Assistant Research Professor: Tadahisa Teramoto, MD, PhD

Tadhahesia Teramoto

Summary

M.D.: Tottori University, Japan, 1988

Residency: National Kobe Hospital, Japan, 1988-1990

Ph.D.: Kobe University, Japan, 1994

Fellowship: NCI/NIH, 1996-2000, and FDA, 2005-2008

Postdoc at Georgetown: 2002-2003, 2004-2005, 2008-2018

Assistant Professor (research track): 2019-

Currently Funded Research

Two NIH/NIAID funds are supporting my research projects. R01 (02/2018-02/2023) is focused on “Mechanism of RNA synthesis and 5’ capping by Dengue Virus (DENV) NS5.” As the PI, Prof. KH Choi at the University of Texas has analyzed Flavivirus replication from the view of protein and RNA structures. As co-PIs, Emeritus Prof. Padmanabhan and I have analyzed the mechanism behind how NS5 plays roles with NS3 and untranslated regions (UTR). We have created mutated proteins/attenuated viruses and examined the evolutions of viruses. (1-4). We revealed the dimerization of NS5, the correlation between MTase and POL domains within NS5 as well as MTase and NS3 Hel domains, and the role of stem loop region (SLA) at 5’UTR for viral RNA synthesis. I am expanding the analysis on the roles of NS3 Pro and Hel domains in viral replication. R21 (06/2021-05/2023) was recently granted for analyses of “Mechanism of wMelPop-induced DENV2 transmembrane domain mutations in NS2A, NS2B and NS4B.” We have found that DENV2 genome quickly acquires mutations after infecting wMelPop-C6/36 mosquito cells (Ae. albopictus)(5). As the PI, I am analyzing the mechanism of how wMelPop, intra-cellular bacteria chronically infecting insect cells suppresses DENV replication in mosquito cells and induces selective mutations at viral non-structural non-enzymatic proteins (NS2A, NS2B and NS4B). Mutations have been found to occur at transmembrane domains (TMDs) of NS2A, NS2B and NS4B. These mutations were stable in naïve C6/36 mosquito cells, although in BHK-21 mammalian cells, these reverted to wild type sequences, accompanied by additional NS3 mutations. It is known that TMDs in viral proteins are critical for forming viral replication compartment at cellular endoplasmic reticulum (ER). I am expanding the analyses by investigating: 1. Which cellular factor(s) at ER are affected by wMelPop infection? 2. How do individual TMD mutations relate to each other as well as to NS3 mutations? 3. What is the difference of ER environments between naïve mosquito and mammalian cells for supporting DENV replication?

Related Publications

  • Teramoto, T., Boonyasuppayakorn, S., Handley, M., Choi, K. H., and Padmanabhan, R. (2014) Substitution of NS5 N-terminal domain of dengue virus type 2 RNA with type 4 domain caused impaired replication and emergence of adaptive mutants with enhanced fitness. J Biol Chem 289, 22385-22400
  • Klema, V. J., Ye, M., Hindupur, A., Teramoto, T., Gottipati, K., Padmanabhan, R., and Choi, K. H. (2016) Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface. PLoS pathogens 12, e1005451
  • Teramoto, T., Balasubramanian, A., Choi, K. H., and Padmanabhan, R. (2017) Serotype-specific interactions among functional domains of dengue virus 2 nonstructural proteins (NS) 5 and NS3 are crucial for viral RNA replication. J Biol Chem 292, 9465-9479
  • Lee, E., Bujalowski, P. J., Teramoto, T., Gottipati, K., Scott, S. D., Padmanabhan, R., and Choi, K. H. (2021) Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase. Nature communications 12, 2530
  • Teramoto, T., Huang, X., Armbruster, P. A., and Padmanabhan, R. (2019) Infection of Aedes albopictus Mosquito C6/36 Cells with the wMelpop Strain of Wolbachia Modulates Dengue Virus-Induced Host Cellular Transcripts and Induces Critical Sequence Alterations in the Dengue Viral Genome. Journal of virology 93

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