Access & Contact

Project Chief.
Kunitada Shimotohno

Research Center for Hepatitis and Immunology National Center for Global Health and Medicine

Address:
1-7-1 Kohnodai Ichikawa 272-8516, Chiba, Japan

phone:
81-47-375-4742 (ext 1435)
81-47-375-4750 (direct)

fax:
81-47-375-4766

mail address:
kunitada.shimotohno@it-chiba.ac.jp


Recent Publications

  1. Ujino S, Nishitsuji H, Hishiki T, Sugiyama K, Takaku H, Shimotohno K. Hepatitis C virus utilizes VLDLR as a novel entry pathway. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):188-193.
  2. Nishitsuji H, Ujino S, Shimizu Y, Harada K, Zhang J, Sugiyama M, Mizokami M, Shimotohno K. Novel reporter system to monitor early stages of the hepatitis B virus life cycle. Cancer Sci. 2015 Nov;106(11):1616-1624.
  3. Gondar V, Molina-Jiménez F, Hishiki T, García-Buey L, Koutsoudakis G, Shimotohno K, Benedicto I, Majano PL. Apolipoprotein E, but Not Apolipoprotein B, Is Essential for Efficient Cell-to-Cell Transmission of Hepatitis C Virus. J Virol. 2015 Oct;89(19):9962-9973.
  4. Tsukimoto A, Sugiyama R, Abe M, Nishitsuji H, Shimizu Y, Shimotohno K, Kawai G, Takaku H. A new role for PGA1 in inhibiting hepatitis C virus-IRES-mediated translation by targeting viral translation factors. Antiviral Res. 2015 May;117:1-9.
  5. Arimoto KI, Hishiki T, Kiyonari H, Abe T, Cheng C, Yan M, Fan JB, Futakuchi M, Tsuda H, Murakami Y, Suzuki H, Zhang DE, Shimotohno K. Murine Herc6 Plays a Critical Role in Protein ISGylation In Vivo and Has an ISGylation-Independent Function in Seminal Vesicles.J Interferon Cytokine Res. 2014 Nov 19. [Epub ahead of print]
  6. Shimizu Y, Nishitsuji H, Marusawa H, Ujino S, Takaku H, Shimotohno K. The RNA-editing enzyme APOBEC1 requires heterogeneous nuclear ribonucleoprotein Q isoform 6 for efficient interaction with interleukin-8 mRNA.J Biol Chem. 289(38): 26226-26238, 2014
  7. Nakai M, Seya T, Matsumoto M, Shimotohno K, Sakamoto N, Aly HH.The J6JFH1 Strain of Hepatitis C Virus Infects Human B-Cells with Low Replication Efficacy. Viral Immunol. 2014 May 22.
  8. Tsugawa Y, Kato H, Fujita T, Shimotohno K, Hijikata M. Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection. PLoS One. 2014 Feb 26;9(2):e89869.
  9. Abe Y, Aly HH, Hiraga N, Imamura M, Wakita T, Shimotohno K, Chayama K, Hijikata M.Thromboxane A2 Synthase Inhibitors Prevent Production of Infectious Hepatitis C Virus in Mice With Humanized Livers. Gastroenterology. 145: 658-667, 2013
  10. Nishitsuji H, Funami K, Shimizu Y, Ujino S, Sugiyama K, Seya T, Takaku H, Shimotohno K. Hepatitis C Virus Infection Induces Inflammatory Cytokines and Chemokines Mediated by the Cross Talk between Hepatocytes and Stellate Cells. J. Viol 87: 8169-8178, 2013
  11. Kuroki M, Ariumi Y, Hijikata M, Ikeda M, Dansako H, Wakita T, Shimotohno K, Kato N., PML tumor suppressor protein is required for HCV production. Biochem Biophys Res Commun. 430(2): 592-597, 2013.
  12. Weng L, Tian X, Gao Y, Watashi K, Shimotohno K, Wakita T, Kohara M, Toyoda T. Different mechanisms of hepatitis C virus RNA polymerase activation by cyclophilin A and B in vitro. Biochim Biophys Acta. 1820(12):1886-1892, 2012
  13. Hirata Y, Ikeda K, Sudoh M, Tokunaga Y, Suzuki A, Weng L, Ohta M, Tobita Y, Okano Ozeki K, Kawasaki K, Tsukuda T, Katsume A, Aoki Y, Umehara T, Sekiguchi S, Toyoda T, Shimotohno K, Soga T, Nishijima M, Taguchi R, Kohara M. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis. PLoS Pathog. 8(8):e1002860, 2012
  14. Aly HH, Shimotohno K, Hijikata M, Seya T. In vitro models for analysis of the hepatitis C virus life cycle. Microbiol Immunol. 56(1):1-9. 2012
  15. Ujino S, Nishitsuji H, Sugiyama R, Suzuki H, Hishiki T, Sugiyama K, Shimotohno K, Takaku H. The interaction between human initiation factor eIF3 subunit c and heat-shock protein 90: A necessary factor for translation mediated by the hepatitis C virus internal ribosome entry site. Virus Res. 163: 390-395,2012
