Rebecca Dutch

Bio / Education: 

Ph.D., Biochemistry, Stanford University, 1994
M.Phil., Biochemistry, Cambridge University, 1987
B.S., Biochemistry and B.S. Microbiology, Michigan State University, 1986

Research Description: 

The central focus of our research is the synthesis, folding, processing and function of viral glycoproteins. Previous studies of the synthesis and processing of viral glycoproteins in the secretory pathway have led to fundamental discoveries of basic cellular processes, and our research on the folding and processing of paramyxovirus glycoproteins provides insight into both cellular functions and important viral proteins. Our studies on viral proteins aim to elucidate mechanisms of promotion of membrane fusion, and to provide new targets for antiviral treatments.

Many major human pathogenic viruses (including HIV, herpes simplex virus, measles virus and Ebola virus) are packaged in a membrane. In order for these viruses to infect cells, specific viral proteins promote fusion of the viral membrane with the membrane of the host cell. Understanding this process of protein-mediated membrane fusion is the major focus of our work. We study fusion proteins from several different paramyxoviruses. First, we are examining the fusion protein from the Hendra and Nipah viruses, newly emerged diseases in the paramyxovirus family that are highly pathogenic in multiple species including humans, and which are classified as Biosafety Level 4 pathogens. Our laboratory has identified cathepsin L, a cellular endosomal/lysosomal protease, as critical protein for activation of the Hendra and Nipah fusion proteins, and thus a potential drug target. We are also studying the F protein from the paramxyovirus SV5, for which multiple mutants have been made and for which several atomic structures are now known. Finally, we have initiated study of the glycoproteins from human metapneumovirus, a recently identified virus that is a causative agent of severe respiratory disease in infants and young children. Our long-term goal is to understand the specific molecular events in these important membrane fusion processes.

PubMed Publications: 

