Study of anti-APOBEC3G activities of HIV-1 Vif proteins among different subtypes

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TOKUNAGA Kenzo National Institute of Infectious Diseases, Dept of Pathology, PI (50342895)
• Co-Investigator(Kenkyū-buntansha): TATSUMI Masashi Natl Inst of Infectious Diseases, AIDS Res Ctr, Chief (00133629) ; ISHIZAKA Yukihito Internatl Med Ctr of Japan, Dept. of Intractable Diseases, Dept. Head (30281687) ; SATA Tetsutaro Natl Inst of Infectious Diseases, Dept of Pathology, Dept. Head (00162397)
• Project Period (FY): 2006 – 2007
• Keywords: HIV-1 / subtype / Vif / APOBEC3

Research Abstract

Antiretroviral cytidine deaminase APOBEC3G, which is abundantly expressed in peripheral blood lymphocytes and macrophages, strongly protects these cells against HIV-I infection. The Vif protein of HIV-1 overcomes this antiviral effect by inducing proteasome-mediated degradation of APOBEC3G, and is a key for maintaining viral infectivity. The vif gene, which is 579-bp long, displays high genetic diversity among HIV-I subtypes and it is therefore intriguing to address whether Vif proteins derived from different subtypes might be differ in the viral defense activity against APOBEC3G. To test this, we created expression plasmids encoding Vif proteins derived from subtypes A, B, C, CRF01_AE, and CRF02_AG clinical isolates and compared their anti-APOBEC3G activities. Viruses, produced from cells in the presence of APOBEC3G and Vif proteins of different subtypes, showed differential viral infectivities, that is, subtype C-derived Vif proteins showed exclusively high anti-APOBEC3G activities, compared with any. other subtype-derived Vif proteins, and this was found to be because of the different levels of proteasomal APOBEC3G degradation by Vif, depending on subtypes. To determine which portion of subtype C-Vif protein would be responsible for the robust anit-APOBEC3G activities, we created chimeric Vif constructs between subtypes B and C, and further pursued the responsible amino acid (s) by generating point mutants of Vif plasmids. As a result, we identified two amino acids at N-terminus responsible for subtype C-Vif-specific anti-APOBEC3G activity. Intriguingly, one of these amino acids is contained in the conserved sequence which is proposed to be involved in the interaction with APOBEC3G, suggesting that subtype C-vif might be able to bind APOBEC3G more efficiently than do Vif proteins of other subtypes. These results imply that biological differences of Vif proteins among subtypes might have an impact on viral transmissibility.

