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Toru Takimoto, D.V.M., Ph.D.

Toru Takimoto, D.V.M., Ph.D.

Research Lab

About Me

Faculty Appointments

Associate Professor - Department of Microbiology and Immunology (SMD)

Credentials

Post-doctoral Training & Residency

Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 1990 - 1995

Education

PhD | Japan-Hokkaido University - Sapporo. Microbiology. 1994

DVM | Japan-Hokkaido University - Sapporo. Veterinary Medicine. 1989

MS | Japan-Hokkaido University - Sapporo. Microbiology. 1988

BS | Japan-Hokkaido University - Sapporo. Veterinary Medicine. 1986

Research

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 mec...
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.

Publications

Journal Articles

Host adaptive mutations in the 2009 H1N1 pandemic influenza A virus PA gene regulate translation efficiency of viral mRNAs via GRSF1.

Lutz M, Schmierer J, Takimoto T

Communications biology.. 2022 October 175 (1):1102. Epub 10/17/2022.

Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro.

Raymonda MH, Ciesla JH, Monaghan M, Leach J, Asantewaa G, Smorodintsev-Schiller LA, Lutz MM, Schafer XL, Takimoto T, Dewhurst S, Munger J, Harris IS

Virology.. 2021 November 27566 :60-68. Epub 11/27/2021.

Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells.

Kurebayashi Y, Bajimaya S, Watanabe M, Lim N, Lutz M, Dunagan M, Takimoto T

PLoS pathogens.. 2021 September 17 (9):e1009908. Epub 09/16/2021.

Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses.

Dunagan MM, Hardy K, Takimoto T

Vaccines.. 2021 June 109 (6)Epub 06/10/2021.

The Viral Polymerase Complex Mediates the Interaction of Viral Ribonucleoprotein Complexes with Recycling Endosomes during Sendai Virus Assembly.

Genoyer E, Kulej K, Hung CT, Thibault PA, Azarm K, Takimoto T, Garcia BA, Lee B, Lakdawala S, Weitzman MD, López CB

mBio.. 2020 August 2511 (4)Epub 08/25/2020.

Safety and immunogenicity of an intranasal sendai virus-based vaccine for human parainfluenza virus type I and respiratory syncytial virus (SeVRSV) in adults.

Scaggs Huang F, Bernstein DI, Slobod KS, Portner A, Takimoto T, Russell CJ, Meagher M, Jones BG, Sealy RE, Coleclough C, Branum K, Dickey M, Buschle K, McNeal M, Makowski M, Nakamura A, Hurwitz JL

Human vaccines & immunotherapeutics.. 2020 August 4 :1-6. Epub 08/04/2020.

Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses.

Lutz Iv MM, Dunagan MM, Kurebayashi Y, Takimoto T

Viruses.. 2020 March 2612 (4)Epub 03/26/2020.

Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity.

Chaimayo C, Dunagan M, Hayashi T, Santoso N, Takimoto T

PLoS pathogens.. 2018 November 14 (11):e1007465. Epub 11/29/2018.

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

Bajimaya S, Frankl T, Hayashi T, Takimoto T

Virology.. 2017 October 510 :234-241. Epub 07/25/2017.

A Sendai virus recombinant vaccine expressing a gene for truncated human metapneumovirus (hMPV) fusion protein protects cotton rats from hMPV challenge.

Russell CJ, Jones BG, Sealy RE, Surman SL, Mason JN, Hayden RT, Tripp RA, Takimoto T, Hurwitz JL

Virology.. 2017 September 509 :60-66. Epub 06/09/2017.

Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein.

Chaimayo C, Hayashi T, Underwood A, Hodges E, Takimoto T

Virology.. 2017 May 505 :23-32. Epub 02/17/2017.

Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses.

Bajimaya S, Hayashi T, Frankl T, Bryk P, Ward B, Takimoto T

Virology.. 2017 January 15501 :127-135. Epub 12/02/2016.

