Clarify the role of autophagy in influenza A virus infection andreplication

• Project/Area Number: 22590274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagasaki University
• Principal Investigator: KITAZATO Kaio 長崎大学, 医歯薬学総合研究科, 准教授 (50372769)
• Co-Investigator(Renkei-kenkyūsha): KOMATSU Masaaki 東京都医学研究機構, 東京都臨床医学総合研究所, 副参事研究員 (90356254)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞医化学 / ウイルス複製 / オートファジー / 宿主標的 / インフルエンザウイルス / ウイルスＲＮＡ合成 / ウイルスタンパク質翻訳 / Hsp90 / mTORシグナル / 中国 / 国際情報交換 / PGG / 微小管結合タンパク質MIP-T3

Research Abstract

In this study, we established a cell line that constitutively expresses GFP-LC3, the molecular marker of autophagy, which can visualize the dynamics of autophagosome formation during influenza virus infection. We found that viral protein expression reduced in autophagy-deficient MEFs (MEFsAtg7-/-) which is relevant to the reduction in viral RNA synthesis including mRNA and genomic RNA. However, viral replication did not significantly affected by autophagy deficiency. Furthermore, viral entry into cell did not affected by autophagy deficiency, but Hsp 90 induction in response to viral infection and mTOR signalling were altered in MEFsAtg7-/-, suggesting that these autophagy-deficiency-induced host aberrant response might be responsive to the reduction of viral RNA synthesis.

Research Products

• [Journal Article] Cofilin , Wang Y., 1-mediated biphasic F-actin dynamics of neuronal cells affect herpes simplex virus 1 infection and replication. (2012)
  • Author(s): Xiang Y, Zheng K, Ju H, Wang S, Pei Y, Ding W, Chen Z, Wang Q, Qiu X, Zhong M, Zeng F, Ren Z, Qian C, Liu G, Kitazato K , Wang Y.
  • Journal Title: J Virol. Volume: 6(16) Pages: 8440-51
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ, et al
  • Journal Title: Autophagy Volume: 8(4) Pages: 445-544
  • Peer Reviewed
• [Journal Article] Guideline for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ,et al
  • Journal Title: Autophagy Volume: 8 Issue: 4 Pages: 445-544
  • DOI: 10.4161/auto.19496
  • Peer Reviewed
• [Journal Article] Cofilin 1-mediated biphasic F-actin dynamics of neuronal cells affect herpes simplex virus 1 infection and replication (2012)
  • Author(s): Xiang Y., et al
  • Journal Title: Journal of Virology Volume: 86 Issue: 16 Pages: 8440-8451
  • DOI: 10.1128/jvi.00609-12
  • Peer Reviewed
• [Journal Article] Pentagalloylglucose downregulates cofilin1 and inhibits HSV-1 infection (2011)
  • Author(s): Pei Y, Xiang YF, Chen JN, Lu CH, Hao J, Du Q, Lai CC, Qu C, Li S, Ju HQ, Ren Z, Liu QY, Xiong S, Qian CW, Zeng FL, Zhang PZ, Yang CR, Zhang YJ, Xu J, Kitazato K, Wang YF.
