Sue E. Delos

Education

  • PhD, University of Colorado

Contact

Research Interest(s)

Virus-Receptor Interactions; Virus-Cell Fusion Mechanisms

Research Description

The major focus of my laboratory is to elucidate the mechanisms by which enveloped viruses enter cells, an obligate early step in the infection process. The long-term goal of my work is the identification of inhibitors of viral entry. For the enveloped viruses, entry requires fusion of the viral and cellular membranes, an event driven by a carefully orchestrated series of conformational changes in the viral glycoproteins. In collaboration with Dr. Judith M. White, I have used the model α-retrovirus, Avian Sarcoma/Leukosis Virus (ASLV), to characterize the glycoprotein requirements for (a) receptor interactions, and (b) the fusion process. Given the high homology between the fusion subunits of the ASLV and filovirus (ebolavirus (EBOV) and Marburg) glycoproteins, we have been able to compare and contrast features important for entry between the ASLV and EBOV glycoproteins. The α-retroviruses and filoviruses are unique among Class I fusion proteins in having an internal fusion loop flanked by cysteines. We have shown that the cystienes are important for ASLV infectivity and function at the step of lipid mixing. In collaboration with Dr. Lukas Tamm, we are now studying the fusion-relevant membrane interactions of this unusual, internal, cysteine-flanked fusion loop for EBOV. The filoviruses are NIAID Class A priority pathogens of high lethality for which no effective vaccines or therapeutics have been approved. We are currently using our binding and entry assays to screen for compounds that can inhibit EBOV entry and to characterize the mechanism by which they do so. Our work may identify druggable reagents with which to combat this deadly pathogen.

Selected Publications

  • Brecher M, Schornberg K, Delos S, Fusco M, Saphire E, White J. Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change. Journal of virology. 2011;86(1): 364-72. PMID: 22031933 | PMCID: PMC3255896
  • Gregory S, Harada E, Liang B, Delos S, White J, Tamm L. Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(27): 11211-6. PMID: 21690393 | PMCID: PMC3131375
  • Delos S, La B, Gilmartin A, White J. Studies of the "chain reversal regions" of the avian sarcoma/leukosis virus (ASLV) and ebolavirus fusion proteins: analogous residues are important, and a His residue unique to EnvA affects the pH dependence of ASLV entry. Journal of virology. 2010;84(11): 5687-94. PMID: 20335266
  • Dube D, Schornberg K, Shoemaker C, Delos S, Stantchev T, Clouse K, Broder C, White J. Cell adhesion-dependent membrane trafficking of a binding partner for the ebolavirus glycoprotein is a determinant of viral entry. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(38): 16637-42. PMID: 20817853 | PMCID: PMC2944755
  • Dube D, Brecher M, Delos S, Rose S, Park E, Schornberg K, Kuhn J, White J. The primed ebolavirus glycoprotein (19-kilodalton GP1,2): sequence and residues critical for host cell binding. Journal of virology. 2009;83(7): 2883-91. PMID: 19144707 | PMCID: PMC2655554
  • Melder D, Yin X, Delos S, Federspiel M. A charged second-site mutation in the fusion peptide rescues replication of a mutant avian sarcoma and leukosis virus lacking critical cysteine residues flanking the internal fusion domain. Journal of virology. 2009;83(17): 8575-86. PMID: 19515762 | PMCID: PMC2738199
  • Mire C, Dube D, Delos S, White J, Whitt M. Glycoprotein-dependent acidification of vesicular stomatitis virus enhances release of matrix protein. Journal of virology. 2009;83(23): 12139-50. PMID: 19776119 | PMCID: PMC2786704
  • Schornberg K, Shoemaker C, Dube D, Abshire M, Delos S, Bouton A, White J. Alpha5beta1-integrin controls ebolavirus entry by regulating endosomal cathepsins. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(19): 8003-8. PMID: 19416892 | PMCID: PMC2683081
  • Dube D, Schornberg K, Stantchev T, Bonaparte M, Delos S, Bouton A, Broder C, White J. Cell adhesion promotes Ebola virus envelope glycoprotein-mediated binding and infection. Journal of virology. 2008;82(14): 7238-42. PMID: 18448524 | PMCID: PMC2446962
  • White J, Delos S, Brecher M, Schornberg K. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Critical reviews in biochemistry and molecular biology. 2008;43(3): 189-219. PMID: 18568847 | PMCID: PMC2649671