Regulation of APOBEC3 gene expression and its transcript splicing

• Project/Area Number: 21390143
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kinki University
• Principal Investigator: MIYAZAWA Masaaki 近畿大学, 医学部, 教授 (60167757)
• Co-Investigator(Kenkyū-buntansha): KAWAHARA Sachiyo 近畿大学, 医学部, 講師 (60297629) ; HAKATA Yoshiyuki 近畿大学, 医学部, 助教 (30344500) ; TAKAMURA Shiki 近畿大学, 医学部, 助教 (90528564)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 個体 / 感染抵抗性 / 宿主因子 / 遺伝子発現 / APOBEC3 / 遺伝子多型 / スプライシング / 翻訳効率 / 進化 / レトロウイルス / 複製制御 / シチジンデアミナーゼ / 発現制御 / エキソン / 単一塩基多型 / 中和抗体 / Bリンパ球 / 活性化

Research Abstract

Polymorphisms at the mouse APOBEC3(mA3) gene locus have been associated with different susceptibilities to infection with mouse leukemia viruses. In virus-resistant C57BL/6(B6) mice, mA3 transcripts and protein are more abundant than those in susceptible BALB/c mice, and these strains of mice also express mA3 transcripts with different splicing patterns. B6 mice express predominantly the exon 5-deficient transcript, which confer more efficient translation than the full-length transcript. By employing in vitro splicing assays using genomic DNA clones, we identified two critical determinants that regulate exon 5 inclusion into mA3 transcripts : the number of TCCT repeats upstream of exon 5 and the newly identified single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary.

Research Products

• [Journal Article] 生理的に機能するレトロウイルス複製制限因子APOBEC3の分子進化 (2012)
  • Author(s): 宮澤正顯
  • Journal Title: ウイルス Volume: 62(印刷中)
  • NAID: 10030767931
  • Peer Reviewed
• [Journal Article] Two genetic determinants acquired late in Mus evolution regulate the inclusion of exon 5, which alters mouse APOBEC3 translation efficiency (2012)
  • Author(s): Li, J., Y. Hakata, E. Takeda, Q. Liu, Y. Iwatani, C. A. Kozak, M. Miyazawa
  • Journal Title: PLoS Pathogens Volume: 8 Issue: 1 Pages: e1002478-e1002478
  • DOI: 10.1371/journal.ppat.1002478
  • NAID: 120006985441
  • Peer Reviewed
• [Journal Article] Immunological approaches for healthy longevity (2012)
  • Author(s): Miyazawa, M., 他
  • Journal Title: Anti-Aging Medicine Volume: 9 Pages: 43-50
• [Journal Article] An evolutionary analysis of RAC2 identifies haplotypes associated with human autoimmune diseases (2011)
  • Author(s): Sironi, M., F. R. Guerini, C. Agliardi, M. Biasin, R. Cagliani, M. Fumagalli, D. Caputo, A. Cassinotti, S. Ardizzone, M. Zanzottera, E. Bolognesi, S. Riva, Y. Kanari, M. Miyazawa, M. Clerici
  • Journal Title: Mol. Biol. Evol Volume: 28 Issue: 12 Pages: 3319-3329
  • DOI: 10.1093/molbev/msr164
  • Peer Reviewed
• [Journal Article] Natural killer cells recognize Friend retrovirusinfected erythroid progenitor cells through NKG2D-RAE-1 interactions in vivo (2011)
  • Author(s): Ogawa, T., S. Tsuji-Kawahara, T. Yuasa, S. Kinoshita, T. Chikaishi, S. Takamura, H. Matsumura, T. Seya, T. Saga, M. Miyazawa
  • Journal Title: J. Virol Volume: 85 Issue: 11 Pages: 5423-5435
  • DOI: 10.1128/jvi.02146-10
  • Peer Reviewed
• [Journal Article] Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice (2011)
  • Author(s): Hayasaka, N., K. Aoki, S. Kinoshita, S. Yamaguchi, J. K. Wakefield, S. Tsuji-Kawahara, K. Horikawa, H. Ikegami, S. Wakana, T. Murakami, R. Ramabhadran, M. Miyazawa, S. Shibata
  • Journal Title: PLoS ONE Volume: 6 Issue: 3 Pages: e17655-e17655
  • DOI: 10.1371/journal.pone.0017655
  • Peer Reviewed
• [Journal Article] A hole in the T-cell repertoire induced after retroviral infection of immunocompetent adult mice (2011)
  • Author(s): Miyazawa, M.