Research Products

• [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
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. (2008)
  • Author(s): Haga, S., Yamamoto, N., Nakai-Murakami, C., Osawa, Y., Tokunaga, K., Sata, T., Yamamoto, N., Sasazuki, T., and Ishizaka, Y.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 105 Pages: 7809-7814
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination. (2007)
  • Author(s): Nakai-Murakami, C., Shimura, M., Kinomoto, M., Takizawa, Y., Tokunaga, K., Taguchi, T., Hoshino, S., Miyagawa, K., Sata, T., Kurumizaka, H., Yuo, A., and Ishizaka, Y.
  • Journal Title: Oncogene 26 Pages: 477-486
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Successful Mouse Cloning of an Outbred Strain by Tricho statin A Treatment after Somatic Nuclear Transfer. (2007)
  • Author(s): Kishigami, S., Bui, H. T., Wakayama, S., Tokunaga, K., Thuan, N. V., Hikichi, T., Mizutani, E., Ohta, H., Suetsugu, R., Sata, T. and Wakayama, T.
  • Journal Title: J. Reprod. Dev. 53 Pages: 165-170
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition. (2007)
  • Author(s): Kinomoto, M, Kanno, T, Shimura, M, Ishizaka, Y, Kojima, A, Kurata, T, Sata, T, and Tokunaga K.
  • Journal Title: Nucleic Acids Res. 35 Pages: 2955-2964
  • Description: 「研究成果報告書概要(和文)」より
  • 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., Kitagawa, Y., Utachee, P., Jinnopat, P., Dhepakson, P., Isarangkura-Na-Ayuthaya, P., Tokunaga, K., Sato, H., Komano, J, Yamamoto, N, Oguchi, S., Natori, Y., Ikuta, K.
  • Journal Title: Biochem. Biophys. Res. Commun. 359 Pages: 729-734
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] HiV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination. (2007)
  • Author(s): Nakai-Murakami, C., Shimura, M., Kinomoto, M., Takizawa, Y., Tokunaga, K., Taguchi, T., Hoshino, S., Miyagawa, K., Sata, T., Kurumizaka, H., You, A., Ishizaka, Y.
  • Journal Title: Oncogene 26 Pages: 477-486
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Successful Mouse Cloning of an Outbred Strain by Trichostatin A Treatment after Somatic Nuclear Transfer. (2007)
  • Author(s): Kishigami, S., Bui, H. T., Wakayama, S., Tokunaga, K., Thuan, N.V., Hikichi, T., Mizutani, E., Ohta, H., Suetsugu, R., Sata, T. Wakayama, T.
  • Journal Title: J. Reprod. Dev 53 Pages: 165-170
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition. (2007)
  • Author(s): Kinomoto, M, Kanno, T, Shimura, M, Ishizaka, Y, Kojima, A, Kurata, T, Sata, T, Tokunaga K.
  • Journal Title: Nucleic Acids Res. 35 Pages: 2955-2964
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] HIV-1 Vpr induces DNA double-strand breaks. (2006)
  • Author(s): Tachiwana, H., Shimura, M., Nakai-Murakami, C., Tokunaga, K., Takizawa, Y., Sata, T., Kurumizaka, H., and Ishizaka, Y.
  • Journal Title: Cancer Res. 66 Pages: 627-631
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Tristetraprolin inhibits HIV-1 production by binding to genomic RNA. (2006)
  • Author(s): Maeda, M., Sawa, H., Tobiume, M., Tokunaga, K., Hasegawa, H., Ichinohe, T., Sata, T., Moriyama, M., Hall, W. W., Kurata, T., and Takahashi, H.
  • Journal Title: Microbes Infect. 8 Pages: 2647-2656
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] HIV-1 Vpr induces DNA double -strand breaks. (2006)
  • Author(s): Tachiwana, H., Shimura, M., Nakai-Murakami, C., Tokunaga, K., Takizawa, Y., Sata, T., Kurumizaka, H., Ishizaka, Y.
  • Journal Title: Cancer Res. 66 Pages: 627-631
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tristetraprolin inhibits HIV-1 production by binding to genomic RNA. (2006)
  • Author(s): Maeda, M., Sawa, H., Tobiume, M., Tokunaga, K., Hasegawa, H., Ichinohe, T., Sata, T., Moriyama, M., Hall, W. W., Kurata, T., Takahashi, H.
  • Journal Title: Microbes Infect 8 Pages: 2647-2656
  • Description: 「研究成果報告書概要(欧文)」より
• [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.
  • Author(s): Kitagawa, Y., Kameoka, M., Shoji-Kawata, S., Iwabu, Y., Mizuta, H., Tokunaga, K., Fujino, M., Natori, Y., Yura, Y. Ikuta, K.
  • Journal Title: Virology 373 Pages: 171-180
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry.
  • Author(s): Haga, S., Yamamoto, N., Nakai-Murakami, C., Osawa, Y., Tokunaga, K., Sata, T., Yamamoto, N., Sasazuki, T., Ishizaka, Y.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A 105 Pages: 7809-7814
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] HIV-1 Vprによる核膜異常. (2007)
  • Author(s): 志村まり、前島一博、宮澤雅之、森美樹、徳永研三、佐多徹太郎、今本尚子、瀧澤俊博、石坂幸人
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 20071200
