Judith M. White, PhD
Graduate School: Harvard University
Primary Appointment: Professor, Cell Biology
Virus Entry into Cells, Virus-Cell Fusion, Entry Inhibitors
Email Address: firstname.lastname@example.org
The White Laboratory studies virus entry into host cells. Our past work has focused on mechanisms by which the fusion proteins of enveloped viruses (e.g. the influenza hemagglutinin and retroviral Env proteins) mediate the critical process of virus-cell fusion, which introduces the viral genetic material into cells and initiates the infection cycle. Our work has uncovered key steps in the process of virus fusion with host cell membranes: the conformational changes that convert a viral fusion protein to a trimeric “prehairpin” state in which its fusion peptide (or loop) is firmly tethered in the host cell bilayer and the additional “fold-back” steps that form the final “trimer-of-hairpins” that mediates the hemifusion and fusion pore opening stages of fusion.
We have also studied triggers that activate different viral fusion proteins (e.g. low endosomal pH for influenza virus, interaction with host cell receptors for HIV, and engagement by host cell receptors followed by exposure to low pH for avian retroviruses.) We are currently studying how filoviruses, typified by the highly pathogenic ebolavirus, enter and fuse with host cells. We are intrigued to study ebolavirus entry (which we do under BSL-2 conditions with pseudovirions and viral-like particles) for several reasons: Ebolavirus infects a wide variety of host cells, but its receptor is unknown. The virus is large and unusually shaped; it is not known how the virus is endocytosed and trafficked to its fusion site (a late endosomal compartment). And lastly, ebolavirus uses an apparently novel fusion-triggering mechanism. In addition to basic studies that address these unknown features of ebolavirus entry and fusion, we aim to identify inhibitors that block filovirus entry into host cells.
Xu G, Wei S, White JM, DeSimone DW. Identification and characterization of ADAM41, a novel ADAM metalloproteinase in Xenopus. Int J Dev Biol. 2012;56(5):333-9. doi: 10.1387/ijdb.113444gx.
White JM, Schornberg KL. A new player in the puzzle of filovirus entry. Nat Rev Microbiol. 2012 Apr 11;10(5):317-22. doi: 10.1038/nrmicro2764.
Wei S, Xu G, Bridges LC, Williams P, Nakayama T, Shah A, Grainger RM, White JM, DeSimone DW. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Dev Biol. 2012 Mar 1;363(1):147-54. doi: 10.1016/j.ydbio.2011.12.031. Epub 2011 Dec 28.
Brecher M, Schornberg KL, Delos SE, Fusco ML, Saphire EO, White JM. Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change. J Virol. 2012 Jan;86(1):364-72. doi: 10.1128/JVI.05708-11. Epub 2011 Oct 26.
Gregory SM, Harada E, Liang B, Delos SE, White JM, Tamm LK. Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11211-6. doi: 10.1073/pnas.1104760108. Epub 2011 Jun 20.
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