  • Journal Title: Retrovirology Volume: 8 Pages: 30-30
• [Journal Article] Immunopathogenesis in HIV-1 infection (2011)
  • Author(s): 田中勇悦, 他
  • Journal Title: The Journal of AIDS Research Volume: 13 Pages: 63-69
• [Journal Article] Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice. (2011)
  • Author(s): Hayasaka, N., 他
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Natural killer cells recognize Friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions in vivo. (2011)
  • Author(s): Ogawa, T., 他
  • Journal Title: Journal of Virology Volume: 86(印刷中)
  • Peer Reviewed
• [Journal Article] Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV (2010)
  • Author(s): Sugimoto C., S. Watanabe, T. Naruse, E. Kajiwara, T. Shiino, N. Umano, K. Ueda, H. Sato, S. Ohgimoto, V. Hirsch, F. Villinger, A. A. Ansari, A. Kimura, M. Miyazawa, Y. Suzuki, N. Yamamoto, Y. Nagai, K. Mori
  • Journal Title: PLoS One Volume: 5 Issue: 7 Pages: e11678-e11678
  • DOI: 10.1371/journal.pone.0011678
  • Peer Reviewed
• [Journal Article] Diversity of MHC class I genes in Burmese-origin rhesus macaques (2010)
  • Author(s): Naruse, T. K., Z. Chen, R. Yanagida, T. Yamashita, Y. Saito, K. Mori, H. Akari, Y. Yasutomi, M. Miyazawa, T. Matano, A. Kimura
  • Journal Title: Immunogenetics Volume: 62 Issue: 9 Pages: 601-611
  • DOI: 10.1007/s00251-010-0462-z
  • Peer Reviewed
• [Journal Article] Response to comment on "Premature terminal exhaustion of Friend virus-specific effector CD8^+T cells by rapid induction of multiple inhibitory receptors." (2010)
  • Author(s): Takamura, S., M. Miyazawa
  • Journal Title: J. Immunol Volume: 185 Pages: 1349-1350
  • Peer Reviewed
• [Journal Article] Persistence of viremia and production of neutralizing antibodies differentially regulated by polymorphic APOBEC3 and BAFF-R loci in Friend virus-infected mice (2010)
  • Author(s): Tsuji-Kawahara, S., T. Chikaishi, E. Takeda, M. Kato, S. Kinoshita, E. Kajiwara, S. Takamura, M. Miyazawa
  • Journal Title: J. Virol Volume: 84 Issue: 12 Pages: 6082-6095
  • DOI: 10.1128/jvi.02516-09
  • Peer Reviewed
• [Journal Article] Premature terminal exhaustion of Friend virus-specific effector CD8^+T cells by rapid induction of multiple inhibitory receptors (2010)
  • Author(s): Takamura, S., S. Tsuji-Kawahara, H. Yagita, H. Akiba, M. Sakamoto, T. Chikaishi, M. Kato, M. Miyazawa
  • Journal Title: J. Immunol Volume: 184 Issue: 9 Pages: 4696-4707
  • DOI: 10.4049/jimmunol.0903478
  • Peer Reviewed
• [Journal Article] Premature terminal exhaustion of Friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors. (2010)
  • Author(s): Takamura, S., 他
  • Journal Title: The Journal of Immunology Volume: 184 Pages: 4696-4707
  • Peer Reviewed
• [Journal Article] Persistence of viremia and production of neutralizing antibodies differentially regulated by polymorphic APOBEC3 and BAFF-R loci in Friend virus-infected mice. (2010)
  • Author(s): Tsuji-Kawahara, S., 他
  • Journal Title: Journal of Virology Volume: 84 Pages: 6082-6095
  • Peer Reviewed
• [Journal Article] Response to comment on "Premature terminal exhaustion of Friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors." (2010)
  • Author(s): Takamura, S., M.Miyazawa
  • Journal Title: The Journal of Immunology Volume: 185 Pages: 1349-1350
  • Peer Reviewed
• [Journal Article] Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV. (2010)
  • Author(s): Sugimoto C., 他
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] Premature terminal exhaustion of Friend virus-specific effector CD8^+ Tcells by rapid induction of multiple inhibitory receptors (2010)
  • Author(s): Takamura, S., 他
  • Journal Title: J.Immunol. 184(印刷中)
  • Peer Reviewed
• [Journal Article] Replies : The 'immunologic advantages' of HIV-exposed seronegative individuals (2009)
  • Author(s): Miyazawa, M., M. Clerici
  • Journal Title: AIDS Volume: 23 Issue: 12 Pages: 1612-1612
  • DOI: 10.1097/qad.0b013e32832d74ca
  • Peer Reviewed
• [Journal Article] The "immunologic advantage" of HIV-exposed seronegative individuals (2009)
  • Author(s): Miyazawa M., L. Lopalco, F. Mazzotta, S. Lo Caputo, F. Veas, M. Clerici
  • Journal Title: AIDS Volume: 23 Issue: 2 Pages: 161-175
  • DOI: 10.1097/qad.0b013e3283196a80
  • Peer Reviewed
• [Journal Article] The 'immunologic advantages' of HIV-exposed seronegative individuals : authors' reply. (2009)
  • Author(s): 宮澤正顯, 他