Rescue of Sendai Virus from Cloned cDNA.

Bajimaya S, Hayashi T, Takimoto T

Methods in molecular biology.. 2017 1602 :103-110. Epub 1900 01 01.

Critical Role of the PA-X C-Terminal Domain of Influenza A Virus in Its Subcellular Localization and Shutoff Activity.

Hayashi T, Chaimayo C, McGuinness J, Takimoto T

Journal of virology.. 2016 August 1590 (16):7131-7141. Epub 07/27/2016.

Critical role of Rab11a-mediated recycling endosomes in the assembly of type I parainfluenza viruses.

Stone R, Hayashi T, Bajimaya S, Hodges E, Takimoto T

Virology.. 2016 January 487 :11-8. Epub 10/17/2015.

Impact of influenza PA-X on host response.

Hayashi T, Chaimayo C, Takimoto T

Oncotarget.. 2015 August 146 (23):19364-5. Epub 1900 01 01.

Identification of Influenza A Virus PB2 Residues Involved in Enhanced Polymerase Activity and Virus Growth in Mammalian Cells at Low Temperatures.

Hayashi T, Wills S, Bussey KA, Takimoto T

Journal of virology.. 2015 August 89 (15):8042-9. Epub 05/27/2015.

Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the Host Antiviral and Immune Responses.

Hayashi T, MacDonald LA, Takimoto T

Journal of virology.. 2015 June 89 (12):6442-52. Epub 04/08/2015.

Amino acid substitutions contributing to ?2,6-sialic acid linkage binding specificity of human parainfluenza virus type 3 hemagglutinin-neuraminidase.

Fukushima K, Takahashi T, Ueyama H, Takaguchi M, Ito S, Oishi K, Minami A, Ishitsubo E, Tokiwa H, Takimoto T, Suzuki T

FEBS letters.. 2015 May 8589 (11):1278-82. Epub 04/11/2015.

Sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against RSV in cotton rats.

Zhan X, Slobod KS, Jones BG, Sealy RE, Takimoto T, Boyd K, Surman S, Russell CJ, Portner A, Hurwitz JL

International immunology.. 2015 May 27 (5):229-36. Epub 12/04/2014.

Terminal sialic acid linkages determine different cell infectivities of human parainfluenza virus type 1 and type 3.

Fukushima K, Takahashi T, Ito S, Takaguchi M, Takano M, Kurebayashi Y, Oishi K, Minami A, Kato T, Park EY, Nishimura H, Takimoto T, Suzuki T

Virology.. 2014 September 464-465 :424-431. Epub 08/21/2014.

Specific nucleoprotein residues affect influenza virus morphology.

Bialas KM, Bussey KA, Stone RL, Takimoto T

Journal of virology.. 2014 February 88 (4):2227-34. Epub 12/11/2013.

Identification of the N-terminal domain of the influenza virus PA responsible for the suppression of host protein synthesis.

Desmet EA, Bussey KA, Stone R, Takimoto T

Journal of virology.. 2013 March 87 (6):3108-18. Epub 01/02/2013.

Critical role of the fusion protein cytoplasmic tail sequence in parainfluenza virus assembly.

Stone R, Takimoto T

PloS one.. 2013 8 (4):e61281. Epub 04/12/2013.

Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.

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

Journal of virology.. 2012 May 86 (10):5857-66. Epub 03/07/2012.

Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies.

MacDonald LA, Aggarwal S, Bussey KA, Desmet EA, Kim B, Takimoto T

Virology.. 2012 April 25426 (1):51-9. Epub 02/08/2012.

Sendai virus-based RSV vaccine protects African green monkeys from RSV infection.

Jones BG, Sealy R, Rudraraju R, Traina-Dorge V, Finneyfrock B, Cook A, Takimoto T, Portner A, Hurwitz JL

Vaccine.. 2012 January 2030 (5):959-68. Epub 11/23/2011.

