21

Department of Microbiology and Immunology

Division of Molecular Virology
ウイルス病態制御分野
Professor
Associate Professor
Assistant Professor
Assistant Professor

Yasushi Kawaguchi, D.V.M., Ph.D.
Akihisa Kato, Ph.D.
Naoto Koyanagi, Ph.D.
Yuhei Maruzuru, Ph.D.

教 授
准教授
助 教
助 教

博士（獣医学）
博士（医学）
博士（生命科学）
博士（生命科学）

川加
小丸

口藤栁
鶴哲直雄

寧久人平

In our laboratory, we are promoting strategic fundamental research aimed atdeveloping a novel method of viral infection control by elucidating the mechanism
underlying viral proliferation/pathology. Moreover, using viruses as a biologicalprobe, we are also challenging next-generation virology to reconsider viruses as ahomeostasis factor and explore their significance, in addition to unraveling cells
and physiological control mechanisms that cannot be elucidated by research on
normal human hosts.

1.  Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence
Ayano Fukui, Yuhei Maruzuru, Shiho Ohno1, Moeka Nobe, Shuji Iwata, Kosuke Takeshima, Naoto
Koyanagi, Akihisa Kato, Shinobu Kitazume2, Yoshiki Yamaguchi1, Yasushi Kawaguchi: 1Division ofStructural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical andPharmaceutical University, Miyagi 2Department ofClinical Laboratory Sciences, School of HealthSciences, Fukushima Medical University, Fukushima
Identification of the mechanisms of viral evasion
from human antibodies is crucial both for understanding viral pathogenesis and for designing effective vaccines. Here we show in cell cultures that anN-glycan shield on the herpes simplex virus 1 (HSV1) envelope glycoprotein B (gB) mediated evasion
from neutralization and antibody-dependent cellularcytotoxicity due to pooled γ-globulins derived fromhuman blood. We also demonstrated that the presence of human γ-globulins in mice and immunity to
HSV-1 induced by viral infection in mice significantly

reduced replication in their eyes of a mutant virus
lacking the glycosylation site but had little effect on
the replication of its repaired virus. These results suggest that an N-glycan shield on a specific site of HSV1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced byviral infection in vivo. Notably, we also found that anN-glycan shield on a specific site of HSV-1 gB was significant for HSV-1 neurovirulence and replication in
the central nervous system of naïve mice. Thus, wehave identified a critical N-glycan shield on HSV-1 gB
that has dual impacts, namely evasion from humanantibodies in vivo and viral neurovirulence.
2.  Establishment of a system to quantify wildtype herpes simplex virus-induced cell-cell fusion reveals a role of N-glycosylation of HSV-1
envelope glycoprotein B in cell-cell fusion
Ayano Fukui, Yuhei Maruzuru, Kosuke Takeshima,
Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
Wild-type herpes simplex virus (HSV) strains infrequently mediate cell-cell fusion in cell cultures andbarely induce large multinucleated cells. In this study,
we established a system to quantify infrequent cell-22cell fusion induced by wild-type HSV strains. The established system clarified that the HSV-1 envelope
glycoprotein B and its N-glycosylation at asparagine
at position 141 were required for efficient cell-cell fu-sion. This study provides a link between cell-cell fusion induced by wild-type HSV-1 and viral pathogenesis in vivo.

Publications
Fukui, A., Maruzuru, Y., Ohno, S., Nobe, M., Iwata, S.,
Takeshima, K., Koyanagi, N., Kato, A., Kitazume,S., Yamaguchi, Y., Kawaguchi, Y. Dual impacts of aglycan shield on the envelope glycoprotein B ofHSV-1: evasion from human antibodies in vivo andneurovirulence. mBio 14: e00992-23, 2023.
Fukui, A., Maruzuru, Y., Takeshima, K., Koyanagi, N.,Kato, A., Kawaguchi, Y. Establishment of a system
to quantify wild-type herpes simplex virus-induced cell-cell fusion reveals a role of N-glycosylation of HSV-1 envelope glycoprotein B in cell-cellfusion. Microbiol. Immunol. 67: 114-119, 2023.
Kuchitsu, Y., Mukai, K., Uematsu, R., Takaada, Y.,
Shinojima, A., Shindo, R., Shoji, T., Hamano, S.,
Ogawa, E., Sato, R., Miyake, K., Kato, A., Kawaguchi, Y., Nishitani-Isa, M., Izawa, K., Nishikomori,R., Yasumi, T., Suzuki, T., Dohmae, N., Uemura, T.,
Barber, G. N., Arai, H., Waguri, S., Taguchi, T.
STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originatingfrom recycling endosomes. Nat. Cell Biol. 25: 453466, 2023.
Duncan, J. K. S., Xu, D., Licursi, M., Joyce, M. A., Saffran, H. A., Liu, K., Gohda, J., Tyrrell, D. L., Kawaguchi, Y., Hirasawa, K. Interferon regulatory factor
3 mediates effective antiviral responses to humancoronavirus 229E and OC43 infection. Front. Immunol. 14: 930086, 2023.
Hassan, A. H. E., El-Sayed, S. M., Yamamoto, M.,
Gohda, J., Matsumoto, T., Shirouzu, M., Inoue, J.,Kawaguchi, Y., Mansour, R. M. A., Anvari, A., Farahat, A. A. In silico and in vitro evaluation of someamidine derivatives as hit compounds towards development of inhibitors against coronavirus diseases. Viruses 15: 1171, 2023.
Nagai, K., Muto, Y., Miura, S., Takahashi, K., Naruse,Y., Hiruta, R., Hashimoto, Y., Uzuki, M., Haga, Y.,Fujii, R., Ueda, K., Kawaguchi, Y., Fujii, M., Kitazume, S. Brain-specific glycosylation enzyme GnTIX maintains levels of protein tyrosine phosphatase
receptor PTPRZ, thereby mediating glioma growth
PTPRZ glycosylation regulates glioma growth. J.
Biol. Chem. 299: 105128, 2023.
Takahashi, K., Kanekiyo, K., Sakuda, K., Muto, Y., Iguchi, M., Matsuda, N., Hashimoto, Y., Kanai, K.,
Ogawa, H., Hirase, H., Kakita, A., Bizen, N., Takebayashi, H., Kawaguchi, Y., Uzuki, M., Kitazume, S.
Brain-specific glycosylation of protein tyrosine
phosphatase receptor type Z (PTPRZ) marks a demyelination-associated astrocyte subtype. J. Neurochem. 166: 547-559, 2023.