  • Klimyte, E.M.;Smith, S.E.;Oreste, P.;Lembo, D.;Dutch, R.E. "Inhibition of human metapneumovirus binding to heparan sulfate blocks infection in human lung cells and airway tissues." Journal of virology (2016): [PubMed Link] | [ Full text ]
  • Chai, Q.;Webb, S.R.;Wang, Z.;Dutch, R.E.;Wei, Y. "Study of the degradation of a multidrug transporter using a non-radioactive pulse chase method." Analytical and bioanalytical chemistry (2016): [PubMed Link] | [ Full text ]
  • Chai, Q.;Wang, Z.;Webb, S.R.;Dutch, R.E.;Wei, Y. "The ssrA-Tag Facilitated Degradation of an Integral Membrane Protein." Biochemistry 55, 16 (2016): 2301-4. [PubMed Link] | [ Full text ]
  • El Najjar, F.;Lampe, L.;Baker, M.L.;Wang, L.F.;Dutch, R.E. "Analysis of cathepsin and furin proteolytic enzymes involved in viral fusion protein activation in cells of the bat reservoir host." PloS one 10, 2 (2015): e0115736. [PubMed Link] | [ Full text ]
  • Masante, C.;El Najjar, F.;Chang, A.;Jones, A.;Moncman, C.L.;Dutch, R.E. "The human metapneumovirus small hydrophobic protein has properties consistent with those of a viroporin and can modulate viral fusogenic activity." Journal of virology 88, 11 (2014): 6423-33. [PubMed Link] | [ Full text ]
  • Amarasinghe, G.K.;Dutch, R.E. "A calcium-fortified viral matrix protein." Structure (London, England : 1993) 22, 1 (2014): 5-7. [PubMed Link] | [ Full text ]
  • El Najjar, F.;Schmitt, A.P.;Dutch, R.E. "Paramyxovirus glycoprotein incorporation, assembly and budding: a three way dance for infectious particle production." Viruses 6, 8 (2014): 3019-54. [PubMed Link] | [ Full text ]
  • Smith, E.C.;Smith, S.E.;Carter, J.R.;Webb, S.R.;Gibson, K.M.;Hellman, L.M.;Fried, M.G.;Dutch, R.E. "Trimeric transmembrane domain interactions in paramyxovirus fusion proteins: roles in protein folding, stability, and function." The Journal of biological chemistry 288, 50 (2013): 35726-35. [PubMed Link] | [ Full text ]
  • Chang, A.;Hackett, B.A.;Winter, C.C.;Buchholz, U.J.;Dutch, R.E. "Potential electrostatic interactions in multiple regions affect human metapneumovirus F-mediated membrane fusion." Journal of virology 86, 18 (2012): 9843-53. [PubMed Link] | [ Full text ]
  • Popa, A.;Carter, J.R.;Smith, S.E.;Hellman, L.;Fried, M.G.;Dutch, R.E. "Residues in the hendra virus fusion protein transmembrane domain are critical for endocytic recycling." Journal of virology 86, 6 (2012): 3014-26. [PubMed Link] | [ Full text ]
  • Chang, A.;Masante, C.;Buchholz, U.J.;Dutch, R.E. "Human metapneumovirus (HMPV) binding and infection are mediated by interactions between the HMPV fusion protein and heparan sulfate." Journal of virology 86, 6 (2012): 3230-43. [PubMed Link] | [ Full text ]
  • Smith, E.C.;Culler, M.R.;Hellman, L.M.;Fried, M.G.;Creamer, T.P.;Dutch, R.E. "Beyond anchoring: the expanding role of the hendra virus fusion protein transmembrane domain in protein folding, stability, and function." Journal of virology 86, 6 (2012): 3003-13. [PubMed Link] | [ Full text ]
  • Smith, E.C.;Gregory, S.M.;Tamm, L.K.;Creamer, T.P.;Dutch, R.E. "Role of sequence and structure of the Hendra fusion protein fusion peptide in membrane fusion." The Journal of biological chemistry 287, 35 (2012): 30035-48. [PubMed Link] | [ Full text ]
  • Chang, A.;Dutch, R.E. "Paramyxovirus fusion and entry: multiple paths to a common end." Viruses 4, 4 (2012): 613-36. [PubMed Link] | [ Full text ]
  • Popa, A.;Pager, C.T.;Dutch, R.E. "C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein." Biochemistry 50, 6 (2011): 945-52. [PubMed Link] | [ Full text ]
  • Smith, E.C.;Dutch, R.E. "Side chain packing below the fusion peptide strongly modulates triggering of the Hendra virus F protein." Journal of virology 84, 20 (2010): 10928-32. [PubMed Link] | [ Full text ]
  • Dutch, R.E. "Entry and fusion of emerging paramyxoviruses." PLoS pathogens 6, 6 (2010): e1000881. [PubMed Link] | [ Full text ]
  • Wurth, M.A.;Schowalter, R.M.;Smith, E.C.;Moncman, C.L.;Dutch, R.E.;McCann, R.O. "The actin cytoskeleton inhibits pore expansion during PIV5 fusion protein-promoted cell-cell fusion." Virology 404, 1 (2010): 117-26. [PubMed Link] | [ Full text ]
  • Whitman, S.D.;Smith, E.C.;Dutch, R.E. "Differential rates of protein folding and cellular trafficking for the Hendra virus F and G proteins: implications for F-G complex formation." Journal of virology 83, 17 (2009): 8998-9001. [PubMed Link] | [ Full text ]
  • Schowalter, R.M.;Chang, A.;Robach, J.G.;Buchholz, U.J.;Dutch, R.E. "Low-pH triggering of human metapneumovirus fusion: essential residues and importance in entry." Journal of virology 83, 3 (2009): 1511-22. [PubMed Link] | [ Full text ]
  • Smith, E.C.;Popa, A.;Chang, A.;Masante, C.;Dutch, R.E. "Viral entry mechanisms: the increasing diversity of paramyxovirus entry." The FEBS journal 276, 24 (2009): 7217-27. [PubMed Link] | [ Full text ]
  • Gardner, A.E.;Martin, K.L.;Dutch, R.E. "A conserved region between the heptad repeats of paramyxovirus fusion proteins is critical for proper F protein folding." Biochemistry 46, 17 (2007): 5094-105. [PubMed Link] | [ Full text ]
  • Whitman, S.D.;Dutch, R.E. "Surface density of the Hendra G protein modulates Hendra F protein-promoted membrane fusion: role for Hendra G protein trafficking and degradation." Virology 363, 2 (2007): 419-29. [PubMed Link] | [ Full text ]