  • Journal Title: Antiviral Res Volume: 89(1) Pages: 98-108
  • Peer Reviewed
• [Journal Article] The C-terminus of MIP-T3 protein is required for ubiquitin-proteasome-mediated degradation in human cells (2011)
  • Author(s): Guo C-W, Liu G, Xiong S, Ge F, Fuse T, Wang Y-F, and Kitazato K*
  • Journal Title: FEBS Lett Volume: 585(9) Pages: 1350-6
  • NAID: 120006985117
  • Peer Reviewed
• [Journal Article] Notoginsenoside ST-4 inhibits virus penetration of herpes simplex virus in vitro J. Asian Nat (2011)
  • Author(s): Pei Y, Du Q, Liao; Chen ZP, Wang; Yang C-R, Kitazato K, Zhang Y-J, Wang Y-F
  • Journal Title: Prod. Res. Volume: 13(6) Pages: 498-501
  • Peer Reviewed
• [Journal Article] Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus (2011)
  • Author(s): Liu G, Xiong S, Xiang Y-F, Guo C-W, Ge F, Yang C-R, Zhang Y-J, Wang Y-F, and Kitazato K*
  • Journal Title: Arch. Virol. Volume: 156(8) Pages: 1359-69
  • NAID: 120006985126
  • Peer Reviewed
• [Journal Article] Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro. (2011)
  • Author(s): Pei Y, Chen ZP, Ju HQ, Komatsu M,Ji YH, Liu G, Guo CW, Zhang YJ, Yang CR, Wang Y-F, Kitazato K
  • Journal Title: Biochem Biophys Res Commun. Volume: 405(2) Pages: 186-91
  • Peer Reviewed
• [Journal Article] Activity of 1,2,4,6-Tetra-O-galloyl-β- d-glucose from Phyllanthus emblica L. (Euphorbiaceae) (2011)
  • Author(s): Xiang Y, Pei Y, Qu C, Lai Z, Ren Z, Yang K, Xiong S, Zhang Y, Yang C, Wang D, Liu Q, Kitazato K*, Wang Y-F.
  • Journal Title: Phytother Res. Volume: 25(7) Pages: 975-82
  • Peer Reviewed
• [Journal Article] Pentagalloylglucose downregulates cofilin1 and inhibits HSV-1 infection (2011)
  • Author(s): Pei Y, Xiang YF, Chen JN, Lu CH, Hao J, Du Q, Lai CC, Qu C, Li S, Ju HQ, Ren Z, Liu QY, Xiong S, Qian CW, Zeng FL, Zhang PZ, Yang CR, Zhang YJ, Xu J, Kitazato K*, Wang Y-F.
  • Journal Title: Antiviral Res. Volume: 89(1) Pages: 98-108
  • Peer Reviewed
• [Journal Article] Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells (2011)
  • Author(s): Ge F, Zhang L, Tao SC, Kitazato K, Zhang ZP, Zhang XE, Bi LJ.
  • Journal Title: J Proteome Res. Volume: 10(2) Pages: 845-55
  • Peer Reviewed
• [Journal Article] Proteomic analysis of multiple myeloma: Current status and future perspectives (2011)
  • Author(s): Ge F, Bi LJ, Tao SC, Xu XD, Zhang ZP, Kitazato K, Zhang XE
  • Journal Title: Proteomics Clin Appl. Volume: 5(1-2) Pages: 30-7
  • Peer Reviewed
• [Journal Article] Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus (2011)
  • Author(s): Liu G, et al
  • Journal Title: Arch.Virol Volume: 156(8) Issue: 8 Pages: 1359-1369
  • DOI: 10.1007/s00705-011-0989-9
  • Peer Reviewed
• [Journal Article] Notoginsenoside ST-4 inhibits virus penetration of herpes simplex virus in vitro (2011)
  • Author(s): Pei Y
  • Journal Title: J Asian Nat Prod Res Volume: 13(6) Issue: 06 Pages: 498-504
  • DOI: 10.1080/10286020.2011.571645
  • Peer Reviewed
• [Journal Article] Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro (2011)
  • Author(s): Pei, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 405 Pages: 186-191
  • Peer Reviewed
• [Journal Article] The C-terminus of MIP-T3 protein is required for ubiquitin-proteasome-mediated degradation in human cells (2011)
  • Author(s): Guo, et al
  • Journal Title: FEBS Letters Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] A Cys/Ser mutation of NDPK-A stabilizes its oligomerization state and enhances its activity (2010)
  • Author(s): Chen Y, Qian C, Guo C, Ge F, Zhang X, Gao X, Shen S, Lian B, Kitazato K, Wang Y, Xiong S.
  • Journal Title: J Biochem Volume: 148(2) Pages: 49-55
  • NAID: 10027877486
  • Peer Reviewed
• [Journal Article] Proteomic analysis reveals novel binding partners of MIP-T3 in human cells. (2010)
  • Author(s): Guo C, Xiong S, Liu G, Wang YF, He QY, Zhang XE, Zhang ZP, Ge F, Kitazato K.
