Terence Dermody
Last active: 4/25/2016

Profile

Our lab studies the molecular pathogenesis of mammalian reovirus and chikungunya virus infections. Reovirus is an enteric, neurotropic virus that infects many mammalian species, including humans, but disease is restricted to the very young. Chikungunya virus is an emerging arthropod-borne alphavirus that causes epidemics of febrile arthritis in humans. Research in my laboratory encompasses several interrelated themes to better understand viral and cellular mediators of disease. These include the structural basis of viral attachment and entry into cells, mechanisms of genome replication and packaging, patterns of cell signaling and gene expression occurring in response to viral infection, mechanisms of virus-induced apoptosis and its significance in the viral life cycle, and roles of viral receptor distribution and utilization in disease pathology. We also are developing viral vectors for oncolytic and vaccine applications.

(1) Reovirus receptors and pathogenesis. Following peroral inoculation of newborn mice, reovirus disseminates systemically to target the heart, liver, and central nervous system. We are conducting experiments to investigate the role of reovirus receptors, sialic acid, junctional adhesion molecule A (JAM-A), and Nogo receptor-1 (NgR1) in reovirus dissemination and tropism. These studies employ primary cells and mice lacking reovirus receptors. This work will be interpreted in the context of ongoing studies to determine the structure of reovirus in complex with its receptors. Since not all of the reovirus receptors are known, we are working to identify additional reovirus receptors.

(2) Reovirus cell entry and replication. Reovirus enters cells by clathrin-dependent endocytosis in an integrin-dependent process and undergoes proteolytic disassembly in endosomes. Studies are in progress to define mechanisms of reovirus uptake and transport within the endocytic pathway. We also are working to define how the viral gene products reorganize cellular architecture to form the viral replication organelles that serve as sites for genome replication and particle assembly. This research will reveal mechanisms by which viral and cellular factors cooperate to facilitate viral replication and illuminate new targets for therapeutic intervention.

(3) Reovirus-induced apoptosis. Reovirus induces apoptosis in cultured cells and in the murine central nervous system and heart. Our studies indicate that apoptosis is triggered by innate immune response signal transducers initiated by viral components following reovirus disassembly and penetration of endosomal membranes. Experiments are in progress to identify components of the cell-signaling apparatus required for apoptosis induction by reovirus and to determine the relationship between apoptosis and virulence. These studies will establish new ideas about how RNA-containing viruses interact with innate immune response signaling circuits and lead to a better understanding of how viruses injure their host cells.

(4) Chikungunya virus (CHIKV) attachment and cell entry. CHIKV has produced explosive outbreaks in East Africa, several islands in the Indian Ocean, India, Southeast Asia, and most recently the Caribbean. We have found that attenuated CHIKV vaccine strain 181/25 engages heparan sulfate proteoglycans to initiate infection. Ongoing work is focused on identification of host cell proteins that contribute to CHIKV attachment and internalization and definition of CHIKV virulence determinants. This research will fill major gaps in an understanding of CHIKV pathogenesis and illuminate new targets for antiviral therapies and vaccines.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Human Metapneumovirus Is Capable of Entering Cells by Fusion with Endosomal Membranes. Cox RG, Mainou BA, Johnson M, Hastings AK, Schuster JE, Dermody TS, Williams JV (2015) PLoS Pathog 11(12): e1005303
