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International Research Center for Infectious Diseases Department of Special Pathogens 高病原性感染症研究部門 ／■修校了／１－３４４／本文２／Ａ１３４４ＡＡ 2017.04.20 17.01.31 Page 1 125 International Research Center for Infectious Diseases Department of Special Pathogens 高病原性感染症研究部門 Professor Chieko Kai, D.V.M., Ph.D. 教授（兼） 農学博士 甲 斐 知恵子 Professor Yoshihiro Kawaoka, D.V.M., Ph.D. 教授（兼） 獣医学博士 河岡義裕 Highly pathogenic viral agents causing emerging infectious diseases are of con- cern not only to public health but also as possible biological weapons. The ulti- mate goal of our research is to unlock the secrets of the pathogenicity of such vi- ruses in humans and to develop effective vaccines and antiviral compounds against these pathogens. We have been investigating the molecular basis of the replication cycle and extreme virulence of special pathogens, using Ebola, influ- enza, and Nipa viruses as models. Region of Nipah virus C protein responsible for Arafa AS1, Yamada S, Imai M, Watanabe T, shuttling between the cytoplasm and nucleus. Yamayoshi S, Iwatsuki-Horimoto K, Kiso M, Sakai-Tagawa Y, Ito M, Imamura T, Nakajima Horie, R., Yoneda, M., Uchida, S., Sato, H. and N2, Takahashi K2, Zhao D, Oishi K, Yasuhara A, Kai, C. Macken CA3, Zhong G4, Hanson AP4, Fan S4,Ping J4, Hatta M4,LopesTJ4, Suzuki Y5, El-Husseiny Nipah virus (NiV) causes severe encephalitis in M1, Selim A1, Hagag N1, Soliman M6,NeumannG4, humans, with high mortality. NiV nonstructural C Hasegawa H2, Kawaoka Y.: 1National Laboratory protein (NiV-C) is essential for its pathogenicity, for Veterinary Quality Control on Poultry Produc- but its functions are unclear. In this study, we fo- tion, Animal Health Research Institute, Dokki, cused on NiV-C trafficking in cells and found that Giza, Egypt. 2Department of Pathology, National it localizes predominantly in the cytoplasm but Institute of Infectious Diseases, Sinjuku-ku, Tokyo partly in the nucleus. An analysis of NiV-C mu- 162-8640, Japan. 3Bioinformatics Institute, The tants showed that amino acids 2, 21-24 and 110-139 University of Auckland, Auckland 1142, New Zea- of NiV-C are important for its localization in the land. 4Influenza Research Institute, Department of cytoplasm. Inhibitor treatment indicates that the Pathobiological Sciences, School of Veterinary nuclear export determinant is not a classical CRM1- Medicine, University of Wisconsin-Madison, Madi- dependent nuclear export signal. We also deter- son, WI 53711, USA. 5College of Life and Health mined that amino acids 60-75 and 72-75 were im- Sciences, Chubu University, Aichi 487-8501, Ja- portant for nuclear localization of NiV-C. Further- pan. 6General Organization for Veterinary Serv- more, NiV-C mutants that had lost their capacity ices, Dokki, Giza, Egypt. for nuclear localization inhibited the interferon (IFN) response more strongly than complete NiV-C. Highly pathogenic avian influenza (HPAI) vi- These results indicate that the IFN-antagonist activ- ruses of the H5N1 subtype are enzootic in poultry ity of NiV-C occurs in the cytoplasm. populations in different parts of the world, and have caused numerous human infections in recent Risk assessment of recent Egyptian H5N1 influ- years, particularly in Egypt. However, no sustained enza viruses human-to-human transmission of these viruses has ／■修校了／１－３４４／本文２／Ａ１３４４ＡＡ 