Mechanistic analysis about the association of IL28B genetic polymorphism with IFN sensitivity in HCV infected patients

• Project/Area Number: 23790502
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: FUKUHARA Takasuke 大阪大学, 微生物病研究所, 助教 (70598739)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: C型肝炎ウイルス / 肝臓移植 / IL28B / IFN感受性

Research Abstract

In this study, we evaluated the importance of IL28B genetic polymorphism in IFN sensitivity for recurrent hepatitis C after liver transplantation. Interestingly, genetic variability in both recipients and donors was significantly associated with IFN sensitivity, suggesting crosstalk between lymphocyte and HCV-infected hepatocyte participates in the IFN sensitivity. In addition, we established allele-specific IL28B knockout Huh7 cells by using chimeric nucleases.

Research Products

• [Journal Article] Role of miR-122 and lipid metabolism in HCV infection. (2013)
  • Author(s): 福原崇介
  • Journal Title: Journal of Gastroenterology Volume: 48(2) Issue: 2 Pages: 169-76
  • DOI: 10.1007/s00535-012-0661-5
  • NAID: 10031156302
  • Peer Reviewed
• [Journal Article] Role of miR-122 and lipid metabolism in HCV infection (2012)
  • Author(s): Fukuhara T, et al
  • Journal Title: J Gastroenterol Volume: (in press)
  • NAID: 10031156302
• [Journal Article] Establishment of a novel permissive cell line for propagation of hepatitis C virus by the expression of microRNA122 (2012)
  • Author(s): Kambara H., Fukuhara T., Shiokawa M., Ono C., Ohara Y., Kamitani W., and Matsuura Y.
  • Journal Title: J. Virol Volume: 86 Issue: 15 Pages: 1382-1393
  • DOI: 10.1128/jvi.00567-12
  • Peer Reviewed
• [Journal Article] Establishment of a novel permissive cell line for the propagation of hepatitis C virus by expression of microRNA miR122 (2012)
  • Author(s): Kambara H, Fukuhara T, et al
  • Journal Title: J Virol. Volume: 86 Issue: 3 Pages: 1382-1393
  • DOI: 10.1128/jvi.06242-11
  • Peer Reviewed
• [Journal Article] CD44 participates in IP-10 induction in cells in which hepatitis C virus RNA is replicating, through an interaction with Toll-like receptor 2 and hyaluronan. (2012)
  • Author(s): Abe T
  • Journal Title: J Virol. Volume: 86 Issue: 11 Pages: 6159-6170
  • DOI: 10.1128/jvi.06872-11
  • Peer Reviewed
• [Journal Article] Baculovirus GP64-mediated entry into mammalian cells. (2012)
  • Author(s): Kataoka C, Kaname Y, Taguwa S AbeT, Fukuhara T, et al
  • Journal Title: J Virol Volume: 86 Issue: 5 Pages: 2610-2620
  • DOI: 10.1128/jvi.06704-11
  • Peer Reviewed
• [Journal Article] Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment (2012)
  • Author(s): Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y, Fukuhara T, et al
  • Journal Title: J Hepatol Volume: (in press)
• [Journal Article] V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation (2012)
  • Author(s): Toshima T, Taketomi A, Ikegami T, Fukuhara T, et al
  • Journal Title: Transplantation Volume: 15 Issue: 9 Pages: 929-935
  • DOI: 10.1097/tp.0b013e3182488bd8
  • Peer Reviewed
• [Journal Article] Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype (2012)
  • Author(s): Motomura T, Koga E, Taketomi A, Fukuhara T, et al
  • Journal Title: Hepatol Res Volume: 42 Issue: 3 Pages: 288-295
  • DOI: 10.1111/j.1872-034x.2011.00927.x
  • NAID: 10031144238
  • Peer Reviewed
• [Journal Article] Intracellular delivery of serum-derived hepatitis C virus (2011)
  • Author(s): Fukuhara T, et al
  • Journal Title: Microbes Infect Volume: 13 Issue: 4 Pages: 405-12
  • DOI: 10.1016/j.micinf.2011.01.005
  • Peer Reviewed
• [Journal Article] Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA (2011)