    › Primary publication · 26629703 (PubMed) · PMC4667933 (PubMed Central)
  2. Comparison of three neurotropic viruses reveals differences in viral dissemination to the central nervous system. Luethy LN, Erickson AK, Jesudhasan PR, Ikizler M, Dermody TS, Pfeiffer JK (2016) Virology : 1-10
    › Primary publication · 26479325 (PubMed) · PMC4679581 (PubMed Central)
  3. Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus. Smith SA, Silva LA, Fox JM, Flyak AI, Kose N, Sapparapu G, Khomandiak S, Khomadiak S, Ashbrook AW, Kahle KM, Fong RH, Swayne S, Doranz BJ, McGee CE, Heise MT, Pal P, Brien JD, Austin SK, Diamond MS, Dermody TS, Crowe JE (2015) Cell Host Microbe 18(1): 86-95
    › Primary publication · 26159721 (PubMed) · PMC4501771 (PubMed Central)
  4. Serotonin Receptor Agonist 5-Nonyloxytryptamine Alters the Kinetics of Reovirus Cell Entry. Mainou BA, Ashbrook AW, Smith EC, Dorset DC, Denison MR, Dermody TS (2015) J Virol 89(17): 8701-12
    › Primary publication · 26109733 (PubMed) · PMC4524060 (PubMed Central)
  5. Structure of Serotype 1 Reovirus Attachment Protein σ1 in Complex with Junctional Adhesion Molecule A Reveals a Conserved Serotype-Independent Binding Epitope. Stettner E, Dietrich MH, Reiss K, Dermody TS, Stehle T (2015) J Virol 89(11): 6136-40
    › Primary publication · 25810543 (PubMed) · PMC4442426 (PubMed Central)
  6. Diminished reovirus capsid stability alters disease pathogenesis and littermate transmission. Doyle JD, Stencel-Baerenwald JE, Copeland CA, Rhoads JP, Brown JJ, Boyd KL, Atkinson JB, Dermody TS (2015) PLoS Pathog 11(3): e1004693
    › Primary publication · 25738608 (PubMed) · PMC4349883 (PubMed Central)
  7. Glycan engagement dictates hydrocephalus induction by serotype 1 reovirus. Stencel-Baerenwald J, Reiss K, Blaum BS, Colvin D, Li XN, Abel T, Boyd K, Stehle T, Dermody TS (2015) MBio 6(2): e02356
    › Primary publication · 25736887 (PubMed) · PMC4358001 (PubMed Central)
  8. Correction for Fernández de Castro et al., Reovirus Forms Neo-Organelles for Progeny Particle Assembly within Reorganized Cell Membranes. Fernández de Castro I, Zamora PF, Ooms L, Fernández JJ, Lai CM, Mainou BA, Dermody TS, Risco C (2015) MBio 6(1)
    › Primary publication · 25626908 (PubMed) · PMC4323419 (PubMed Central)
  9. Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL, Crawford SE, Pruijssers AJ, Iskarpatyoti JA, Estes MK, Dermody TS, Ouyang W, Williams IR, Vijay-Kumar M, Gewirtz AT (2014) Science 346(6211): 861-5
    › Primary publication · 25395539 (PubMed) · PMC4788408 (PubMed Central)
  10. The decision to publish an avian H7N1 influenza virus gain-of-function experiment. Dermody TS, Casadevall A, Imperiale MJ, Sandri-Goldin RM, Shenk T (2014) MBio 5(5): e01985-14
    › Primary publication · 25316699 (PubMed) · PMC4205794 (PubMed Central)
  11. The sweet spot: defining virus-sialic acid interactions. Stencel-Baerenwald JE, Reiss K, Reiter DM, Stehle T, Dermody TS (2014) Nat Rev Microbiol 12(11): 739-49
    › Primary publication · 25263223 (PubMed) · PMC4791167 (PubMed Central)
  12. Endothelial JAM-A promotes reovirus viremia and bloodstream dissemination. Lai CM, Boehme KW, Pruijssers AJ, Parekh VV, Van Kaer L, Parkos CA, Dermody TS (2015) J Infect Dis 211(3): 383-93
    › Primary publication · 25149763 (PubMed) · PMC4351375 (PubMed Central)
  13. Residue 82 of the Chikungunya virus E2 attachment protein modulates viral dissemination and arthritis in mice. Ashbrook AW, Burrack KS, Silva LA, Montgomery SA, Heise MT, Morrison TE, Dermody TS (2014) J Virol 88(21): 12180-92