  • Journal Title: AIDS 23 Pages: 1612-1612
  • Peer Reviewed
• [Journal Article] JCO事故における造血幹細胞移植をめぐって (2009)
  • Author(s): 宮澤正顯
  • Journal Title: 環境と健康 22 Pages: 335-351
  • Peer Reviewed
• [Journal Article] Development of a new disinfectant with very strong anti-influenza viralactivity : a preliminary report (2009)
  • Author(s): Takakmwa, H., 他
  • Journal Title: Environ.Health Prev.Med. 15 Pages: 121-123
  • Peer Reviewed
• [Journal Article] Mouse APOBEC3 affects the production of virus-neutralizing antibodies by restricting early retroviral replication, not by altering the B-cell repertoire (2009)
  • Author(s): 宮澤正顯, 他
  • Journal Title: Retrovirology 6
• [Presentation] Resistance to HIV infection and AIDS progression (2012)
  • Author(s): Miyazawa, M
  • Organizer: NEKKEN Research Conference : HIV Patients Care and Research in Southeast Asia
  • Place of Presentation: Nagasaki, Japan
• [Presentation] Resistance to HIV infection and AIDS progression (2012)
  • Author(s): Masaaki Miyazawa
  • Organizer: NEKKEN Research Conference : HIV Patients Care and Research in Southeast Asia
  • Place of Presentation: 長崎大学ポンペ会館(長崎市)
• [Presentation] Production of virus-neutralizing antibodies and protection against lethal retroviral infection in AID-deficient mice (2011)
  • Author(s): Kato, M., et al.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Infection of thymus with murine retrovirus induces virus-specific central tolerance that prevents dynamic differentiation of functional memory CD8^+T cells (2011)
  • Author(s): Takamura, S., et al.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Functional consequences of mouse APOBEC3 gene polymorphisms and multiple genetic factors that influence the production of virus-neutralizing antibodies in Friend virus-infected mice (2011)
  • Author(s): Miyazawa, M., et al.
  • Organizer: The 23rd Workshop on Retrovirla Pathogenesis
  • Place of Presentation: Montpellier, Farance
• [Presentation] Host immune responses determine integration of either F-MuLV alone or F-MuLV plus SFFV in Friend virus leukemogenesis (2011)
  • Author(s): Miyazawa, M., et al.
  • Organizer: The 23rd Workshop on Retrovirla Pathogenesis
  • Place of Presentation: Montpellier, Farance
• [Presentation] A hole in the T-cell repertoire induced after retroviral infection of immunocompetent adult mice (2011)
  • Author(s): Miyazawa, M., et al.
  • Organizer: Frontiers of Retrovirology 2011
  • Place of Presentation: Amsterdam, The Netherlands
• [Presentation] A hole in the T-cell repertoire induced after retroviral infection of immunocompetent adult mice (2011)
  • Author(s): Miyazawa, M., 他
  • Organizer: Frontiers of Retrovirology 2011
  • Place of Presentation: Moevenpick Hotel, Amsterdam, The Netherlands
• [Presentation] Host immune responses determine integration of either F-MuLV alone or F-MuLV plus SFFV in Friend virus leukemogenesis (2011)
  • Author(s): Miyazawa, M., 他
  • Organizer: The 23rd Workshop on Retroviral Pathogenesis
  • Place of Presentation: Le Corum, Montpellier, Farance
• [Presentation] Functional consequences of mouse APOBEC3 gene polymorphisms and multiple genetic factors that influence the production of virus-neutralizing antibodies in Friend virus-infected mice (2011)
  • Author(s): Miyazawa, M., 他
  • Organizer: The 23rd Workshop on Retroviral Pathogenesis
  • Place of Presentation: Le Corum, Montpellier, Farance
• [Presentation] Production of virus-neutralizing antibodies and protection against lethal retroviral infection in AID-deficient mice (2011)
  • Author(s): Kato, M., 他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
• [Presentation] Infection of thymus with murine retrovirus induces virus-specific central tolerance that prevents dynamic differentiation of functional memory CD8+ T cells (2011)
  • Author(s): Takamura, S., 他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
• [Presentation] HIV感染移行性の分子機構: Rac2とAPOBEC3 (2010)
  • Author(s): 宮澤正顯, 他
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-26
• [Presentation] 性麟症の最近の動向:HIVと性器クラミジアを中心に(教育講演) (2010)
  • Author(s): 宮澤正顯
  • Organizer: 第19回日本口腔感染症学会総会・学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-11-06
• [Presentation] High-level Rac2 expression associated with novel intron polymorphisms restricts HIV-1 replication in exposed seronegative individuals (2010)
  • Author(s): Kanari, Y., et al.
