Molecular basis underlying different antiviral functions in the APOBEC3 family

• Project/Area Number: 15H04740
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Iwatani Yasumasa 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 部長 (90303403)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: レトロウイルス / 宿主因子 / APOBEC3 / 感染制御 / 核酸結合 / 構造解析 / 生化学 / HIV / ウィルス / 蛋白質 / 感染症 / 酵素 / 生体分子

Outline of Final Research Achievements

Cellular enzymes of the APOBEC3 family (7 members encoded in human) exhibit potent antiviral activity against retroviruses including HIV. However, HIV expresses viral factor, Vif protein, in its infected cells and abrogates the APOBEC3-mediated defense system. Structural determinations of APOBEC3 family proteins are required to understand their antiviral functions and Vif-mediated antagonisms. In this study, we determined high-resolution crystal structures of APOBEC3 family proteins (2 of them) and clarified their structural/biochemical features underlying their molecular mechanisms. Especially, our determination of APOBEC3H crystal structure and unexpected findings of its biochemical properties provide important insights into the APOBEC3-mediated antiviral mechanisms as well as cancer and genetic mutations.

Research Products

• [Journal Article] Distribution of Human Papillomavirus Genotype in Anal Condyloma Acuminatum Among Japanese Men: The Higher Prevalence of High Risk Human Papillomavirus in Men Who Have Sex with Men with HIV Infection (2018)
  • Author(s): Furukawa Satomi、Uota Shin、Yamana Tetsuo、Sahara Rikisaburo、Iihara Kuniko、Yokomaku Yoshiyuki、Iwatani Yasumasa、Sugiura Wataru
  • Journal Title: AIDS Research and Human Retroviruses Volume: 34 Issue: 4 Pages: 375-381
  • DOI: 10.1089/aid.2017.0197
  • Peer Reviewed
• [Journal Article] Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia (2018)
  • Author(s): Nemoto Michiko、Hattori Hiroyoshi、Maeda Naoko、Akita Nobuhiro、Muramatsu Hideki、Moritani Suzuko、Kawasaki Tomonori、Maejima Masami、Ode Hirotaka、Hachiya Atsuko、Sugiura Wataru、Yokomaku Yoshiyuki、Horibe Keizo、Iwatani Yasumasa
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 6956-6956
  • DOI: 10.1038/s41598-018-25260-8
  • Peer Reviewed / Open Access
• [Journal Article] Mapping Region of Human Restriction Factor APOBEC3H Critical for Interaction with HIV-1 Vif (2017)
  • Author(s): Nakashima Masaaki、Tsuzuki Shinya、Awazu Hiroaki、Hamano Akiko、Okada Ayaka、Ode Hirotaka、Maejima Masami、Hachiya Atsuko、Yokomaku Yoshiyuki、Watanabe Nobuhisa、Akari Hirofumi、Iwatani Yasumasa
  • Journal Title: Journal of Molecular Biology Volume: 429 Issue: 8 Pages: 1262-1276
  • DOI: 10.1016/j.jmb.2017.03.019
  • Peer Reviewed
• [Journal Article] Fusobacterium nucleatum detected simultaneously in a pyogenic liver abscess and advanced sigmoid colon cancer. (2017)
  • Author(s): Shigefuku R, Watanabe T, Kanno Y, Ikeda H, Nakano H, Hattori N, Matsunaga K, Matsumoto N, Kanno SI, Nosho K, Hachiya A, Iwatani Y, Matsumori T, Tsukikawa S, Makizumi R, Otsubo T, Yamamoto H, Itoh F.