Biochemical impact of the host adaptation-associated PB2 E627K mutation on the temperature-dependent RNA synthesis kinetics of influenza A virus polymerase complex.

Aggarwal S, Dewhurst S, Takimoto T, Kim B

The Journal of biological chemistry.. 2011 October 7286 (40):34504-13. Epub 08/04/2011.

Biophysical analysis of influenza A virus RNA promoter at physiological temperatures.

Noble E, Mathews DH, Chen JL, Turner DH, Takimoto T, Kim B

The Journal of biological chemistry.. 2011 July 1286 (26):22965-70. Epub 05/09/2011.

PA residues in the 2009 H1N1 pandemic influenza virus enhance avian influenza virus polymerase activity in mammalian cells.

Bussey KA, Desmet EA, Mattiacio JL, Hamilton A, Bradel-Tretheway B, Bussey HE, Kim B, Dewhurst S, Takimoto T

Journal of virology.. 2011 July 85 (14):7020-8. Epub 05/11/2011.

T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model.

Guo H, Santiago F, Lambert K, Takimoto T, Topham DJ

Journal of virology.. 2011 January 85 (1):448-55. Epub 10/27/2010.

Trafficking of Sendai virus nucleocapsids is mediated by intracellular vesicles.

Chambers R, Takimoto T

PloS one.. 2010 June 75 (6):e10994. Epub 06/07/2010.

Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells.

Desmet EA, Hollenbaugh JA, Sime PJ, Wright TW, Topham DJ, Sant AJ, Takimoto T, Dewhurst S, Maggirwar SB

Virology.. 2010 May 10400 (2):224-32. Epub 02/25/2010.

PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells.

Bussey KA, Bousse TL, Desmet EA, Kim B, Takimoto T

Journal of virology.. 2010 May 84 (9):4395-406. Epub 02/24/2010.

Biochemical characterization of enzyme fidelity of influenza A virus RNA polymerase complex.

Aggarwal S, Bradel-Tretheway B, Takimoto T, Dewhurst S, Kim B

PloS one.. 2010 April 295 (4):e10372. Epub 04/29/2010.

Antagonism of innate immunity by paramyxovirus accessory proteins.

Chambers R, Takimoto T

Viruses.. 2009 December 1 (3):574-93. Epub 10/28/2009.

Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products.

Chambers R, Takimoto T

The Journal of general virology.. 2009 August 90 (Pt 8):1906-15. Epub 05/07/2009.

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.

Bradel-Tretheway BG, Kelley Z, Chakraborty-Sett S, Takimoto T, Kim B, Dewhurst S

The Journal of general virology.. 2008 December 89 (Pt 12):2923-32. Epub 1900 01 01.

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.

Zhan X, Slobod KS, Krishnamurthy S, Luque LE, Takimoto T, Jones B, Surman S, Russell CJ, Portner A, Hurwitz JL

Vaccine.. 2008 June 2526 (27-28):3480-8. Epub 05/01/2008.

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.

Zhan X, Hurwitz JL, Krishnamurthy S, Takimoto T, Boyd K, Scroggs RA, Surman S, Portner A, Slobod KS

Vaccine.. 2007 December 1725 (52):8782-93. Epub 11/05/2007.

A recombinant Sendai virus is controlled by CD4+ effector T cells responding to a secreted human immunodeficiency virus type 1 envelope glycoprotein.

Brown SA, Hurwitz JL, Zirkel A, Surman S, Takimoto T, Alymova I, Coleclough C, Portner A, Doherty PC, Slobod KS

Journal of virology.. 2007 November 81 (22):12535-42. Epub 07/25/2007.

Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment.

Bousse T, Chambers RL, Scroggs RA, Portner A, Takimoto T

Virus research.. 2006 October 121 (1):23-32. Epub 05/03/2006.

Mutation at residue 523 creates a second receptor binding site on human parainfluenza virus type 1 hemagglutinin-neuraminidase protein.