    › Primary publication · 25142598 (PubMed) · PMC4248890 (PubMed Central)
  14. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Goubau D, Schlee M, Deddouche S, Pruijssers AJ, Zillinger T, Goldeck M, Schuberth C, Van der Veen AG, Fujimura T, Rehwinkel J, Iskarpatyoti JA, Barchet W, Ludwig J, Dermody TS, Hartmann G, Reis e Sousa C (2014) Nature 514(7522): 372-375
    › Primary publication · 25119032 (PubMed) · PMC4201573 (PubMed Central)
  15. The Nogo receptor NgR1 mediates infection by mammalian reovirus. Konopka-Anstadt JL, Mainou BA, Sutherland DM, Sekine Y, Strittmatter SM, Dermody TS (2014) Cell Host Microbe 15(6): 681-91
    › Primary publication · 24922571 (PubMed) · PMC4100558 (PubMed Central)
  16. Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns in discrete brain regions. Hood JL, Morabito MV, Martinez CR, Gilbert JA, Ferrick EA, Ayers GD, Chappell JD, Dermody TS, Emeson RB (2014) Mol Cell Neurosci : 97-109
    › Primary publication · 24906008 (PubMed) · PMC4134954 (PubMed Central)
  17. Repurposing staples for viruses: applying peptide design to RSV prophylaxis. Katen SP, Dermody TS (2014) J Clin Invest 124(5): 1889-91
    › Primary publication · 24743141 (PubMed) · PMC4001561 (PubMed Central)
  18. Efficient norovirus and reovirus replication in the mouse intestine requires microfold (M) cells. Gonzalez-Hernandez MB, Liu T, Payne HC, Stencel-Baerenwald JE, Ikizler M, Yagita H, Dermody TS, Williams IR, Wobus CE (2014) J Virol 88(12): 6934-43
    › Primary publication · 24696493 (PubMed) · PMC4054386 (PubMed Central)
  19. On the need for a national board to assess dual use research of concern. Casadevall A, Dermody TS, Imperiale MJ, Sandri-Goldin RM, Shenk T (2014) J Virol 88(12): 6535-7
    › Primary publication · 24696484 (PubMed) · PMC4054389 (PubMed Central)
  20. Sequence changes associated with respiratory transmission of H7N1 influenza virus in mammals. Dermody TS, Sandri-Goldin RM, Shenk T (2014) J Virol 88(12): 6533-4
    › Primary publication · 24696481 (PubMed) · PMC4054340 (PubMed Central)
  21. Trans-dimerization of JAM-A regulates Rap2 and is mediated by a domain that is distinct from the cis-dimerization interface. Monteiro AC, Luissint AC, Sumagin R, Lai C, Vielmuth F, Wolf MF, Laur O, Reiss K, Spindler V, Stehle T, Dermody TS, Nusrat A, Parkos CA (2014) Mol Biol Cell 25(10): 1574-85
    › Primary publication · 24672055 (PubMed) · PMC4019489 (PubMed Central)
  22. Reovirus forms neo-organelles for progeny particle assembly within reorganized cell membranes. Fernández de Castro I, Zamora PF, Ooms L, Fernández JJ, Lai CM, Mainou BA, Dermody TS, Risco C (2014) MBio 5(1)
    › Primary publication · 24549844 (PubMed) · PMC3944815 (PubMed Central)
  23. A single-amino-acid polymorphism in Chikungunya virus E2 glycoprotein influences glycosaminoglycan utilization. Silva LA, Khomandiak S, Ashbrook AW, Weller R, Heise MT, Morrison TE, Dermody TS (2014) J Virol 88(5): 2385-97
    › Primary publication · 24371059 (PubMed) · PMC3958064 (PubMed Central)
  24. An ITAM in a nonenveloped virus regulates activation of NF-κB, induction of beta interferon, and viral spread. Stebbing RE, Irvin SC, Rivera-Serrano EE, Boehme KW, Ikizler M, Yoder JA, Dermody TS, Sherry B (2014) J Virol 88(5): 2572-83
    › Primary publication · 24352448 (PubMed) · PMC3958081 (PubMed Central)
  25. A plasmid-based reverse genetics system for mammalian orthoreoviruses driven by a plasmid-encoded T7 RNA polymerase. Komoto S, Kawagishi T, Kobayashi T, Ikizler M, Iskarpatyoti J, Dermody TS, Taniguchi K (2014) J Virol Methods : 36-9
    › Primary publication · 24183920 (PubMed)
  26. The invasive chytrid fungus of amphibians paralyzes lymphocyte responses. Fites JS, Ramsey JP, Holden WM, Collier SP, Sutherland DM, Reinert LK, Gayek AS, Dermody TS, Aune TM, Oswald-Richter K, Rollins-Smith LA (2013) Science 342(6156): 366-9