  • Journal Title: Anaerobe Volume: 48 Pages: 144-146
  • DOI: 10.1016/j.anaerobe.2017.08.010
  • Peer Reviewed
• [Journal Article] Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region (2017)
  • Author(s): Nomaguchi Masako、Doi Naoya、Yoshida Tomoya、Koma Takaaki、Adachi Shun、Ode Hirotaka、Iwatani Yasumasa、Yokoyama Masaru、Sato Hironori、Adachi Akio
  • Journal Title: Frontiers in Microbiology Volume: 8 Pages: 2542-2542
  • DOI: 10.3389/fmicb.2017.02542
  • NAID: 120006937675
  • Peer Reviewed / Open Access
• [Journal Article] Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors (2017)
  • Author(s): Hachiya Atsuko、Kirby Karen A.、Ido Yoko、Shigemi Urara、Matsuda Masakazu、Okazaki Reiko、Imamura Junji、Sarafianos Stefan G.、Yokomaku Yoshiyuki、Iwatani Yasumasa
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 61 Issue: 8
  • DOI: 10.1128/aac.00315-17
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distribution of norovirus genotypes and subtypes in river water by ultra-deep sequencing-based analysis (2017)
  • Author(s): Boonchan M.、Motomura K.、Inoue K.、Ode H.、Chu P.Y.、Lin M.、Iwatani Y.、Ruchusatsawat K.、Guntapong R.、Tacharoenmuang R.、Chantaroj S.、Tatsumi M.、Takeda N.、Sangkitporn S.
  • Journal Title: Letters in Applied Microbiology Volume: 65 Issue: 1 Pages: 98-104
  • DOI: 10.1111/lam.12750
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular epidemiology of co-infection with hepatitis B virus and human immunodeficiency virus (HIV) among adult patients in Harare, Zimbabwe (2017)
  • Author(s): Baudi I, Iijima S, Chin'ombe N, Mtapuri-Zinyowera S, Murakami S, Isogawa M, Hachiya A, Iwatani Y, and Tanaka Y
  • Journal Title: Journal of Medical Virology Volume: 89 Issue: 2 Pages: 257-266
  • DOI: 10.1002/jmv.24641
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Structural basis of APOBEC3-Vif Interaction in the host-virus arms race (2016)
  • Author(s): 都築伸弥、岩谷靖雅
  • Journal Title: 生化学 Volume: 88 Issue: 5 Pages: 563-568
  • DOI: 10.14952/SEIKAGAKU.2016.880563
  • ISSN: 0037-1017
  • Year and Date: 2016-10-25
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels (2016)
  • Author(s): Nomaguchi M, Doi N, Sakai Y, Ode H, Iwatani Y, Ueno T, Matsumoto Y, Miyazaki Y, Masuda T, and Adachi A
  • Journal Title: Journal of Virology Volume: 90 Issue: 9 Pages: 4563-4578
  • DOI: 10.1128/jvi.02939-15
  • Peer Reviewed
• [Journal Article] APOBEC3G-mediated G-to-A hypermutation of the HIV-1 genome: the missing link in antiviral molecular mechanisms (2016)
  • Author(s): Okada A, and Iwatani Y
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 2027-2027
  • DOI: 10.3389/fmicb.2016.02027
  • Peer Reviewed / Open Access
• [Journal Article] Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study. (2016)
  • Author(s): Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, Sierra Madero J, Belloso W, Tu E, Silk D, Kelleher A, Harrigan R, Clark A, Sugiura W, Wolff M, Gill J, Gatell J, Fisher M, Clarke A, Ruxrungtham K, Prazuck T, Kaiser R, Woolley I, Arnaiz JA, Cooper D, Rockstroh JK, Mallon P, Emery S, and
  • Journal Title: Clinical infectious diseases Volume: 63 Issue: 1 Pages: 122-132
  • DOI: 10.1093/cid/ciw207
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Virological characteristics of hepatitis B genotype G/A2 recombination virus in Japan. (2016)
  • Author(s): Tsuzuki Y, Watanabe T, Iio E, Fujisaki S, Ibe S, Kani S, Hamada-Tsutsumi S, Yokomaku Y, Iwatani Y, Sugiura W, Okuse C, Okumura A, Sato Y, Tanaka Y.