  16. Shimizu Y, Takayuki Hishiki T, Ujino S, Funami K, Shimotohno K, Lipoprotein component associated with hepatitis C virus is essential for virus infectivity. Current Opinion in Virology 1:19–26, 2011
  17. Aly HH, Oshiumi H, Shime H, Matsumoto M, Wakita T, Shimotohno K, Seya T. Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV). PLoS One. 6(6):e21284, 2011
  18. Onomoto K, Morimoto S, Kawaguchi T, Toyoda H, Tanaka M, Kuroda M, Uno K, Kumada T, Matsuda F, Shimotohno K, Fujita T, Murakami Y. Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C. PLoS One. 6(5):e19799, 2011
  19. Morohashi K, Sahara H, Watashi K, Iwabata K, Sunoki T, Kuramochi K, Takakusagi K, Miyashita H, Sato N, Tanabe A, Shimotohno K, Kobayashi S, Sakaguchi K, Sugawara F. Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B. PLoS One. 6(4):e18285. 2011
  20. Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, Kosaka N, Ochiya T, Shimotohno K. The Progression of Liver Fibrosis Is Related with Overexpression of the miR-199 and 200 Families. PLoS One. 2011 Jan 24;6(1):e16081.
  21. Oshiumi H, Ikeda M, Matsumoto M, Watanabe A, Takeuchi O, Akira S, Kato N, Shimotohno K, Seya T. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction. PLoS One. 2010 Dec 8;5(12):e14258.
  22. Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, Shimotohno K. Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C. BMC Med Genomics. 3(1): 48, 2010.
  23. Weng L, Hirata Y, Arai M, Kohara M, Wakita T, Watashi K, Shimotohno K, He Y, Zhong J, Toyoda T. Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner. J Virol. 84(22):11761-11770, 2010.
  24. Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fujimoto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K. Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms. J Virol. 84(22): 12048-12057, 2010
  25. Shimizu Y, Hishiki T, Sugiyama K, Ogawa K, Funami K, Kato A, Ohsaki Y, Fujimoto T, Takaku H, Shimotohno K. Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus (HCV) through their catalytic activities on HCV-associated lipoproteins. Virology. 407(1):152-915, 2010
  26. Arimoto K, Funami K, Saeki Y, Tanaka K, Okawa K, Takeuchi O, Akira S, Murakami Y, Shimotohno K. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc Natl Acad Sci U S A. 107(36): 15856-15861, 2010
  27. Ujino S, Yamaguchi S, Shimotohno K, Takaku H.Combination therapy for hepatitis C virus with heat-shock protein 90 inhibitor 17-AAG and proteasome inhibitor MG132. Antivir Chem Chemother. 20(4): 161-167, 2010.
  28. Murata T, Sato Y, Nakayama S, Kudoh A, Iwahori S, Isomura H, Tajima M, Hishiki T, Ohshima T, Hijikata M, Shimotohno K, Tsurumi T. TORC 2, a coactivator of CREB, promotes Epstein-Barr virus reactivation from latency through interaction with viral BZLF1 protein. J Biol Chem. 284(12): 8033-8041, 2009.
  29. Ujino S, Yamaguchi S, Shimotohno K, Takaku H. Heat-shock protein 90 is essential for stabilization of the hepatitis C virus non-structural protein NS3. J Biol Chem. 284: 6841-6846, 2009
  30. Ikejiri M, Ohshima T, Fukushima A, Shimotohno K, Maruyama T. Synthesis and anti-HCV activity of 2′,5′-deoxy-5′-phenacyladenosine analogs. Nucleic Acids Symp Ser (Oxf). 53:103-104, 2009
  31. Goto K, Watashi K, Inoue D, Hijikata M, Shimotohno K. Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor. Cancer Sci. 100: 1943-1950, 2009
  32. Ogawa K, Hishiki T, Shimizu Y, Funami K, Sugiyama K, Miyanari Y, Shimotohno K. Hepatitis C virus utilizes lipid droplet for production of infectious virus. Proc Jpn Acad Ser B Phys Biol Sci. 85(7): 217-228, 2009
  33. Aly HH, Qi Y, Atsuzawa K, Usuda N, Takada Y, Mizokami M, Shimotohno K, Hijikata M. Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus. Hepatology. 50(3): 689-696, 2009.