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1アクセサリー遺伝子産物Vprはウイルスのセントロメア近傍への挿入効率を上昇させる. (2007)
  • Author(s): 中井智嘉子、峯本譲、孫賓蓮、徳永研三、佐多徹太郎、石坂幸人
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 20071200
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] VprによるゲノムDNA二重鎖切断はマクロファージへのHIV-1感染効率を上昇させる. (2007)
  • Author(s): 孫賓蓮、星野重樹、中井智嘉子、佐多徹太郎、徳永研三、石坂幸人
  • Organizer: 第21回日本エイズ学会総会
  • Place of Presentation: 広島
  • Year and Date: 20071100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vifのサブタイプ依存的抗APOBEC3G活性に関わる責任領域の決定. (2007)
  • Author(s): 徳永研三、岩部幸枝、木ノ本正信、巽正志、石坂幸人、倉田毅、佐多徹太郎
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20071000
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vpu蛋白に相互作用する宿主因子の検索.第55回日本ウイルス学会総会 (2007)
  • Author(s): 岩部幸枝、木ノ本正信、石坂幸人、藤本景子、藤田英明、田中嘉孝、佐多徹太郎、徳永研三
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20071000
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] VprによるゲノムDNA二重鎖切断はマクロファージへのHIV-1感染効率を上昇させる. (2007)
  • Author(s): 孫賓蓮、星野重樹、中井智嘉子、佐多徹太郎、徳永研三、石坂幸人
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20071000
  • Description: 「研究成果報告書概要(和文)」より
• [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総会
  • Place of Presentation: 札幌
  • Year and Date: 20071000
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vprによる姉妹染色分体の早期分離異常. (2006)
  • Author(s): 志村まり、豊田雄介、木ノ本正信、徳永研三、依田欣哉、柳田充弘、佐多徹太郎、石坂幸人
  • Organizer: 第29回日本分子生物学会
  • Place of Presentation: 名古屋
  • Year and Date: 20061200
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ヒトレトロトランスポゾンLINE-1に対するDNA編集酵素APOBEC3の抑制効果. (2006)
  • Author(s): 木ノ本正信、志村まり、石坂幸人、佐多徹太郎、徳永研三
  • Organizer: 第29回日本分子生物学会
  • Place of Presentation: 名古屋
  • Year and Date: 20061200
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Differential inhibitory activities of APOBEC3 family proteins on retroviruses and LINE-1 retrotransposon. (2006)
  • Author(s): Kinomoto M, Shimura M, Ishizaka Y, Sata T, and Tokunaga K
  • Organizer: 3rd Dominique Dormont International Conference on "Host pathogen interactions in chronic infections"
  • Place of Presentation: Bordeaux, France
  • Year and Date: 20061200
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 宿主因子APOBEC3Gに対するHIV-1 Vifの抑制活性の多様性. (2006)
  • Author(s): 徳永研三、木ノ本正信、坂本優子、巽正志、志村まり、石坂幸人、倉田毅、佐多徹太郎
  • Organizer: 第54回日本ウイルス学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20061100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] APOBEC3ファミリーによるLINE-1レトロトランスポゾン抑制効果. (2006)
  • Author(s): 徳永研三、木ノ本正信、志村まり、石坂幸人、佐多徹太郎
  • Organizer: 第54回日本ウイルス学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20061100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] マウス細胞を利用したHIV-1複製に関与する宿主因子の検索. (2006)
  • Author(s): 木ノ本正信、岸上哲士、佐多徹太郎、徳永研三
  • Organizer: 第54回日本ウイルス学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20061100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] G型肝炎ウイルス (GBV-C/HGV)産生系の樹立. (2006)
  • Author(s): 木ノ本正信、阿部賢治、鈴木哲朗、倉田 毅、佐多徹太郎、徳永研三
  • Organizer: 第54回日本ウイルス学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20061100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] KSHVとHIV-1の重感染における分子機構についての研究. (2006)
  • Author(s): 木ノ本正信、岸上哲士、佐多徹太郎、片野晴隆、徳永研三
  • Organizer: 第54回日本ウイルス学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20061100
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vpr Causes Aberrant Sister Chromatid Separation. (2006)
  • Author(s): Shimura, M., Toyoda, Y., Kinomoto, M., Tachiwana, H., Tokunaga, K., Kurumizaka, H., Yoda, K., Yanagida, M., Sata, T., and Ishizaka, Y.
  • Organizer: 第20回国際生化学・分子生物学会議
  • Place of Presentation: 京都
  • Year and Date: 20060600
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vpr induces DA double-strand breaks. (2006)
  • Author(s): Tachiwana, H., Nakai-Murakami, C., Hoshino, S., Shimura, M., Taguchi, T., Kurumizaka, H., Tokunaga, K., Sata, T., and Ishizaka, Y.
  • Organizer: Cold Spring Harbor Laboratory Meeting.
  • Place of Presentation: NY, USA.
  • Year and Date: 20060523-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] HIV-1 Vpr induces DA double-strand breaks. (2006)
  • Author(s): Tachiwana, H., Nakai-Murakami, C., Hoshino, S., Shimura, M., Taguchi, T., Kurumizaka, H., Tokunaga, K., Sata, T., Ishizaka, Y.
  • Organizer: Cold Spring Harbor Laboratory Meeting.
  • Place of Presentation: NY, USA
  • Year and Date: 20060523-28
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 3rd Dominique Dormont International Conference
  • Author(s): Kinomoto M, Shimura M, Ishizaka Y, Sata T, Tokunaga K Differential inhibitory activities of APOBEC3 family proteins on retroviruses, LINE-1 retrotransposon.
  • Description: 「研究成果報告書概要(欧文)」より