  • Journal Title: Hepatol Res. Volume: 印刷中 Issue: 8 Pages: 75-783
  • DOI: 10.1111/hepr.12612
  • Peer Reviewed
• [Journal Article] HIV-1 CRF01_AE and subtype B transmission networks cross over: a new AE/B recombinant identified in Japan (2016)
  • Author(s): Hosaka M, Fujisaki S, Masakane A, Hattori J, Shiino T, Gatanaga H, Shigemi S, Okazaki R, Hachiya A, Matsuda M, Ibe S, Iwatani Y, Yokomaku Y, Sugiura W
  • Journal Title: AIDS Research and Human Retroviruses Volume: 32 Issue: 5 Pages: 412-419
  • DOI: 10.1089/aid.2015.0192
  • Peer Reviewed
• [Journal Article] Molecular Epidemiology of Enteric Viruses in Patients with Acute Gastroenteritis in Aichi Prefecture, Japan, 2008/09–2013/14 (2016)
  • Author(s): Nakamura N, Kobayashi S, Minagawa H, Matsushita T, Sugiura W, Iwatani Y
  • Journal Title: Journal of Medical Virology Volume: 88 Issue: 7 Pages: 1180-1186
  • DOI: 10.1002/jmv.24445
  • Peer Reviewed
• [Journal Article] Structural Insights into HIV-1 Vif-APOBEC3F Interaction (2016)
  • Author(s): Nakashima M, Ode H, Kawamura T, Kitamura S, Naganawa Y, Awazu H, Tsuzuki S, Matsuoka K, Nemoto M, Hachiya A, Sugiura W, Yokomaku Y, Watanabe N, Iwatani Y
  • Journal Title: Journal of Virology Volume: 90 Issue: 2 Pages: 1034-1047
  • DOI: 10.1128/jvi.02369-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Novel Drug-Resistant HIV-1 Circulating Recombinant Form CRF76_01B Identified by Near Full-Length Genome Analysis (2016)
  • Author(s): Ogawa S, Hachiya A, Hosaka1 M, Matsuda1 M, Ode1 H, Shigemi U, Okazaki R, Sadamasu K, Nagashima M, Toyokawa T, Tateyama M, Tanaka Y, Sugiura W, Yokomaku Y, Iwatani Y
  • Journal Title: AIDS Research and Human Retroviruses Volume: 32 Issue: 3 Pages: 284-289
  • DOI: 10.1089/aid.2015.0304
  • Peer Reviewed
• [Journal Article] Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance (2016)
  • Author(s): Nakashima M, Ode H, Suzuki K, Fujino M, Maejima M, Kimura Y, Masaoka T, Hattori J, Matsuda M, Hachiya A, Yokomaku Y, Suzuki A, Watanabe N, Sugiura W, Iwatani Y
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 61-61
  • DOI: 10.3389/fmicb.2016.00061
  • Peer Reviewed / Open Access
• [Journal Article] HIV-1感染急性期におけるサイトカインのプロファイル解析 (2016)
  • Author(s): 重見麗、蜂谷敦子、松田昌和、岡﨑玲子、小川慎太郎、伊藤恭子、健山正男、今村顕史、栁澤邦雄、矢野邦夫、藤井輝久、上田敦久、今村淳治、渡邊綱正、田中靖人、横幕能行、杉浦亙、岩谷靖雅
  • Journal Title: 日本エイズ学会誌 Volume: 18
  • NAID: 40020856373
  • Peer Reviewed
• [Journal Article] APOBEC3H polymorphisms associated with susceptibility to HIV-1 infection and AIDS progression in Japanese. (2015)
  • Author(s): Sakurai D, Iwatani Y, Ohtani H, Naruse TK, Terunuma H, Sugiura W, Kimura A.