2017.04.20 17.01.31 Page 2 126 yet been reported. We tested nine naturally occur- in three additional transmission experiments in fer- ring Egyptian H5N1 viruses (isolated in 2014-2015) rets. Currently, we do not know if the efficiency of in ferrets and found that three of them transmitted transmission is very low or if subtle differences in via respiratory droplets, causing a fatal infection in experimental parameters contributed to these incon- one of the exposed animals. All isolates were sensi- sistent results. Nonetheless, our findings heighten tive to neuraminidase inhibitors. However, these vi- concern regarding the pandemic potential of recent ruses were not transmitted via respiratory droplets Egyptian H5N1 influenza viruses. Publications Shoji K, Yoneda M, Fujiyuki T, Amagai Y, Tanaka viruses. Proc Natl Acad Sci USA 113: E8396-E A,MatsudaAOgiharaK,NayaY,IkedaF,Ma- 8305, 2016. tsuda H, Sato H, and Kai C. Development of new Arafa A-S, Yamada S, Imai M, Watanabe T, therapy for canine mammary cancer with recom- Yamayoshi S, Iwatsuki-Horimoto K, Kiso M, binant measles virus. Molecular Therapy - Onco- Sakai-Tagawa Y, Ito M, Imamura T, Nakajima N, lytics 3: 15022, 2016 Takahashi K, Zhao D, Oishi K, Yasuhara A, Amagai Y, Fujiyuki T, Yoneda M, Shoji K, Fu- MackenC,ZhongG,HansonA,FanS,PingJ, rukawa Y, Sato H, Kai C. Oncolytic Activity of a Hatta M, Lopes T, Suzuki Y, El-Husseiny M, Recombinant Measles Virus, Blind to Signaling Selim A, Hagag N, Soliman M, Neumann G, Lymphocyte Activation Molecule, Against Col- Hasegawa H, Kawaoka Y. Risk assessment of re- orectal Cancer Cells. Sci Rep 6: 24572, 2016 cent Egyptian H5N1 influenza viruses. Sci Rep 6: Uchida, S., Sato, H., Yoneda, M. and Kai, C. Eu- 38388, 2016. karyotic elongation factor 1-beta interacts with Miyauchi K, Sugimoto-Ishige A, Harada Y, Adachi the 5′untranslated region of M in Nipah virus to Y, Usami Y, Kaji T, Inoue K, Hasegawa H, promote mRNA translation. Arch Virol 161(9): Watanabe T, Hijikata A, Fukuyama S, Maemura 2361-8, 2016 T, Okada-Hatakeyama M, Ohara O, Kawaoka Y, Horie R., Uchida S., Sato H., Kai C. and Yoneda M. TakahashiY,TakemoriT,KuboM.Protective Region of Nipah virus C protein responsible for neutralizing influenza antibody response in the shuttling between the cytoplasm and nucleus. Vi- absence of T follicular helper cells. Nat Immunol rology 497: 294-304, 2016 17: 1447-1458, 2016. Takenaka A., Sato H., Ikeda F., Yoneda M., Kai C. Sarawar S, Hatta Y, Watanabe S, Dias P, Neumann Infectious Progression of Canine Distemper Virus G, Kawaoka Y, Bilsel P. M2SR, a novel live single in Circulating Cerebrospinal Fluid to the Central replication influenza virus vaccine, provides ef- Nervous System. J Virol 90(20): 9285-9292, 2016 fective heterosubtypic protection in mice. Vaccine Awano M., Fujiyuki T., Shoji K., Amagai Y., Mu- 34: 5090-5098, 2016. rakami, Y., Furukawa, Y., Sato, H., Yoneda, M. Nakatsu S, Sagara H, Sakai-Tagawa Y, Sugaya N, and Kai, C. Measles virus selectively blind to Noda T, Kawaoka Y. Complete and Incomplete SLAM has oncolytic efficacy against nectin-4-ex- Genome Packaging of Influenza A and B Viruses. pressing pancreatic cancer cells. Cancer Science MBio 7: e01248-16, 2016. 