  • Gardner, A.E.;Dutch, R.E. "A conserved region in the F(2) subunit of paramyxovirus fusion proteins is involved in fusion regulation." Journal of virology 81, 15 (2007): 8303-14. [PubMed Link] | [ Full text ]
  • Schowalter, R.M.;Smith, S.E.;Dutch, R.E. "Characterization of human metapneumovirus F protein-promoted membrane fusion: critical roles for proteolytic processing and low pH." Journal of virology 80, 22 (2006): 10931-41. [PubMed Link] | [ Full text ]
  • Pager, C.T.;Craft WW, J.;Patch, J.;Dutch, R.E. "A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L." Virology 346, 2 (2006): 251-7. [PubMed Link] | [ Full text ]
  • Schowalter, R.M.;Wurth, M.A.;Aguilar, H.C.;Lee, B.;Moncman, C.L.;McCann, R.O.;Dutch, R.E. "Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion." Virology 350, 2 (2006): 323-34. [PubMed Link] | [ Full text ]
  • Craft WW, J.;Dutch, R.E. "Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing." Virology 341, 1 (2005): 130-40. [PubMed Link] | [ Full text ]
  • Pager, C.T.;Dutch, R.E. "Cathepsin L is involved in proteolytic processing of the Hendra virus fusion protein." Journal of virology 79, 20 (2005): 12714-20. [PubMed Link] | [ Full text ]
  • Meulendyke, K.A.;Wurth, M.A.;McCann, R.O.;Dutch, R.E. "Endocytosis plays a critical role in proteolytic processing of the Hendra virus fusion protein." Journal of virology 79, 20 (2005): 12643-9. [PubMed Link] | [ Full text ]
  • Carter, J.R.;Pager, C.T.;Fowler, S.D.;Dutch, R.E. "Role of N-linked glycosylation of the Hendra virus fusion protein." Journal of virology 79, 12 (2005): 7922-5. [PubMed Link] | [ Full text ]
  • West, D.S.;Sheehan, M.S.;Segeleon, P.K.;Dutch, R.E. "Role of the simian virus 5 fusion protein N-terminal coiled-coil domain in folding and promotion of membrane fusion." Journal of virology 79, 3 (2005): 1543-51. [PubMed Link] | [ Full text ]
  • Pager, C.T.;Wurth, M.A.;Dutch, R.E. "Subcellular localization and calcium and pH requirements for proteolytic processing of the Hendra virus fusion protein." Journal of virology 78, 17 (2004): 9154-63. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Hagglund, R.N.;Nagel, M.A.;Paterson, R.G.;Lamb, R.A. "Paramyxovirus fusion (F) protein: a conformational change on cleavage activation." Virology 281, 1 (2001): 138-50. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Lamb, R.A. "Deletion of the cytoplasmic tail of the fusion protein of the paramyxovirus simian virus 5 affects fusion pore enlargement." Journal of virology 75, 11 (2001): 5363-9. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Jardetzky, T.S.;Lamb, R.A. "Virus membrane fusion proteins: biological machines that undergo a metamorphosis." Bioscience reports 20, 6 (2000): 597-612. [PubMed Link] | [ Full text ]
  • Baker, K.A.;Dutch, R.E.;Lamb, R.A.;Jardetzky, T.S. "Structural basis for paramyxovirus-mediated membrane fusion." Molecular cell 3, 3 (1999): 309-19. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Leser, G.P.;Lamb, R.A. "Paramyxovirus fusion protein: characterization of the core trimer, a rod-shaped complex with helices in anti-parallel orientation." Virology 254, 1 (1999): 147-59. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Joshi, S.B.;Lamb, R.A. "Membrane fusion promoted by increasing surface densities of the paramyxovirus F and HN proteins: comparison of fusion reactions mediated by simian virus 5 F, human parainfluenza virus type 3 F, and influenza virus HA." Journal of virology 72, 10 (1998): 7745-53. [PubMed Link] | [ Full text ]
  • Joshi, S.B.;Dutch, R.E.;Lamb, R.A. "A core trimer of the paramyxovirus fusion protein: parallels to influenza virus hemagglutinin and HIV-1 gp41." Virology 248, 1 (1998): 20-34. [PubMed Link] | [ Full text ]
  • Zhou, J.;Dutch, R.E.;Lamb, R.A. "Proper spacing between heptad repeat B and the transmembrane domain boundary of the paramyxovirus SV5 F protein is critical for biological activity." Virology 239, 2 (1997): 327-39. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Bianchi, V.;Lehman, I.R. "Herpes simplex virus type 1 DNA replication is specifically required for high-frequency homologous recombination between repeated sequences." Journal of virology 69, 5 (1995): 3084-9. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Zemelman, B.V.;Lehman, I.R. "Herpes simplex virus type 1 recombination: the Uc-DR1 region is required for high-level a-sequence-mediated recombination." Journal of virology 68, 6 (1994): 3733-41. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Lehman, I.R. "Renaturation of complementary DNA strands by herpes simplex virus type 1 ICP8." Journal of virology 67, 12 (1993): 6945-9. [PubMed Link] | [ Full text ]
  • Bruckner, R.C.;Dutch, R.E.;Zemelman, B.V.;Mocarski, E.S.;Lehman, I.R. "Recombination in vitro between herpes simplex virus type 1 a sequences." Proceedings of the National Academy of Sciences of the United States of America 89, 22 (1992): 10950-4. [PubMed Link] | [ Full text ]
  • Dutch, R.E.;Bruckner, R.C.;Mocarski, E.S.;Lehman, I.R. "Herpes simplex virus type 1 recombination: role of DNA replication and viral a sequences." Journal of virology 66, 1 (1992): 277-85. [PubMed Link] | [ Full text ]
  • Hernandez, T.R.;Dutch, R.E.;Lehman, I.R.;Gustafsson, C.;Elias, P. "Mutations in a herpes simplex virus type 1 origin that inhibit interaction with origin-binding protein also inhibit DNA replication." Journal of virology 65, 3 (1991): 1649-52. [PubMed Link] | [ Full text ]