University of Virginia Health System

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.

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http://www.people.virginia.edu/~jw7g