07(11): 1647-1652, 2016 Chasman D, Walters KB, Lopes TJ, Eisfeld AJ, Doi T., Kwon H-J., Honda T., Sato H., Yoneda M., Kawaoka Y, Roy S. Integrating Transcriptomic Kai C. Measles virus induced persistent infection and Proteomic Data Using Predictive Regulatory by autoregulation of viral replication. Sci Rep 6: Network Models of Host Response to Pathogens. 37163, 2016. PLoS Comput Biol 12: e1005013, 2016. Iwatsuki-Horimoto K, Nakajima N, Shibata M, TakashitaE,EjimaM,OgawaR,FujisakiS,Neu- Takahashi K, Sato Y, Kiso M, Yamayoshi S, Ito mann G, Furuta Y, Kawaoka Y, Tashiro M, M, Enya S, Otake M, Kangawa A, Lopes T, Ito H, Odagiri T. Antiviral susceptibility of influenza vi- Hasegawa H, Kawaoka Y. Microminipigs as an ruses isolated from patients pre- and post-ad- animal model for influenza A virus infection. J ministration of favipiravir. Antiviral Res 132: 170- Virol (in press). 177, 2016. Gasper DJ, Neldner B, Plisch EH, Rustom H, Car- Westhoff Smith D, Hill-Batorski L, N'jai A, Eisfeld row E, Imai H, Kawaoka Y, Suresh M. Effective AJ, Neumann G, Halfmann P, Kawaoka Y. Ebola respiratory CD8 T-cell immunity to influenza vi- Virus Stability Under Hospital and Environ- rus induced by intranasal carbomer-lecithin-adju- mental Conditions. J Infect Dis 214: S142-144, vanted non-replicating vaccines. PLoS Pathog 12: 2016. e1006064, 2016. HsinKY,MatsuokaY,AsaiY,KamiyoshiK, Ping J, Lopes TJ, Neumann G, Kawaoka Y. Devel- Watanabe T, Kawaoka Y, Kitano H. systemsDock: opment of high-yield influenza B virus vaccine a web server for network pharmacology-based ／■修校了／１－３４４／本文２／Ａ１３４４ＡＡ 2017.04.20 17.01.31 Page 3 127 prediction and analysis. Nucleic Acids Res 44: W Friedrich TC. Selective bottlenecks shape evolu- 507-513, 2016. tionary pathways taken during mammalian adap- Li C, Hatta M, Burke DF, Ping J, Zhang Y, Ozawa tation of a 1918-like avian influenza virus. Cell M, Taft AS, Das SC, Hanson AP, Song J, Imai M, Host Microbe 19: 169-180, 2016. Wilker PR, Watanabe T, Watanabe S, Ito M, Iwa- Fujimoto Y, Ito H, Ono E, Kawaoka Y, Ito T. The tsuki-Horimoto K, Russell CA, James SL, Skepner low-pH resistance of neuraminidase is essential E, Maher EA, Neumann G, Klimov A, Kelso A, for the replication of influenza A virus in duck McCauley J, Wang D, Shu Y, OdagiriT, Tashiro intestine following infection via the rral route. J M, Xu X, Wentworth DE, Katz JM, Cox NJ, Smith Virol 90: 4127-4132, 2016. DJ, Kawaoka Y. Selection of antigenically ad- Katsura H, Fukuyama S, Watanabe S, Ozawa M, vanced variants of seasonal influenza viruses. Neumann G, Kawaoka Y. Amino acid changes in Nat Microbiol 1: 16058, 2016. PB2andHAaffectthegrowthofarecombinant Ando T, Yamayoshi S, Tomita Y, Watanabe S, influenza virus expressing a fluorescent reporter Watanabe T, Kawaoka Y. The host protein CLUH protein. Sci Rep 6: 19933, 2016. participates in the subnuclear transport of influ- Niu Z, Chasman D, Eisfeld AJ, Kawaoka Y, Roy S. enza virus ribonucleoprotein complexes. Nat Mi- Multi-task consensus clustering of genome-wide crobiol 1: 16062, 2016. transcriptomes from related biological conditions. Tisoncik-Go J, Gasper DJ, Kyle JE, Eisfeld AJ, Selin- Bioinformatics 32: 1509-1517, 2016. ger C, Hatta M, Morrison J, Korth MJ, Zink EM, Pécheur EI, Borisevich V, Halfmann P, Morrey JD, Kim YM, Schepmoes AA, Nicora CD, Purvine Smee DF, Prichard M, Mire CE,?Kawaoka Y, SO, Weitz KK, Peng X, Green RR, Tilton SC, Geisbert TW, Polyak SJ.
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