  34. Sugiyama K, Suzuki K, Nakazawa T, Funami K, Hishiki T, Ogawa K, Saito S, Shimotohno KW, Suzuki T, Shimizu Y, Tobita R, Hijikata M, Takaku H, Shimotohno K. Genetic analysis of hepatitis C virus with defective genome and its infectivity in vitro. J Virol. 83(13): 6922-6928, 2009
  35. Okamoto M, Sakai M, Goto Y, Salim MT, Baba C, Goto K, Watashi K, Shimotohno K, Baba M. Anti-bovine viral diarrhoea virus and hepatitis C virus activity of the cyclooxygenase inhibitor SC-560. Antivir Chem Chemother.20(1): 47-54, 2009.
  36. Ikejiri M, Ohshima T, Fukushima A, Shimotohno K, Maruyama T. Synthesis and anti-HCV activity of 2′,5′-deoxy-5′-phenacyladenosine analogs. Nucleic Acids Symp Ser (Oxf). 53: 103-104, 2009.
  37. Goto K, Watashi K, Inoue D, Hijikata M, Shimotohno K. Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor. Cancer Sci. 100(10): 1943-1950, 2009
  38. Murakami Y, Aly HH, Tajima A, Inoue I, Shimotohno K. Regulation of the hepatitis C virus genome replication by miR-199a(*). J Hepatol. 50(3): 453-460, 2009
  39. Aly HH, Shimotohno K, Hijikata M.3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV. Biochem Biophys Res Commun. 379(2): 330-334, 2009.
  40. Zhang J, Yamada O, Kawagishi K, Araki H, Yamaoka S, Hattori T, Shimotohno K. Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300. Virology. 379(2): 306-313, 2008
  41. Ikejiri M, Ohshima T, Fukushima A, Shimotohno K, Maruyama T. Synthesis and evalua tion of 5′-modified 2′-deoxyadenosine analogues as anti-hepatitis C virus agents. Bioorg Med Chem Lett. 18(16): 4638-4641, 2008
  42. Noguchi T, Otsubaki T, Ando I, Ogura N, Ikeda S, Shimotohno K. Isolation and gene analysis of interferon alpha-resistant cell clones of the hepatitis C virus subgenome. Virology. 375(2): 424-432, 2008
  43. Nakamura M, Saito H, Ikeda M, Tada S, Kumagai N, Kato N, Shimotohno K, Hibi T. Possible molecular mechanism of the relationship between NS5B polymorphisms and early clearance of hepatitis C virus during interferon plus ribavirin treatment. J Med Virol. 80(4): 632-639, 2008
  44. Isono O, Ohshima T, Saeki Y, Matsumoto J, Hijikata M, Tanaka K, Shimotohno K. Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination. J Biol Chem. 283(49): 34273-34282, 2008.
  45. Aly HH, Watashi K, Hijikata M, Kaneko H, Takada Y, Egawa H, Uemoto S, Shimotohno K. Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes. J Hepatol. 46(1): 26-36, 2007.
  46. Zhang J, Yamada O, Yoshida H, Sakamoto T, Araki H, Shimotohno K. Helper virus-independent trans-replication of hepatitis C virus-derived minigenome. Biochem Biophys Res Commun. 352(1): 170-176, 2007
  47. Takao Y, Yamada A, Yutani S, Takedatsu H, Ono T, Etoh K, Wang Y, Suzuki S, Ide T, Shimotohno K, Sata M, Itoh K. Identification of new immunogenic peptides in conserved regions of hepatitis C virus (HCV) 1b with the potentiality to generate cytotoxic T lymphocytes in HCV1b(+) HLA-A24(+) patients. Hepatol Res. 2007 37(3): 186-195, 2007
  48. Watashi K, Shimotohno K.Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti-hepatitis C virus strategy. Rev Med Virol. 17: 245-252, 2007
  49. El-Farrash MA, Aly HH, Watashi K, Hijikata M, Egawa H, Shimotohno K. In vitro infection of immortalized primary hepatocytes by HCV genotype 4a and inhibition of virus replication by cyclosporin. Microbiol Immunol. 2007;51(1): 127-133, 2007
  50. Ishida T, Iwai A, Hijikata M, Shimotohno K. The expression of phosphatidic acid phosphatase 2a, which hydrolyzes lipids to generate diacylglycerol, is regulated by p73, a member of the p53 family. Biochem Biophys Res Commun. 353(1): 74-79, 2007
  51. Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T and Shimotohno K., Negative regulation of the RIG-I signaling by the novel ubiquitin ligase RNF125. Proc. Natl. Acd. Sci. USA 104: 7500-7505, 2007
  52. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K. The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol. 9(9): 1089-1097, 2007