  • Organizer: NEKKEN Research Conference "Ten years achievements of the Lampang HIV cohort in Northen Thailand."
  • Place of Presentation: Nagasaki, Japan
  • Year and Date: 2010-10-27
• [Presentation] High-level Rac2 expression associated with novel intron polymorphisms restricts HIV-1 replication in exposed seronegative individuals. (2010)
  • Author(s): Kanari, Y., 他
  • Organizer: NEKKEN Research Conference "Ten years" achievements of the Lampang HIV cohort in Northen Thailand."
  • Place of Presentation: 長崎
  • Year and Date: 2010-10-27
• [Presentation] レトロウイルス遺伝子発現と糸球本病:拡大するヒトレトロウイルスの世界(特別講演) (2010)
  • Author(s): 宮澤正顯
  • Organizer: 第45回日本小児腎臓病学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-07-02
• [Presentation] HIV感染抵抗性の分子機構: Rac2とAPOBEC3(シンポジウム) (2010)
  • Author(s): 宮澤正顯, 他
  • Organizer: 第24回日本エイズ学会学術集会・総会
  • Place of Presentation: 東京
• [Presentation] レトロウイルス遺伝子発現と糸球体病変:拡大するヒトレトロウイルスの世界 (2010)
  • Author(s): 宮澤正顯
  • Organizer: 第45回日本小児腎臓病学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Genetic factors that confer resistance to HIV-1 acquisition in HIV-1-exposed but seronegative individuals in Italy and Thailand (2009)
  • Author(s): Miyazawa, M., et al.
  • Organizer: 4th Nagasaki Symposium on Tropical and Emerging Infectious Diseases
  • Place of Presentation: Nagasaki
• [Presentation] Mouse APOBEC3 affects the production of virus-neutralizing antibodies by restricting early retroviral replication, not by altering the B-cell repertoire (2009)
  • Author(s): Miyazawa, M., et al.
  • Organizer: Frontiers of Retrovirology 2011
  • Place of Presentation: Montpellier, France
• [Presentation] Mechanisms of immune evasion by Friend virus : T-cell exhaustion, B-cell hyperactivation, and their genetic control (2009)
  • Author(s): Miyazawa, M., et al.
  • Organizer: 21st International Workshop on Retroviral Pathogenesis
  • Place of Presentation: Castelnuovo Garfagnana, Lucca, Italy
• [Presentation] New metabolic markers derived from gamma and deltaretrovirus envelope glycoproteins (2009)
  • Author(s): Sitbon, M., et al.
  • Organizer: 21st International Workshop on Retroviral Pathogenesis
  • Place of Presentation: Castelnuovo Garfagnana, Lucca, Italy
• [Presentation] Mechanisms of immune evasion by Friend virus : T-cell exhaustion, B-cell hyperactivation, and their genetic control (2009)
  • Author(s): Miyazawa, M., 他
  • Organizer: 21st International Workshop on Retroviral Pathogenesis
  • Place of Presentation: Lucca, Italy
• [Presentation] New metabolic markers derived from gamma and deltaretrovirus envelope glycoproteins (2009)
  • Author(s): Sitbon, M., 他
  • Organizer: 21st International Workshop on Retroviral Pathogenesis
  • Place of Presentation: Lucca, Italy
• [Presentation] Mouse APOBEC3 affects the production of virus-neutralizing antibodies by restricting early retroviral replication, not by altering the B-cell repertoire (2009)
  • Author(s): Miyazawa, M., 他
  • Organizer: Frontiers of Retrovirology
  • Place of Presentation: Montpellier, France
• [Book] 解明病理学:病気のメカニズムを解く (2009)
  • Author(s): 宮澤正顯, 青笹克之
  • Publisher: 医歯薬出版
• [Book] 解明病理学:病気のメカニズムを解く (2009)
  • Author(s): 宮澤正顯
  • Total Pages: 827
  • Publisher: 医歯薬出版(株)
• [Remarks]
  • URL: http://www.med.kindai.ac.jp/immuno/konnano.htm
• [Remarks]
  • URL: http://www.med.kindai.ac.jp/immuno/konnano.htm
• [Remarks]
  • URL: http://www.med.kindai.ac.jp/immuno/konnano.htm