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Department of Microbiology
Our main research interest is to understand cellular and molecular mechanisms of viral growth and virulence of the family Paramyxoviridae. This family is one of non-segment, negative-strand RNA viruses, and includes many well-known human and animal pathogens, such as human parainfluenza virus type (PIV) 1-4, measles virus, mumps virus, Sendai virus, Nipah virus, and RS virus. We have been studying PIV2, PIV5, SV41, and Sendai virus, using reverse genetics and other methods.
For viral replication, the ability to resist host defense mechanism is essential. Recent investigations demonstrate that the hPIV2 V protein plays a central role in the blockade of IFN system. We demonstrated that the V protein binds with TLR7, TLR9, and MDA-5, and these bindings suppress intracellular signaling downstream of these receptor activation and inhibit IFN induction. In addition, the V protein binds with STAT proteins, inducing degradation of STAT2 protein and blockade of the IFN signaling. The functions of the V protein in virus replication are not only the blockade of IFN system, but also the inhibitions of cell fusion, and virus genome replication.
To explore the mechanisms of viral growth, we are currently conducing the following projects.
- Identification of cellular proteins that interact with viral proteins.
- Functional studies of each viral protein.
- Molecular mechanisms of immune system inhibited by viral proteins.
- Development of highly efficient reverse genetics system for negative-strand RNA viruses.
These findings are of fundamental interest, and may also contribute to the future development of novel antiviral drugs and vaccines.
- Matsumoto Y, Ohta K, Goto H, Nishio M. Parainfluenza virus chimeric minireplicons reveal a novel regulatory element in the leader promoter. J Gen Virol. In press, 2016
- Ohta K, Goto H, Yumine N, Nishio M. Human parainfluenza virus type 2 V protein inhibits and antagonizes tetherin. J Gen Virol. In press, 2016
- Goto H, Ihira H, Morishita K, Tsuchiya M, Ohta K, Yumine N, Tsurudome M, Nishio M. Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2. Med Microbiol Immunol. In press, 2016
- Tsurudome M, Ito M, Ohtsuka J, Hara K, Komada H, Nishio M, Nosaka T. The fusion protein specificity of the parainfluenza virus hemagglutinin-neuraminidase protein is not solely defined by the primary structure of its stalk domain. J Viol. 89:12374-12387, 2015
- Matsumoto Y, Ohta K, Yumine N, Goto H, Nishio M. Identification of two essential aspartates for polymerase activity in parainfluenza virus L protein by a minireplicon system expressing secretory luciferase. Microbiol Immunol. 59:676-683, 2015
- Ito M, Kubota H, Takeuchi T, Qiao S, Tsurudome M, Tsumura H, Matsuda A, Nishio M, Ito Y. Pathogenesis of the influenza virus in diabetes model mice. BMRJ 9:1-7, 2015
- Kojima S, Honda T, Matsumoto Y, Tomonaga K. Heat stress is a potent stimulus for enhancing rescue efficiency of recombinant Borna disease virus. Microbiol Immunol. 58:636-642, 2014
- Ohtsuka J, Fukumura M, Tsurudome M, Hara K, Nishio M, Kawano M, Nosaka T. Vero/BC-F: an efficient packaging cell line stably expressing F protein to generate single round-infectious human parainfluenza virus type 2 vector. Gene Ther. 21:775-784, 2014
- Tsurudome M, Nakahashi M, Matsushima Y, Ito M, Nishio M, Kawano M, Komada H, Nosaka T. Full conversion of the hemagglutinin-neuraminidase specificity of the parainfluenza virus 5 fusion protein by replacement of 21 amino acids in its head region with those of the simian virus 41 fusion protein. J Virol. 87:8342-8350, 2013
- Kitagawa Y, Yamaguchi M, Zhou M, Nishio M, Itoh M, Gotoh B. Human parainfluenza virus type 2 V protein inhibits TRAF6-mediated ubiquitination of IRF7 to prevent TLR7- and TLR9-dependent interferon induction. J Virol. 87:7966-7976, 2013
- Masuda T, Ohta K, Mikami B, Kitabatake N, Tani F. Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change. Biochem. Biophys. Res. Commun. 419: 72-76, 2012
- Matsumoto Y, Hayashi Y, Omori H, Honda T, Daito T, Horie M, Ikuta K, Fujino K, Nakamura S, Schneider U, Chase G, Yoshimori T, Schwemmle M, Tomonaga K. Bornavirus closely associates and segregates with host chromosomes to ensure persistant intranuclear infection. Cell Host Microbe. 11:492-503, 2012
- Kitagawa Y, Yamaguchi M, Zhou M, Komatsu T, Nishio M, Sugiyama T, Takeuchi K, Itoh M, Gotoh B. A Tryptophan-rich motif in the human parainfluenza virus type 2 V protein is critical for the blockade of Toll-like receptor 7/9 dependent signaling. J. Virol. 85: 4604-4611, 2011
- Tsurudome M, Ito M, Nishio M, Nakahashi M, Kawano M, Komada H, Nosaka T, Ito Y. Identification of domains on the fusion (F) protein trimer that influence the hemagglutinin-neuraminidase specificity of the F protein in mediating cell-cell fusion. J. Virol. 85: 3153-3161, 2011
- Nishio M, Tsurudome M, Garcin D, Komada H, Ito M, Le Mercier P, Nosaka T, Kolakofsky D. Human parainfluenza virus type 2 L protein regions required for interaction with other viral proteins and mRNA capping. J. Virol. 85: 725-732, 2011
- Komada H, Kawano M, Uefuji A, Ito M, Tsurudome M, Hatakeyama E, Nakanishi M, Sakue S, Joh C, Suzumura E, Tamaki T, Tomioka T, Nishio M, Tsumura H, Uematsu J, Yamamoto H, O'Brien M, Bando H, Ito Y. Completion of the full-length genome sequence of human parainfluenza virus type 4A and 4B: Sequence analyses of the large protein genes, and gene start, intergenic and end sequences. Arch. Virol. 156: 161-166, 2011
- Schaap-Nutt A, D’Angelo C, Scull MA, Amaro-Carambot E, Nishio M, Pickles RJ, Collins PL, Murphy BR, Schmidt AC. Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates. Virology 397: 285-298, 2010