  • Journal Title: Proteomics Volume: 10(12) Pages: 2337-47
  • Peer Reviewed
• [Journal Article] The antiviral protein cyanovirin-N: the current state of its production and applications (2010)
  • Author(s): Xiong S, Fan J, Kitazato K.
  • Journal Title: Appl Microbiol Biotechnol Volume: 86(3) Pages: 805-12
  • NAID: 120006984595
  • Peer Reviewed
• [Presentation] Autophagy is involved in viral RNA synthesis of influenza A virus (2012)
  • Author(s): Kaio Kitazato, Ge Liu, Chao-Wan Guo, Mei-Gong Zhong, Yang-Fei Xiang,Hu Ge, Yu Wang, Masaaki Komatsu, Tamotsu Yoshimori, Jun Xu and Yi-Fei Wang
  • Organizer: 第6回オートファジー国際シンポジウム(ISA 2012)
  • Place of Presentation: Okinawa
• [Presentation] Autophagy is involved in viral protein expression of influenza A virus (2012)
  • Author(s): Kaio Kitazato, Ge Liu, Chao-Wan Guo, Mei-Gong Zhong, Masaaki Komatsu, Tamotsu Yoshimori, and Yi-Fei Wang
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] ポリフェノールによるインフルエンザウイルス感染阻害分子メカニズムの解析 (2012)
  • Author(s): 劉 格 、葛 虎 、向 陽 飛 、郭 朝 万 、王 一飛、徐 峻、北里 海雄
  • Organizer: 第29回薬学会九州支部大会
  • Place of Presentation: 熊本
• [Presentation] インフルエンザウイルス感染複製におけるオートファジーの役割解析 (2012)
  • Author(s): 北里 海雄、劉 格、郭 朝万、王 宇、葛 虎、鐘 媚共、王 一飛、徐 峻
  • Organizer: 第29回薬学会九州支部大会
  • Place of Presentation: 熊本
• [Presentation] Autophagy is involved in viral RNA synthesis of influenza A virus (2012)
  • Author(s): Kitazato K., et al
  • Organizer: 第6回オートファジー国際シンポジウム（ISA2012）
  • Place of Presentation: 沖縄
• [Presentation] インフルエンザウイルス感染複製におけるオートファジーの役割解析 (2012)
  • Author(s): 北里海雄、劉格、郭朝万等
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本
• [Presentation] ポリフェノールによるインフルエンザウイルス感染阻害分子メカニズムの解析 (2012)
  • Author(s): 劉格、葛虎、向陽飛、郭朝万, 等
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本
• [Presentation] The C-terminus of MIP-T3 protein is required for ubiquitin-proteasome-mediated degradation in human cells (2011)
  • Author(s): Chao-Wan Guo
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-12-16
• [Presentation] ヒト細胞における鞭毛輸送タンパク質MIP-T3の分子機能解析 (2011)
  • Author(s): 郭朝万
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-12-10
• [Presentation] ペンタガロイルグルコース(PGG)の抗インフルエンザウイルス作用機序の解析 (2011)
  • Author(s): 劉格
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-12-10
• [Presentation] Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus (2011)
  • Author(s): Ge Liu
  • Organizer: 国際ウイルス学会(IUMS2011)
  • Place of Presentation: 札幌(シンポジウム)
  • Year and Date: 2011-09-16
• [Presentation] Autophagy is involved in viral protein expression of influenza A virus (2011)
  • Author(s): Kaio Kitazato
  • Organizer: 国際ウイルス学会(IUMS2011)
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-13
• [Presentation] ウイルス感染複製におけるオートファジーの役割 (2011)
  • Author(s): 北里海雄
  • Organizer: オートファジー研究会
  • Place of Presentation: 掛川ヤマハリゾートつま恋
  • Year and Date: 2011-01-14
• [Presentation] Autophagy is involved in viral protein expression of influenza A virus (2011)