Bousse T, Takimoto T

Journal of virology.. 2006 September 80 (18):9009-16. Epub 1900 01 01.

Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines.

Krishnamurthy S, Takimoto T, Scroggs RA, Portner A

Journal of virology.. 2006 June 80 (11):5145-55. Epub 1900 01 01.

The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae.

Alymova IV, Portner A, Takimoto T, Boyd KL, Babu YS, McCullers JA

Antimicrobial agents and chemotherapy.. 2005 January 49 (1):398-405. Epub 1900 01 01.

Recombinant Sendai virus as a novel vaccine candidate for respiratory syncytial virus.

Takimoto T, Hurwitz JL, Zhan X, Krishnamurthy S, Prouser C, Brown B, Coleclough C, Boyd K, Scroggs RA, Portner A, Slobod KS

Viral immunology.. 2005 18 (2):255-66. Epub 1900 01 01.

Biological significance of the second receptor binding site of Newcastle disease virus hemagglutinin-neuraminidase protein.

Bousse TL, Taylor G, Krishnamurthy S, Portner A, Samal SK, Takimoto T

Journal of virology.. 2004 December 78 (23):13351-5. Epub 1900 01 01.

Molecular mechanism of paramyxovirus budding.

Takimoto T, Portner A

Virus research.. 2004 December 106 (2):133-45. Epub 1900 01 01.

Recombinant Sendai virus expressing the G glycoprotein of respiratory syncytial virus (RSV) elicits immune protection against RSV.

Takimoto T, Hurwitz JL, Coleclough C, Prouser C, Krishnamurthy S, Zhan X, Boyd K, Scroggs RA, Brown B, Nagai Y, Portner A, Slobod KS

Journal of virology.. 2004 June 78 (11):6043-7. Epub 1900 01 01.

Efficacy of novel hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo.

Alymova IV, Taylor G, Takimoto T, Lin TH, Chand P, Babu YS, Li C, Xiong X, Portner A

Antimicrobial agents and chemotherapy.. 2004 May 48 (5):1495-502. Epub 1900 01 01.

Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion.

Zaitsev V, von Itzstein M, Groves D, Kiefel M, Takimoto T, Portner A, Taylor G

Journal of virology.. 2004 April 78 (7):3733-41. Epub 1900 01 01.

Role of the hemagglutinin-neuraminidase protein in the mechanism of paramyxovirus-cell membrane fusion.

Takimoto T, Taylor GL, Connaris HC, Crennell SJ, Portner A

Journal of virology.. 2002 December 76 (24):13028-33. Epub 1900 01 01.

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.

Bousse T, Matrosovich T, Portner A, Kato A, Nagai Y, Takimoto T

Journal of virology.. 2002 August 76 (16):8244-51. Epub 1900 01 01.

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.

Connaris H, Takimoto T, Russell R, Crennell S, Moustafa I, Portner A, Taylor G

Journal of virology.. 2002 February 76 (4):1816-24. Epub 1900 01 01.

Role of matrix and fusion proteins in budding of Sendai virus.

Takimoto T, Murti KG, Bousse T, Scroggs RA, Portner A

Journal of virology.. 2001 December 75 (23):11384-91. Epub 1900 01 01.

Two regions of the P protein are required to be active with the L protein for human parainfluenza virus type 1 RNA polymerase activity.

Bousse T, Takimoto T, Matrosovich T, Portner A

Virology.. 2001 May 10283 (2):306-14. Epub 1900 01 01.

Receptor specificities of human respiroviruses.

Suzuki T, Portner A, Scroggs RA, Uchikawa M, Koyama N, Matsuo K, Suzuki Y, Takimoto T

Journal of virology.. 2001 May 75 (10):4604-13. Epub 1900 01 01.

Nucleocapsid incorporation into parainfluenza virus is regulated by specific interaction with matrix protein.