    › Primary publication · 24136969 (PubMed) · PMC3956111 (PubMed Central)
  27. Apoptosis induction influences reovirus replication and virulence in newborn mice. Pruijssers AJ, Hengel H, Abel TW, Dermody TS (2013) J Virol 87(23): 12980-9
    › Primary publication · 24067960 (PubMed) · PMC3838116 (PubMed Central)
  28. Nonstructural protein σ1s mediates reovirus-induced cell cycle arrest and apoptosis. Boehme KW, Hammer K, Tollefson WC, Konopka-Anstadt JL, Kobayashi T, Dermody TS (2013) J Virol 87(23): 12967-79
    › Primary publication · 24067959 (PubMed) · PMC3838159 (PubMed Central)
  29. Reovirus receptors, cell entry, and proapoptotic signaling. Danthi P, Holm GH, Stehle T, Dermody TS (2013) Adv Exp Med Biol : 42-71
    › Primary publication · 23884585 (PubMed) · PMC4724410 (PubMed Central)
  30. Reovirus cell entry requires functional microtubules. Mainou BA, Zamora PF, Ashbrook AW, Dorset DC, Kim KS, Dermody TS (2013) MBio 4(4)
    › Primary publication · 23820395 (PubMed) · PMC3705452 (PubMed Central)
  31. Genetic determinants of reovirus pathogenesis in a murine model of respiratory infection. Nygaard RM, Lahti L, Boehme KW, Ikizler M, Doyle JD, Dermody TS, Schiff LA (2013) J Virol 87(16): 9279-89
    › Primary publication · 23760238 (PubMed) · PMC3754055 (PubMed Central)
  32. A new determinant of H5N1 influenza virus pathogenesis in mammals. Dermody TS, Sandri-Goldin RM, Shenk T (2013) J Virol 87(9): 4795-6
    › Primary publication · 23449798 (PubMed) · PMC3624319 (PubMed Central)
  33. Mutations in the rotavirus spike protein VP4 reduce trypsin sensitivity but not viral spread. Trask SD, Wetzel JD, Dermody TS, Patton JT (2013) J Gen Virol 94(Pt 6): 1296-300
    › Primary publication · 23426355 (PubMed) · PMC3709623 (PubMed Central)
  34. The GM2 glycan serves as a functional coreceptor for serotype 1 reovirus. Reiss K, Stencel JE, Liu Y, Blaum BS, Reiter DM, Feizi T, Dermody TS, Stehle T (2012) PLoS Pathog 8(12): e1003078
    › Primary publication · 23236285 (PubMed) · PMC3516570 (PubMed Central)
  35. Comparative analysis of Reoviridae reverse genetics methods. Trask SD, Boehme KW, Dermody TS, Patton JT (2013) Methods 59(2): 199-206
    › Primary publication · 22687622 (PubMed) · PMC3449048 (PubMed Central)
  36. Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling. Bozym RA, Delorme-Axford E, Harris K, Morosky S, Ikizler M, Dermody TS, Sarkar SN, Coyne CB (2012) Cell Host Microbe 11(2): 153-66
    › Primary publication · 22341464 (PubMed) · PMC3995454 (PubMed Central)
  37. A single-amino-acid polymorphism in reovirus protein μ2 determines repression of interferon signaling and modulates myocarditis. Irvin SC, Zurney J, Ooms LS, Chappell JD, Dermody TS, Sherry B (2012) J Virol 86(4): 2302-11
    › Primary publication · 22156521 (PubMed) · PMC3302381 (PubMed Central)
  38. Apoptosis induced by mammalian reovirus is beta interferon (IFN) independent and enhanced by IFN regulatory factor 3- and NF-κB-dependent expression of Noxa. Knowlton JJ, Dermody TS, Holm GH (2012) J Virol 86(3): 1650-60
    › Primary publication · 22090144 (PubMed) · PMC3264342 (PubMed Central)
  39. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Kuss SK, Best GT, Etheredge CA, Pruijssers AJ, Frierson JM, Hooper LV, Dermody TS, Pfeiffer JK (2011) Science 334(6053): 249-52
    › Primary publication · 21998395 (PubMed) · PMC3222156 (PubMed Central)
  40. Crystal structure of reovirus attachment protein σ1 in complex with sialylated oligosaccharides. Reiter DM, Frierson JM, Halvorson EE, Kobayashi T, Dermody TS, Stehle T (2011) PLoS Pathog 7(8): e1002166
    › Primary publication · 21829363 (PubMed) · PMC3150272 (PubMed Central)