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Toru Takimoto

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester NY 14642
 
 Overview
RESEARCH ACTIVITIES

Research project in progress
The major areas of research in my laboratory are as follows:
Molecular mechanism of paramyxovirus assembly: Efficient assembly and release of progeny virions from infected cells are major determinants of viral pathogenicity. Molecular mechanism of paramyxovirus assembly is not well understood. We are characterizing the trafficking of viral nucleocapsid to the site of assembly at the plasma membrane to understand the cellular machinery viruses utilize for assembly of progeny virions. URSMD Collaborators = Brian Ward, Minsoo Kim.

Assembly of Influenza A viruses: Influenza viruses replicate and form nucleocapsid core in nuclei of infected cells. The progeny nucleocapsid cores are then transported to the plasma membrane budding sites. This study analyzes cellular and viral protein interactions required for the nuclear export of nucleocapsid and budding of progeny virions. URSMD Collaborators = Brian Ward

Role of Influenza Virus Polymerase in Host Adaptation: We participate in the virology research team of the New York Influenza Center of Excellence (NYICE), which is part of the NIH Centers of Excellence for Influenza Research and Surveillance (CEIRS) network. Our focus is on the influenza virus RNA polymerase, and understanding how it contributes to host adaptation. We characterize the polymerase activities of avian and human strains, and identify residues and subunits of the polymerase complex important for the enhanced activity in mammalian hosts in vitro and in vivo. URSMD Collaborators = David Topham, John Treanor, Steve Dewhurst, Baek Kim.