Coronel EC, Takimoto T, Murti KG, Varich N, Portner A

Journal of virology.. 2001 February 75 (3):1117-23. Epub 1900 01 01.

Crystal structure of the multifunctional paramyxovirus hemagglutinin-neuraminidase.

Crennell S, Takimoto T, Portner A, Taylor G

Nature structural biology.. 2000 November 7 (11):1068-74. Epub 1900 01 01.

Molecular cloning and expression of human parainfluenza virus type 1 L gene.

Takimoto T, Bousse T, Portner A

Virus research.. 2000 September 70 (1-2):45-53. Epub 1900 01 01.

Crystallization of Newcastle disease virus hemagglutinin-neuraminidase glycoprotein.

Takimoto T, Taylor GL, Crennell SJ, Scroggs RA, Portner A

Virology.. 2000 April 25270 (1):208-14. Epub 1900 01 01.

DNA vaccination as a tool to identify subdominant CD8 T cell epitopes.

Chen Y, Takimoto T, Liu L, Surman S, Woodland DL

Vaccine.. 1999 November 1218 (7-8):720-7. Epub 1900 01 01.

Cytoplasmic domain of Sendai virus HN protein contains a specific sequence required for its incorporation into virions.

Takimoto T, Bousse T, Coronel EC, Scroggs RA, Portner A

Journal of virology.. 1998 December 72 (12):9747-54. Epub 1900 01 01.

Elevated expression of the human parainfluenza virus type 1 F gene downregulates HN expression.

Bousse T, Takimoto T, Murti KG, Portner A

Virology.. 1997 May 26232 (1):44-52. Epub 1900 01 01.

Regions on the hemagglutinin-neuraminidase proteins of human parainfluenza virus type-1 and Sendai virus important for membrane fusion.

Bousse T, Takimoto T, Gorman WL, Takahashi T, Portner A

Virology.. 1994 November 1204 (2):506-14. Epub 1900 01 01.

Mice lacking CD8+ T cells develop greater numbers of IgA-producing cells in response to a respiratory virus infection.

Hyland L, Hou S, Coleclough C, Takimoto T, Doherty PC

Virology.. 1994 October 204 (1):234-41. Epub 1900 01 01.

The human parainfluenza virus type-1 prototypic strain contains a heat-labile hemagglutinin-neuraminidase protein.

Takimoto T, Portner A

Virus research.. 1994 April 32 (1):85-92. Epub 1900 01 01.

Viral cross-reactivity and antigenic determinants recognized by human parainfluenza virus type 1-specific cytotoxic T-cells.

Dave VP, Allan JE, Slobod KS, Smith FS, Ryan KW, Takimoto T, Power UF, Portner A, Hurwitz JL

Virology.. 1994 March 199 (2):376-83. Epub 1900 01 01.

Crystals of hemagglutinin-neuraminidase of parainfluenza virus contain triple-stranded helices.

Murti KG, Takimoto T, Laver WG, Portner A

Proceedings of the National Academy of Sciences of the United States of America.. 1993 February 1590 (4):1523-5. Epub 1900 01 01.

Crystallization of biologically active hemagglutinin-neuraminidase glycoprotein dimers proteolytically cleaved from human parainfluenza virus type 1.

Takimoto T, Laver WG, Murti KG, Portner A

Journal of virology.. 1992 December 66 (12):7597-600. Epub 1900 01 01.

Books

Encyclopedia of Life Sciences (2006)

Chapter: Parainfluenza viruses. (version 2.0) Encyclopedia of Life Sciences. John Wiley & Sons, Ltd. 2006.

Authors: Takimoto T

Publisher: John Wiley & Sons, Ltd. 2006

Nature Encyclopedia of Life Science (2002)

Chapter: Parainfluenza viruses. Nature Encyclopedia of Life Science. Nature Publishing Group. 2002.

Authors: Takimoto T.

Publisher: Nature Publishing Group 2002