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Toru
Takimoto
Assistant Professor of Microbiology & Immunology Primary Academic Appointment: GEBS
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University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Medical Center Room 2-9804 (Lab) Room 2-9607 (Office) Phone: (585) 273-2856 Fax: (585) 473-9573 E-Mail: toru_takimoto@ urmc.rochester.edu |
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- Research Focus
- Molecular Mechanisms of Paramyxovirus Infection, Replication and Assembly
- Research Overview
- Paramyxoviruses include various important human and animal pathogens, such as parainfluenza, respiratory syncytial, and measles viruses. In my laboratory, we are examining the molecular mechanisms of paramyxovirus infection, replication, and assembly to develop applications in the prevention or remedy of paramyxovirus disease. We are studying 1) the functions of viral envelope glycoproteins to initiate infection (attachment and penetration by fusion), 2) protein-protein interaction between viral polymerase proteins and host cell proteins required for the replication and transcription of viral genome, and 3) mechanism of viral assembly and budding. We use reverse genetics technique to produce mutant Sendai virus (SV) from cDNA, which allows us to analyze the functions of viral proteins in the life cycle both in vitro and in vivo.
- A second major project is to determine the cellular factors that restrict the host range of paramyxoviruses. We use closely related human parainfluenza virus type 1 (hPIV1) and SV (murine parainfluenza virus type 1). In spite of their similarity in structure and amino acid sequences, the host range of these viruses is totally different. The hPIV1 infects and causes respiratory disease among humans but not in mice. Likewise, SV is a lethal pathogen in mice, while no infection was reported among humans. Our data suggests that the viral ability to antagonize interferon (IFN) activity is species-specific and plays a major role on viral pathogenicity in its natural host. In my laboratory, we continue to characterize the mechanisms which contribute to the virus¹ ability to antagonize the antiviral action(s) of IFN in its natural host species.
- Recent Publications
- Brown SA, Hurwitz JL, Zirkel A, Surman S, Takimoto T, Alymova I, Coleclough C, Portner A, Doherty PC, Slobod KS "A recombinant Sendai virus is controlled by CD4+ effector T cells responding to a secreted HIV-1 envelope glycoprotein." J Virol. 2007 Nov;81(22):12535-42
- Bousse T, Takimoto T. "Mutation at residue 523 creates a second receptor binding site on human parainfluenza virus type 1 hemagglutinin-neuraminidase protein." J Virol. 2006 Sep;80(18):9009-16
- Bousse T, Chambers RL, Scroggs RA, Portner A, Takimoto T. "Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment." Virus Res. 2006 May 2;
- Takimoto T, Hurwitz J. L., Zhan X, Krishnamurthy S, Prouser C, Brown, B, Coleclough C, Boyd K, Scroggs R. A, Portner A, Slobod, K. S. "Recombinant sendai virus as a novel vaccine candidate for respiratory syncytial virus." Viral Immunol 18(2): 255-66, 2005
- Alymova IV, Portner A, Takimoto T, Boyd KL, Babu YS, McCullers JA. The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. Antimicrob Agents Chemother. 49:398-405, 2005.
- Takimoto T, Portner A. Molecular mechanism of paramyxovirus budding. Virus Res. 106:133-45, 2004.
- Bousse TL, Taylor G, Krishnamurthy S, Portner A, Samal SK, Takimoto T. Biological significance of the second receptor binding site of Newcastle disease virus hemagglutinin-neuraminidase protein. J Virol. 78:13351-5, 2004.
- Takimoto T, Hurwitz JL, Coleclough C, Prouser C, Krishnamurthy S, Zhan X, Boyd K, Scroggs RA, Brown B, Nagai Y, Portner A, Slobod KS. Recombinant Sendai virus expressing the G glycoprotein of respiratory syncytial virus (RSV) elicits immune protection against RSV. J Virol. 78:6043-7, 2004.
- Alymova IV, Taylor G, Takimoto T, Lin TH, Chand P, Babu YS, Li C, Xiong X, Portner A. Efficacy of novel hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo. Antimicrob Agents Chemother. 48:1495-502, 2004.
- Zaitsev V, von Itzstein M, Groves D, Kiefel M, Takimoto T, Portner A, Taylor G. Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. J Virol. 78:3733-41, 2004.
- Takimoto T, Taylor GL, Connaris HC, Crennell SJ, Portner A. Role of the hemagglutinin-neuraminidase protein in the mechanism of paramyxovirus-cell membrane fusion. J Virol. 76:13028-33, 2002.
- Bousse T, Matrosovich T, Portner A, Kato A, Nagai Y, Takimoto T. The long noncoding region of the human parainfluenza virus type 1 f gene contributes to the read-through transcription at the m-f gene junction. J Virol. 76:8244-51, 2002.
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