  • Journal Title: Immunogenetics Volume: 67 Issue: 4 Pages: 253-257
  • DOI: 10.1007/s00251-015-0829-2
  • Peer Reviewed
• [Journal Article] Mutational analysis of HIV-2 Vpx shows that residue 109 in the poly-proline motif regulates degradation of SAMHD1 (2015)
  • Author(s): Halil Ibrahim Ciftci, Haruna Fujino, Ryoko Koga, Minami Yamamoto, Sogo Kawamura, Hiroshi Tateishi, Yasumasa Iwatani, Masami Otsuka, Mikako Fujita
  • Journal Title: FEBS Letters Volume: 未定 Issue: 13 Pages: 1505-1514
  • DOI: 10.1016/j.febslet.2015.04.038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance (2015)
  • Author(s): Hachiya A, Ode H, Matsuda M, Kito Y, Shigemi U, Matsuoka K, Imamura J, Yokomaku Y, Iwatani Y, Sugiura W
  • Journal Title: Antiviral Research Volume: 119 Pages: 84-88
  • DOI: 10.1016/j.antiviral.2015.04.014
  • Peer Reviewed
• [Journal Article] A cell-free enzymatic activity assay for the evaluation of HIV-1 drug resistance to protease inhibitors (2015)
  • Author(s): Matsunaga S, Masaoka T, Sawasaki T, Morishita R, Iwatani Y, Tatsumi M, Yamamoto N, Endo Y, Sugiura W, Ryo A
  • Journal Title: Frontiers in Microbiology Volume: 6 Pages: 1220-1220
  • DOI: 10.3389/fmicb.2015.01220
  • Peer Reviewed / Open Access
• [Journal Article] Quasispecies Analyses of the HIV-1 Near-full-length Genome with Illumina MiSeq (2015)
  • Author(s): Ode H, Matsuda M, Matsuoka K, Hachiya A, Hattori J, Kito Y, Yokomaku Y, Iwatani Y, Sugiura W
  • Journal Title: Frontiers in Microbiology Volume: 6 Pages: 1258-1258
  • DOI: 10.3389/fmicb.2015.01258
  • Peer Reviewed / Open Access
• [Presentation] Analysis of structural and functional roles of the HIV-1 Vif PPLP motif region (2017)
  • Author(s): 岩谷靖雅, 都築伸弥, 伊藤公平, 濱野章子, 久保田舞, 大出裕高, 松岡達也, 横幕能行, 渡邉信久, 蜂谷敦子
  • Organizer: 第65回 日本ウイルス学会学術集会
• [Presentation] HIV-1 VifPPLP領域のAPOBEC3の分解における役割 (2016)
  • Author(s): 都築伸弥, 大出裕高, 濵野章子, 岡田彩加, 粟津宏昭, 蜂谷敦子, 横幕能行, 岩谷靖雅
  • Organizer: 第30回日本エイズ学会
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-11-23
• [Presentation] APOBEC3HのHIV-1 Vif結合領域の構造学的研究 (2016)
  • Author(s): 粟津宏昭, 中島雅晶, 大出裕高, 濵野章子, 都築伸弥, 前島雅美, 岡田彩加, 蜂谷敦子, 横幕能行, 岩谷靖雅
  • Organizer: 第30回日本エイズ学会
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-11-23
• [Presentation] Structural Characterization of the APOBEC3H region important for HIV-1 Vif interaction (2016)
  • Author(s): Iwatani Y, Nakashima M, Tsuzuki S, Awazu H, Ode H, Maejima M, Okada A, Hamano A, Hachiya A, Yokomaku Y
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] COMPARATIVE ANALYSES OF HIV-1 AND HIV-2 INTEGRATION SITES (2016)
  • Author(s): 大出裕高，井上歩美，松田昌和，今村淳治，蜂谷敦子，横幕能行，岩谷靖雅
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] A study on false-positive serological cases for HIV-2 in Japan (2016)
  • Author(s): 前島雅美, 伊部史朗, 根本理子, 今橋真弓, 今村淳治, 蜂谷敦子, 松田昌和, 重見麗, 岡崎玲子, 杉浦亙, 横幕能行, 岩谷靖雅
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] Novel Mutation Patterns in HIV-1 Integrase Conferring High-Level Resistance to the First-generation Integrase Strand Transfer Inhibitors (2016)
  • Author(s): Hachiya A, Nakashima M, Sakurai Y, Shigemi U, Matsuda M, Okazaki R, Imamura J, Yokomaku Y, Iwatani Y
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] Structural features of the APOBEC3H region critical for HIV-1 Vif interaction (2016)
  • Author(s): Nakashima M, Tsuzuki S, Awazu H, Ode H, Maejima M, Hachiya A, Yokomaku Y, Watanabe N, Akari H, Iwatani Y