 
 Selected Publications
List All   |   Timeline
  1. Bialas KM, Bussey KA, Stone RL, Takimoto T. Specific nucleoprotein residues affect influenza virus morphology. J Virol. 2014 Feb; 88(4):2227-34.
    View in: PubMed
  2. Kobayashi H, Iwatsuki-Horimoto K, Kiso M, Uraki R, Ichiko Y, Takimoto T, Kawaoka Y. A replication-incompetent influenza virus bearing the HN glycoprotein of human parainfluenza virus as a bivalent vaccine. Vaccine. 2013 Dec 16; 31(52):6239-46.
    View in: PubMed
  3. Stone R, Takimoto T. Critical role of the fusion protein cytoplasmic tail sequence in parainfluenza virus assembly. PLoS One. 2013; 8(4):e61281.
    View in: PubMed
  4. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz JM, Kiselev OI, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Transmission studies resume for avian flu. Science. 2013 Feb 1; 339(6119):520-1.
    View in: PubMed
  5. Desmet EA, Bussey KA, Stone R, Takimoto T. Identification of the N-Terminal Domain of the Influenza Virus PA Responsible for the Suppression of Host Protein Synthesis. J Virol. 2013 Mar; 87(6):3108-18.
    View in: PubMed
  6. Bialas KM, Desmet EA, Takimoto T. Specific Residues in the 2009 H1N1 Swine-Origin Influenza Matrix Protein Influence Virion Morphology and Efficiency of Viral Spread In Vitro. PLoS One. 2012; 7(11):e50595.
    View in: PubMed
  7. Noronha JM, Liu M, Squires RB, Pickett BE, Hale BG, Air GM, Galloway SE, Takimoto T, Schmolke M, Hunt V, Klem E, García-Sastre A, McGee M, Scheuermann RH. Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction. J Virol. 2012 May; 86(10):5857-66.
    View in: PubMed
  8. MacDonald LA, Aggarwal S, Bussey KA, Desmet EA, Kim B, Takimoto T. Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies. Virology. 2012 Apr 25; 426(1):51-9.
    View in: PubMed
  9. Fouchier RA, García-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Mettenleiter TC, Osterhaus AD, Palese P, Peiris JS, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RG. Pause on avian flu transmission research. Science. 2012 Jan 27; 335(6067):400-1.
    View in: PubMed
  10. Jones BG, Sealy RE, Rudraraju R, Traina-Dorge VL, Finneyfrock B, Cook A, Takimoto T, Portner A, Hurwitz JL. Sendai virus-based RSV vaccine protects African green monkeys from RSV infection. Vaccine. 2012 Jan 20; 30(5):959-68.
    View in: PubMed
  11. Aggarwal S, Dewhurst S, Takimoto T, Kim B. Biochemical impact of the host adaptation-associated PB2 E627K mutation on the temperature-dependent RNA synthesis kinetics of influenza A virus polymerase complex. J Biol Chem. 2011 Oct 7; 286(40):34504-13.
    View in: PubMed
  12. Bussey KA, Desmet EA, Mattiacio JL, Hamilton A, Bradel-Tretheway B, Bussey HE, Kim B, Dewhurst S, Takimoto T. PA residues in the 2009 H1N1 pandemic influenza virus enhance avian influenza virus polymerase activity in mammalian cells. J Virol. 2011 Jul; 85(14):7020-8.
    View in: PubMed
  13. Noble E, Mathews DH, Chen JL, Turner DH, Takimoto T, Kim B. Biophysical analysis of influenza A virus RNA promoter at physiological temperatures. J Biol Chem. 2011 Jul 1; 286(26):22965-70.
    View in: PubMed
  14. Fukushima K, Takahashi T, Takaguchi M, Ueyama H, Ito S, Kurebayashi Y, Kawanishi T, McKimm-Breschkin JL, Takimoto T, Minami A, Suzuki T. Plaque formation assay for human parainfluenza virus type 1. Biol Pharm Bull. 2011; 34(7):996-1000.
    View in: PubMed
  15. Guo H, Santiago F, Lambert K, Takimoto T, Topham DJ. T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model. J Virol. 2011 Jan; 85(1):448-55.
    View in: PubMed
  16. Chambers R, Takimoto T. Trafficking of Sendai virus nucleocapsids is mediated by intracellular vesicles. PLoS One. 2010; 5(6):e10994.
    View in: PubMed
  17. Aggarwal S, Bradel-Tretheway B, Takimoto T, Dewhurst S, Kim B. Biochemical characterization of enzyme fidelity of influenza A virus RNA polymerase complex. PLoS One. 2010; 5(4):e10372.
    View in: PubMed
  18. Desmet EA, Hollenbaugh JA, Sime PJ, Wright TW, Topham DJ, Sant AJ, Takimoto T, Dewhurst S, Maggirwar SB. Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells. Virology. 2010 May 10; 400(2):224-32.
    View in: PubMed
  19. Bussey KA, Bousse TL, Desmet EA, Kim B, Takimoto T. PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells. J Virol. 2010 May; 84(9):4395-406.
    View in: PubMed
  20. Chambers R, Takimoto T. Antagonism of innate immunity by paramyxovirus accessory proteins. Viruses. 2009 Dec; 1(3):574-93.
    View in: PubMed
  21. Chambers R, Takimoto T. Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products. J Gen Virol. 2009 Aug; 90(Pt 8):1906-15.
    View in: PubMed
