s): Wichukchinad, N.
  • Journal Title: AIDS. Res. Hum. Retrovir. 23 Pages: 686-92
  • Peer Reviewed
• [Journal Article] ANTI-RETROVIRAL DRUG RESISTANCE-ASSOCIATED MUTATIONS AMONG NON-SUBTYPEB HIV-1-INFECTED KENYAN CHILDREN WITH TREATMENT FAILURE. (2007)
  • Author(s): Lwembe, R.
  • Journal Title: J. Med. Virol. 79 Pages: 865-72
  • Peer Reviewed
• [Journal Article] Retro-transduction by virus pseudotyped with glycoprotein of vesicular stomatitis virus. (2007)
  • Author(s): Ohishi, M.
  • Journal Title: Virology. 362 Pages: 131-8
  • Peer Reviewed
• [Journal Article] RANTES-28G delays and DC-SIGN-139C enhances AIDS progression in HIV-1-infected Japanese hemophiliacs. (2007)
  • Author(s): Koizumi, Y.
  • Journal Title: AIDS Research and Human Retroviruses. 23 Pages: 713-9
  • Peer Reviewed
• [Journal Article] Wild type and H43Y variant of human TRIM5alpha show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro. (2007)
  • Author(s): Nakayama, E.E.
  • Journal Title: Immunogenetics. 59 Pages: 511-5
  • Peer Reviewed
• [Journal Article] A single amino acid of the human immunodeficiency virus type 2 capsid affects its replication in the presence of cynomolgus monkey and human TRIM5alphas. (2007)
  • Author(s): Song, H.
  • Journal Title: J Virol. 81 Pages: 7280-5
  • Peer Reviewed
• [Journal Article] Minimal region sufficient for genome dimerization in the human immunod eficiency virus type 1 virion and its potential roles in the early stages of viral replication. (2007)
  • Author(s): Sakuragi, J.
  • Journal Title: J Virol. 81 Pages: 7985-92
  • Peer Reviewed
• [Journal Article] Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. (2007)
  • Author(s): Koh, Y.
  • Journal Title: J Biol Chem. 282 Pages: 28709-20
  • Peer Reviewed
• [Journal Article] Polymorphisms in CCR5 chemokine receptor gene in Japan. (2007)
  • Author(s): Liu, H.
  • Journal Title: Int J Immunogenet. 34 Pages: 325-335
  • Peer Reviewed
• [Journal Article] Host Genetic Analysis of HIV-1 Subtype CRF01-AE(E)-Infected Thai Patients with Different Rates of Disease Progression. (2007)
  • Author(s): Louisirirotchanakul, S.
  • Journal Title: AIDS Research and Human Retroviruses. 23 Pages: 1605-1607
  • Peer Reviewed
• [Journal Article] Impact of Glycosylation on Antigenicity of Simian Immunodeficiency Virus SIV239: Induction of Rapid V1/V2 Specific Non-neutralizing Antibody and Delayed Neutralizing Antibody Following Infection with an Attenuated Deglycosylated SIV239 Mutant. (2007)
  • Author(s): Sugimoto, C.
  • Journal Title: Journal of General Virology. 89 Pages: 554-66
  • Peer Reviewed
• [Presentation] カプシド変異とウイルス増殖 (2008)
  • Author(s): 中山英美
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-27
• [Presentation] HIV-2感染阻害におけるアカゲザル、カニクイザルTRIM5αの違い (2008)
  • Author(s): 河野健
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-27
• [Presentation] HIV-1ゲノム二量体化とウイルスゲノム組替えの厳密な相関 (2008)
  • Author(s): 櫻木淳一
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-27
• [Presentation] HIV-1 Gag前駆体プロセシングのゲノム二量体化への影響 (2008)
  • Author(s): 大石真久
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-27
• [Presentation] ドメイン欠失TRIM5alpha変異体によるTRIM5alphaのHIV-1抵抗性の解除 (2008)
  • Author(s): 前川彦一郎
  • Organizer: 第22回日本エイズ学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-26
• [Presentation] Gagと相互作用する細胞因子 (2008)
  • Author(s): 塩田達雄
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-27
• [Presentation] カプシド変異とウイルス増殖 (2008)
  • Author(s): 中山英美
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-27
• [Presentation] HIV-2感染阻害におけるアカゲザル、カニクイザルTRIM5αの違い (2008)
  • Author(s): 河野健
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-27
• [Presentation] レトロウイルスゲノム二量体化とウイルスゲノム組替えの厳密な相関 (2008)
  • Author(s): 櫻木淳一
  • Organizer: 第56回日本ヴイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] ドメイン欠失TRIM5α変異体によるTRIM5αのHIV-1抵抗性の解除 (2008)
  • Author(s): 前川彦一郎
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] A single amino acid of the human immunodeficiency virus type 2 capsid affects its replication in the presence of cynomolgus monkey and human TRIM5alphas. (2008)
  • Author(s): Song, H
  • Organizer: Conference for Retrovirus and Opportunistic Infection 2008
  • Place of Presentation: Boston, USA
  • Year and Date: 2008-02-04
• [Presentation] HIV-1ゲノム組換え標的の必要条件に関する解析 (2007)
  • Author(s): 櫻木 淳一
  • Organizer: 第21回日本エイズ学会学術集会
  • Place of Presentation: 広島
  • Year and Date: 2007-11-28
• [Presentation] サイクロフィリンAのHIV-1感染阻害効果 (2007)
  • Author(s): 中山 英美
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] HIV-1ゲノム組換え標的の必要条件 (2007)
  • Author(s): 櫻木 淳一
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] HIV-1のゲノム二量体化とウイルス粒子成熟との相関に関する研究 (2007)
  • Author(s): 大石真久
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22