  • Organizer: Cold Spring Harbor Laboratory -Annual Retrovirus- Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] COMPARATIVE ANALYSES OF INTEGRATION SITES BETWEEN HIV-1 AND HIV-2 (2016)
  • Author(s): Ode H, Inoue A, Matsuda M, Imamura J, Hachiya A, Yokomaku Y, Iwatani Y
  • Organizer: Cold Spring Harbor Laboratory -Annual Retrovirus- Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] STRUCTURAL FEATURES OF THE APOBEC3H REGION CRITICAL FOR HIV-1 VIF INTERACTION (2016)
  • Author(s): Nakashima M, Tsuzuki S, Awazu H, Ode H, Maejima M, Hachiya A, Yokomaku Y, Watanabe N, Akari H, Iwatani Y
  • Organizer: Cold Spring Harbor Laboratory -Annual Retrovirus- Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] Nationwide Surveillance of Drug-resistant HIV-1 in Newly Diagnosed Patients in Japan. (2016)
  • Author(s): Yasumasa Iwatani
  • Organizer: 18th International Conference on Emerging Infectious Diseases (EID), AIDS panel
  • Place of Presentation: North Bethesda, MD, USA
  • Year and Date: 2016-01-11
  • Int'l Joint Research / Invited
• [Presentation] 細胞防御酵素を活用した抗HIV薬開発にむけて (2015)
  • Author(s): 岩谷靖雅
  • Organizer: 第6回 横幹連合コンファレンス
  • Place of Presentation: 名古屋
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] HIV-1が細胞因子APOBEC3による防御機構から逃れる分子機序 (2015)
  • Author(s): 岩谷靖雅
  • Organizer: 第56回 日本熱帯医学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] HIV-1 Vif によるAPOBEC3 分解機序から考察されるウイルスの巧み適応戦略 (2015)
  • Author(s): 岩谷靖雅
  • Organizer: 第29回 日本エイズ学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-30
  • Invited
• [Presentation] Structural insights into HIV-1 Vif interactions with APOBEC3 cytidine deaminases (2015)
  • Author(s): Yasumasa Iwatani
  • Organizer: 第63回 日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-21
  • Invited
• [Presentation] Comparative analysis of the antiviral APOBEC3C enzymes in primates: implication for degeneration of their catalytic activities (2015)
  • Author(s): Masaaki Nakashima, Hirotaka Ode, Shinya Tsuzuki, Hiroaki Awazu, Kenta Matsuda, Kei Sato, Atsuko Hachiya, Yoshiyukii Yokomaku, Nobuhisa Watanabe, Yasumasa Iwatani
  • Organizer: 第63回 日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-21
• [Presentation] HIV-1 Vif によるAPOBEC3分解の分子基盤 (2015)
  • Author(s): 岩谷靖雅
  • Organizer: 第17回 白馬シンポジウム in 米子
  • Place of Presentation: 米子
  • Year and Date: 2015-06-19
  • Invited
• [Presentation] STRUCTURE-BASED ANALYSIS OF HIV-1 VIF-APOBEC3F INTERACTION (2015)
  • Author(s): Nakashima, M., Ode, H., Kitamura, S., Mano, Y., Awazu, H., Hachiya, A., Yokomaku, Y., Watanabe, N., Sugiura, W., Iwatani, Y
  • Organizer: Cold Spring Harbor Laboratory -Annual Retrovirus- Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] QUASISPECIES EVALUATION ACROSS HIV-1 NEAR-FULL-LENGTH GENOME VIA ILLUMINA MISEQ (2015)
  • Author(s): Ode, H., Matsuda, M., Matsuoka, K., Hachiya, A., Yokomaku, Y., Iwatani, Y. Sugiura, W.
  • Organizer: Cold Spring Harbor Laboratory -Annual Retrovirus- Meeting
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, USA
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Remarks] 名古屋大学大学院医学研究科 免疫不全統御学講座
  • URL: https://www.med.nagoya-u.ac.jp/medical_J/laboratory/basic-med/aids-research/aids/
• [Remarks] 名古屋医療センター 臨床研究センター 感染・免疫研究部
  • URL: https://www.nnh.go.jp/crc/departments/infectious_diseases/