  22. Bradel-Tretheway BG, Kelley Z, Chakraborty-Sett S, Takimoto T, Kim B, Dewhurst S. The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit. J Gen Virol. 2008 Dec; 89(Pt 12):2923-32.
    View in: PubMed
  23. Zhan X, Slobod KS, Krishnamurthy S, Luque LE, Takimoto T, Jones B, Surman S, Russell CJ, Portner A, Hurwitz JL. Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1, hPIV-3 and RSV infections. Vaccine. 2008 Jun 25; 26(27-28):3480-8.
    View in: PubMed
  24. Zhan X, Hurwitz JL, Krishnamurthy S, Takimoto T, Boyd K, Scroggs RA, Surman S, Portner A, Slobod KS. Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B. Vaccine. 2007 Dec 17; 25(52):8782-93.
    View in: PubMed
  25. 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 human immunodeficiency virus type 1 envelope glycoprotein. J Virol. 2007 Nov; 81(22):12535-42.
    View in: PubMed
  26. 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.
    View in: PubMed
  27. Krishnamurthy S, Takimoto T, Scroggs RA, Portner A. Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines. J Virol. 2006 Jun; 80(11):5145-55.
    View in: PubMed
  28. 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 Oct; 121(1):23-32.
    View in: PubMed
  29. 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. 2005 Jan; 49(1):398-405.
    View in: PubMed
  30. Takimoto T, Hurwitz JL, Zhan X, Krishnamurthy S, Prouser C, Brown B, Coleclough C, Boyd K, Scroggs RA, Portner A, Slobod KS. Recombinant Sendai virus as a novel vaccine candidate for respiratory syncytial virus. Viral Immunol. 2005; 18(2):255-66.
    View in: PubMed
  31. Takimoto T, Portner A. Molecular mechanism of paramyxovirus budding. Virus Res. 2004 Dec; 106(2):133-45.
    View in: PubMed
  32. 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. 2004 Dec; 78(23):13351-5.
    View in: PubMed
  33. 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. 2004 Jun; 78(11):6043-7.
    View in: PubMed
  34. 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. 2004 May; 48(5):1495-502.
    View in: PubMed
  35. 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. 2004 Apr; 78(7):3733-41.
    View in: PubMed
  36. 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. 2002 Dec; 76(24):13028-33.
    View in: PubMed
  37. 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. 2002 Aug; 76(16):8244-51.
    View in: PubMed
  38. Connaris H, Takimoto T, Russell R, Crennell S, Moustafa I, Portner A, Taylor G. Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: identification of key amino acids involved in cell binding, catalysis, and fusion. J Virol. 2002 Feb; 76(4):1816-24.
    View in: PubMed
  39. Takimoto T, Murti KG, Bousse T, Scroggs RA, Portner A. Role of matrix and fusion proteins in budding of Sendai virus. J Virol. 2001 Dec; 75(23):11384-91.
    View in: PubMed
  40. Bousse T, Takimoto T, Matrosovich T, Portner A. Two regions of the P protein are required to be active with the L protein for human parainfluenza virus type 1 RNA polymerase activity. Virology. 2001 May 10; 283(2):306-14.
    View in: PubMed
  41. Suzuki T, Portner A, Scroggs RA, Uchikawa M, Koyama N, Matsuo K, Suzuki Y, Takimoto T. Receptor specificities of human respiroviruses. J Virol. 2001 May; 75(10):4604-13.
    View in: PubMed
  42. Coronel EC, Takimoto T, Murti KG, Varich N, Portner A. Nucleocapsid incorporation into parainfluenza virus is regulated by specific interaction with matrix protein. J Virol. 2001 Feb; 75(3):1117-23.
    View in: PubMed
  43. Crennell S, Takimoto T, Portner A, Taylor G. Crystal structure of the multifunctional paramyxovirus hemagglutinin-neuraminidase. Nat Struct Biol. 2000 Nov; 7(11):1068-74.
    View in: PubMed
  44. Takimoto T, Bousse T, Portner A. Molecular cloning and expression of human parainfluenza virus type 1 L gene. Virus Res. 2000 Sep; 70(1-2):45-53.
    View in: PubMed
  45. Takimoto T, Taylor GL, Crennell SJ, Scroggs RA, Portner A. Crystallization of Newcastle disease virus hemagglutinin-neuraminidase glycoprotein. Virology. 2000 Apr 25; 270(1):208-14.
    View in: PubMed
  46. Chen Y, Takimoto T, Liu L, Surman S, Woodland DL. DNA vaccination as a tool to identify subdominant CD8 T cell epitopes. Vaccine. 1999 Nov 12; 18(7-8):720-7.
    View in: PubMed
  47. Coronel EC, Murti KG, Takimoto T, Portner A. Human parainfluenza virus type 1 matrix and nucleoprotein genes transiently expressed in mammalian cells induce the release of virus-like particles containing nucleocapsid-like structures. J Virol. 1999 Aug; 73(8):7035-8.
    View in: PubMed
  48. Takimoto T, Bousse T, Coronel EC, Scroggs RA, Portner A. Cytoplasmic domain of Sendai virus HN protein contains a specific sequence required for its incorporation into virions. J Virol. 1998 Dec; 72(12):9747-54.
