Molecular dissection of HBV evasion from host antiviral responses

• Project/Area Number: 26860306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKAWA Kei 横浜市立大学, 医学部, 助教 (20580046)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ウイルス-宿主相互作用 / ピロトーシス / 宿主-ウイルス相互作用

Outline of Final Research Achievements

Accumulating evidence strongly suggests the ineffectiveness of interferon (IFN) therapy against chronic hepatitis B virus (HBV) infection. In this study, we demonstrate that HBV surface protein (HBs) plays a crucial role in counteracting the IFN-induced antiviral response mediated by an antiviral membrane protein tetherin. HBs can interact with tetherin via its transmembrane domain thereby inhibiting its dimerization and antiviral activity. The expression of a tetherin mutant devoid of the HBs-binding domain promoted a prominent restriction of HBV particle production. that eventually resulted in the alleviation of caspase-1-mediated cytotoxicity and interleukin-1β secretion in induced pluripotent stem cell-derived hepatocytes. Our current study thus reveals a previously un-described molecular link between HBV and tetherin during the course of an IFN-induced antiviral response.

Research Products

• [Int'l Joint Research] National University of Singapore(Singapore)
• [Journal Article] Cooperative Orthogonal Macromolecular Assemblies with Broad Spectrum Antiviral Activity, High Selectivity, and Resistance Mitigation (2016)
  • Author(s): Ichiyama K, Yang C, Chandrasekaran L, Liu S, Rong L, Zhao Y, Gao S, Lee A, Ohba K, Suzuki Y, Yoshinaka Y, Shimotohno K, Miyakawa K, Ryo A, Hedrick J, Yamamoto N, Yang YY
  • Journal Title: Macromolecules Volume: 49 Issue: 7 Pages: 2618-2629
  • DOI: 10.1021/acs.macromol.6b00091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular dissection of HBV evasion from restriction factor tetherin: A new perspective for antiviral cell therapy. (2015)
  • Author(s): Miyakawa K, Matsunaga S, Watashi K, Sugiyama M, Kimura H, Yamamoto N, Mizokami M, Wakita T, Ryo A.
  • Journal Title: Oncotarget Volume: 6 Pages: 21840-21852
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction. (2015)
  • Author(s): Miyakawa K, Matsunaga S, Kanou K, Matsuzawa A, Morishita R, Kudoh A, Shindo K, Yokoyama M, Sato H, Kimura H, Tamura T, Yamamoto N, Ichijo H, Takaori-Kondo A, Ryo A.
  • Journal Title: Nature Communications Volume: 6:6945 Issue: 1 Pages: 6945-6945
  • DOI: 10.1038/ncomms7945
  • NAID: 120005745628
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Molecular dissection of HBV evasion from restriction factor tetherin (2015)
  • Author(s): Miyakawa K, Matsunaga S, Watashi K, Sugiyama M, Mizokami M, Wakita T, Ryo A
  • Organizer: International Meeting on Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim, Germany
  • Year and Date: 2015-10-04
  • Int'l Joint Research
• [Presentation] Development of anti-HBs monoclonal antibody targeting HBs-NTCP interaction (2015)
  • Author(s): Matsunaga S, Miyakawa K, Watashi K, Sugiyama M, Mizokami M, Wakita T, Ryo A
  • Organizer: International Meeting on Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: Bad Nauheim, Germany
  • Year and Date: 2015-10-04
  • Int'l Joint Research
• [Presentation] 宿主防御因子Tetherin/BST2によるB型肝炎ウイルス感染抑制とその回避機構の解明 (2014)
  • Author(s): 宮川 敬, 松永智子, 渡士幸一, 杉山真也, 溝上雅史, 脇田隆字, 梁 明秀
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] B型肝炎ウイルスのコアタンパク質(HBc)に対するマウスモノクローナル抗体の作製と解析 (2014)
  • Author(s): 山岡 悠太郎, 宮川 敬, 松永 智子, 宮本摩由, 黒山浩之, 千室智之, 梁 明秀
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-11-10 – 2014-11-12