  • Author(s): Kaio Kitazato, Ge Liu, Chao-Wan Guo, Yang-Fei Xiang, Masaaki Komatsu, Tamotsu Yoshimori, and Yi-Fei Wang
  • Organizer: 第15回国際ウイルス学会(IUMS 2011)
  • Place of Presentation: Sapporo
• [Presentation] Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus (2011)
  • Author(s): Ge Liu, Sheng Xiong, Yang-Fei Xiang, Chao-Wan Guo, Feng Ge, Chong-Ren Yang, Ying-Jun Zhang, Yi-Fei Wang, and Kaio Kitazato
  • Organizer: 第15回国際ウイルス学会(IUMS 2011)
  • Place of Presentation: Sapporo
• [Presentation] ペンタガロイルグルコース(PGG)の抗インフルエンザウイルス作用機序の解析 (2011)
  • Author(s): 劉 格、向陽飛、郭朝万、張穎君、王一飛、北里海雄
  • Organizer: 第28回薬学会九州支部大会
  • Place of Presentation: 福岡
• [Presentation] ヒト細胞における鞭毛輸送タンパク質MIP-T3の分子機能解析 (2011)
  • Author(s): 郭朝万、劉格、北里海雄
  • Organizer: 第28回薬学会九州支部大会
  • Place of Presentation: 福岡
• [Presentation] The C-terminus of MIP-T3 protein is required for ubiquitinproteasome-mediated degradation in human cells (2011)
  • Author(s): Chao-Wan Guo, Ge Liu, and Kaio Kitazato*
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] The C-terminus of MIP-T3 protein is required for ubiquitin-proteasome mediated degradation in human cells (2010)
  • Author(s): Guo, et al
  • Organizer: 日本薬学会九州支部会
  • Place of Presentation: 長崎(薬学部)
  • Year and Date: 2010-12-11
• [Presentation] Virucidal efficacy of 1,2,3,4,6-penta-O-galloyl-β-D-glucose(PGG)on influenza A virus (2010)
  • Author(s): Liu, et al
  • Organizer: 日本薬学会九州支部会
  • Place of Presentation: 長崎(薬学部)
  • Year and Date: 2010-12-11
• [Presentation] In vitro Anti-influenza virus activity of pentagalloylglucose(PGG) and its mode of action (2010)
  • Author(s): Liu, et al
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 徳島(阿波銀ホール)
  • Year and Date: 2010-11-09
• [Presentation] ペンタガロイルグルコース(PGG)の抗インフルエンザウイルス活性と作用機序の解析 (2010)
  • Author(s): 劉格、熊盛、郭朝万、葛峰、張頴君、王一飛、北里海雄
  • Organizer: 第20回抗ウイルス療法研究会
  • Place of Presentation: 熊本
• [Presentation] In vitro Anti-influenza virus activity ofPentagalloylglucose (PGG) and its mode of action (2010)
  • Author(s): Ge Liu, Sheng Xiong, Yangfei Xiang, Chaowan Guo, Feng Ge, Yingjun Zhang, YifeiWang, and Kaio Kitazato
  • Organizer: 第58回日本ウイルス学会
  • Place of Presentation: 徳島
• [Presentation] ProteomicAnalysis Reveals Novel Binding Partners of MIP-T3 in Human Cells (2010)
  • Author(s): Chao-Wan Guo, Feng Ge, Sheng Xiong, Ge Liu, and Kaio Kitazato*
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] The C-terminusof MIP-T3 protein is required for ubiquitin-proteasome mediated degradation in human cells (2010)
  • Author(s): Chao-Wan Guo, Feng Ge, Sheng Xiong, Ge Liu, and Kaio Kitazato*
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎
• [Presentation] Virucidal efficacy of1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG) against influenza A virus (2010)
  • Author(s): Ge Liu,Yang-Fei Xiang, Sheng Xiong, Chao-Wan Guo, Feng Ge, Chong-Ren Yang,Ying-Jun Zhang, Yi-Fei Wang, and Kaio Kitazato*
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