    View in: PubMed
  49. Bousse T, Takimoto T, Murti KG, Portner A. Elevated expression of the human parainfluenza virus type 1 F gene downregulates HN expression. Virology. 1997 May 26; 232(1):44-52.
    View in: PubMed
  50. Bousse T, Takimoto T, Portner A. A single amino acid changes enhances the fusion promotion activity of human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein. Virology. 1995 Jun 1; 209(2):654-7.
    View in: PubMed
  51. Satoh K, Kimura K, Yoshida Y, Ota Y, Taniguchi Y, Kihira K, Kasano T, Takimoto T, Suzuki T, Seki M, et al. Relationship between Helicobacter pylori and atrophic gastritis. Eur J Gastroenterol Hepatol. 1994 Dec; 6 Suppl 1:S85-8.
    View in: PubMed
  52. Bousse T, Takimoto T, Gorman WL, Takahashi T, Portner A. Regions on the hemagglutinin-neuraminidase proteins of human parainfluenza virus type-1 and Sendai virus important for membrane fusion. Virology. 1994 Nov 1; 204(2):506-14.
    View in: PubMed
  53. Hyland L, Hou S, Coleclough C, Takimoto T, Doherty PC. Mice lacking CD8+ T cells develop greater numbers of IgA-producing cells in response to a respiratory virus infection. Virology. 1994 Oct; 204(1):234-41.
    View in: PubMed
  54. Takimoto T, Portner A. The human parainfluenza virus type-1 prototypic strain contains a heat-labile hemagglutinin-neuraminidase protein. Virus Res. 1994 Apr; 32(1):85-92.
    View in: PubMed
  55. Dave VP, Allan JE, Slobod KS, Smith FS, Ryan KW, Takimoto T, Power UF, Portner A, Hurwitz JL. Viral cross-reactivity and antigenic determinants recognized by human parainfluenza virus type 1-specific cytotoxic T-cells. Virology. 1994 Mar; 199(2):376-83.
    View in: PubMed
  56. Murti KG, Takimoto T, Laver WG, Portner A. Crystals of hemagglutinin-neuraminidase of parainfluenza virus contain triple-stranded helices. Proc Natl Acad Sci U S A. 1993 Feb 15; 90(4):1523-5.
    View in: PubMed
  57. Takimoto T, Laver WG, Murti KG, Portner A. Crystallization of biologically active hemagglutinin-neuraminidase glycoprotein dimers proteolytically cleaved from human parainfluenza virus type 1. J Virol. 1992 Dec; 66(12):7597-600.
    View in: PubMed
  58. Sato H, Takimoto T, Tanaka S, Tanaka J, Raab-Traub N. Concatameric replication of Epstein-Barr virus: structure of the termini in virus-producer and newly transformed cell lines. J Virol. 1990 Nov; 64(11):5295-300.
    View in: PubMed
  59. Sato H, Takimoto T, Tanaka S, Ogura H, Shiraishi K, Tanaka J. Cytopathic effects induced by Epstein-Barr virus replication in epithelial nasopharyngeal carcinoma hybrid cells. J Virol. 1989 Aug; 63(8):3555-9.
    View in: PubMed
  60. Takimoto T, Tanaka S, Ishikawa S, Masuda K, Umeda R. Further studies on growth characteristics of Epstein-Barr virus (EBV) genome-positive and -negative epithelial hybrid cell lines. Laryngoscope. 1989 Jul; 99(7 Pt 1):741-3.
    View in: PubMed
  61. Sato H, Takimoto T, Hatano M, Pagano JS, Raab-Traub N. Epstein-Barr virus with transforming and early antigen-inducing ability originating from nasopharyngeal carcinoma: mapping of the viral genome. J Gen Virol. 1989 Mar; 70 ( Pt 3):717-27.
    View in: PubMed
  62. Takimoto T, Sato H, Ogura H, Tanaka S, Umeda R. The difference in tumorigenicity between Epstein-Barr virus (EBV) genome-positive and genome-negative epithelial hybrid cell lines derived from the human nasopharynx. Laryngoscope. 1988 Dec; 98(12):1334-8.
    View in: PubMed
  63. Sato H, Takimoto T, Pagano JS, Raab-Traub N. Amplification of Epstein-Barr virus (EBV) DNA by superinfection with a strain of EBV derived from nasopharyngeal carcinoma. J Virol. 1988 Sep; 62(9):3288-94.
    View in: PubMed
  64. Ito T, Takimoto T, Yanagawa R. Presence of a variety of antigenic variants belonging to at least 4 different serovars in a population of Leptospira interrogans serovar hebdomadis. Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Jul; 269(1):15-25.
    View in: PubMed
  65. Takimoto T, Ono E, Ito T, Yanagawa R. Affinity constants of anti-leptospira monoclonal antibodies, numbers of antigenic determinants on leptospiras, and their influence on the microscopic agglutination test and ELISA. Microbiol Immunol. 1988; 32(8):775-84.
    View in: PubMed
  66. Takimoto T, Sato H, Ogura H, Glaser R. Rescue of a biologically active Epstein-Barr virus from nonproducer cells. Cancer Res. 1986 Apr; 46(4 Pt 2):2085-7.
    View in: PubMed
  67. Takimoto T, Morishita K, Umeda R, Ogura H, Hatano M. Infection of human epithelial cell lines by Epstein-Barr virus. Interaction between epithelial cell and B lymphocyte. ORL J Otorhinolaryngol Relat Spec. 1984; 46(4):195-201.
    View in: PubMed

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