Mechanisms for ATP supply to the site of virus replication in cells

• Project/Area Number: 26670224
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Suzuki Tetsuro 浜松医科大学, 医学部, 教授 (00250184)
• Co-Investigator(Kenkyū-buntansha): ITO MASAHIKO 浜松医科大学, 医学部, 助教 (50385423)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: C型肝炎ウイルス / ウイルス複製 / ATP / ミトコンドリア / 複製

Outline of Final Research Achievements

Replication of the virus genome is a physiological mechanism that is known to require energy for operations. However, mechanisms for how ATP, the major energy currency of living cells, can be recruited to the site for the viral replication are unknown.
In this study, since mitochondria play a central role in ATP metabolism and is known to localize near the membranous web in certain conditions, we analyzed the subcellular localization of the FRET and fluorescence signals detected in cells expressing HCV-ATeam subgenome with that of mitochondria. Possible viral replication complexes, foci reflecting high ATP levels, did not co-localize with, but were localized adjacent to mitochondria in the viral replicating cells. This may suggest that ATP can be directly supplied from mitochondria to the sites of viral RNA replication in cells.

Research Products

• [Journal Article] Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B (2016)
  • Author(s): Kong L, Fujimoto A, Nakamura M, Aoyagi H, Matsuda M, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, Suzuki T, Sakamaki Y, Ichinose S, Suzuki T, Wakita T, Aizaki H
  • Journal Title: J Virol Volume: 90 Issue: 6 Pages: 3093-3111
  • DOI: 10.1128/jvi.01540-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Single-domain Intrabodies against HCV Core Inhibit Viral Propagation and Core-induced NF-κB Activation (2016)
  • Author(s): Suzuki R, Saito K, Matsuda M, Sato M, Kanegae Y, Shi G, Watashi K, Aizaki H, Chiba J, Saito I, Wakita T, Suzuki T
  • Journal Title: J Gen Virol Volume: 印刷中 Issue: 4 Pages: 887-892
  • DOI: 10.1099/jgv.0.000423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of the 3' Untranslated Region in Encapsidation of the Hepatitis C Virus (2016)
  • Author(s): Shi G, Ando T, Suzuki R, Matsuda M, Nakashima K, Ito M, Omatsu T, Oba M, Ochiai H, Kato T, Mizutani T, Sawasaki T, Wakita T, Suzuki T.
  • Journal Title: PLoS Pathog Volume: 12(2) Issue: 2 Pages: e1005441-e1005441
  • DOI: 10.1371/journal.ppat.1005441
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model (2015)
  • Author(s): Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
  • Journal Title: J Virol Volume: 89 Issue: 9 Pages: 4866-4879
  • DOI: 10.1128/jvi.03676-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry. (2015)
  • Author(s): 123.Park C, Min S, Park EM, Lim YS, Kang S, Suzuki T, Shin EC, Hwang SB.
  • Journal Title: J. Virol. Volume: 89 Issue: 19 Pages: 10073-10086
  • DOI: 10.1128/jvi.01707-15
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis is a potential antiviral strategy against hepatitis C virus (2015)
  • Author(s): Kyoko Saito, Yoshitaka Shirasago, Tetsuro Suzuki, Hideki Aizaki, Kentaro Hanada, Takaji Wakita, Masahiro Nishijima, Masayoshi Fukasawa
  • Journal Title: J. Virol. Volume: 89 Issue: 4 Pages: 2220-2232
  • DOI: 10.1128/jvi.03385-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of self-assembled virus-like particles of Merkel cell polyomavirus. (2015)
  • Author(s): Li TC, Iwasaki K, Katano H, Kataoka M, Nagata N, Kobayashi K, Mizutani T, Takeda N, Wakita T, Suzuki T.
  • Journal Title: PLOS ONE Volume: 10 Issue: 2 Pages: 524-531
  • DOI: 10.1371/journal.pone.0115646
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of Hepatitis C Virus NS5A Hyperphosphorylation Mediated by Casein Kinase I-α in Infectious Virus Production. (2014)
  • Author(s): Masaki T, Matsunaga S, Takahashi H, Nakashima K, Kimura Y, Ito M, Matsuda M, Murayama A, Kato T, Hirano H, Endo Y, Lemon SM, Wakita T, Sawasaki T, Suzuki T
  • Journal Title: J Virol Volume: 88(13) Issue: 13 Pages: 7541-55
  • DOI: 10.1128/jvi.03170-13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alternative endocytosis pathway for productive entry of hepatitis C virus. (2014)
  • Author(s): Matsuda M, Suzuki R, Kataoka C, Watashi K, Aizaki H, Kato N, Matsuura Y, Suzuki T, Wakita T
  • Journal Title: J Gen Virol. Volume: 95(Pt 12) Issue: 12 Pages: 2658-67
  • DOI: 10.1099/vir.0.068528-0
  • Peer Reviewed / Open Access