  • Author(s): Hiroshi Katoh
  • Journal Title: Journal of Virology Volume: 85(21) Issue: 21 Pages: 10976-10988
  • DOI: 10.1128/jvi.00846-11
  • Peer Reviewed
• [Journal Article] The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation : significant lessons from a dual graft case (2011)
  • Author(s): Motomura T., et al
  • Journal Title: Am J Transplant Volume: 11 Issue: 6 Pages: 1325-9
  • DOI: 10.1111/j.1600-6143.2011.03537.x
  • Peer Reviewed
• [Journal Article] Involvement of cyclophilin B in the replication of Japanese encephalitis virus (2011)
  • Author(s): Kambara H., Tani H., Mori Y., Abe T., Katoh H., Fukuhara T., Taguwa S., Moriishi K, and Matsuura Y.
  • Journal Title: Virology Volume: 412 Issue: 1 Pages: 211-219
  • DOI: 10.1016/j.virol.2011.01.011
  • Peer Reviewed
• [Presentation] 一般講演:HCV感染の肝細胞指向性はmiR-122の発現と脂質代謝によって規定される (2012)
  • Author(s): 福原崇介、塩川舞、小野慎子、山本聡美、寒原裕登、加藤大志、岡本徹、奥崎大介、松浦善治
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] 一般講演:C型肝炎ウイルスの粒子産生に関与するヒト肝細胞特異因子の解析と新規感受性細胞株の樹立 (2012)
  • Author(s): 塩川舞、福原崇介、小野慎子、山本聡美、岡本徹、松浦善治
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] C型肝炎ウイルスに感受性を示すマウス肝臓細胞株の樹立 (2012)
  • Author(s): 小野慎子、福原崇介、塩川舞、岡本徹、松浦善治: 一般講演
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] 一般講演:HuH-7由来オーバル様細胞におけるHCV感受性の解析 (2012)
  • Author(s): 伊藤昌彦、鈴木亮介、福原崇介、松浦善治、脇田隆字、鈴木哲朗
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] パネルディスカッション:HCVの非肝臓系細胞株に対する感染培養システムの確立と肝外病変成立に関わる宿主因子の同定 (2012)
  • Author(s): 福原崇介、本村貴志、松浦善治
  • Organizer: JDDW
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-11
• [Presentation] 一般講演:C型肝炎ウイルスの肝細胞指向性におけるmiR-122と脂質代謝の役割 (2012)
  • Author(s): 福原崇介
  • Organizer: 第11回Hepatitis Expert Meeting
  • Place of Presentation: 東京
  • Year and Date: 2012-08-25
• [Presentation] Identification of Host Factors Interact with Hepatitis B virus X Protein (2012)
  • Author(s): Kouwaki T, Pham DN, Fukuhara T, Okamoto T, and Matsuura Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Quasispecies Plays an Important Role in Cell Tropism of Hepatitis C Virus (2012)
  • Author(s): Fukuhara T, Motomura T, Shiokawa M, Ono C, Kambara H, Okamoto T, Shirabe K, Maehara Y, and Matsuura Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] nvolvement of Human Liver-specific Factors in a Complete Propagation of Hepatitis C Virus (2012)
  • Author(s): Shiokawa M, Fukuhara T, Ono C, Okamoto T, and Matsuura Y.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Establishment of Mouse Liver Cell Lines Susceptible to Hepatitis C Virus Infection (2012)
  • Author(s): Ono C, Fukuhara T, Shiokawa M, Okamoto T, and Matsuura Y
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] MiR-122 expression and lipid metabolism participate in the cell tropism of HCV infection (2012)
  • Author(s): Fukuhara T, Shiokawa M, Arimoto M, Ono C, Katoh H, Kambara H, Okamoto T, and Matsuura Y.
  • Organizer: 19th International Meeting on HCV and Related Viruses
  • Place of Presentation: Venice, Italy
• [Presentation] miR-122 expression and lipid metabolism participate in cell tropism of hepatitis C virus infection. The American Society for Virology (2012)
  • Author(s): Fukuhara T, Kambara H, Shiokawa M, Ono C, Kato H, Okamoto T, and Matsuura Y
  • Organizer: 31th Annual Meeting
  • Place of Presentation: University of Wisconsin-Madison
• [Presentation] HCVの非肝臓系細胞株に対する感染培養システムの確立と肝外病変成立に関わる宿主因子の同定 (2012)
  • Author(s): 福原崇介
  • Organizer: JDDW2012
  • Place of Presentation: 神戸
• [Presentation] 肝移植症例におけるIL28B、ITPAおよびMICA遺伝子多型の検討 (2011)
  • Author(s): 福原崇介
  • Organizer: 広島肝臓プロジェクト研究センターシンポジウム
  • Place of Presentation: ホテルグランビア広島