The main focus of the White Laboratory is on virus entry into host cells. A particular interest is on the membrane fusion event that introduces the genomes of enveloped viruses (such as HIV and influenza) into host cells.


Virus Entry Into Cells
: Our past work has focused on how the fusion proteins of enveloped viruses elicit the critical genome-releasing membrane fusion event that must occur with a host cell membrane to initiate an infection. Our studies, particularly with the hemagglutinin of influenza virus and with the Env glycoproteins of retroviruses, have aided in the development of a model for how such 'class I' viral membrane fusion proteins function. Importantly, it now appears that a very similar mechanism is used by all (i.e., class I, II and III) viral membrane fusion proteins, and that steps in this universal viral fusion cascade can be targeted for anti-viral intervention.

Our current work is focused on characterizing novel viral entry pathways and fusion triggers, and on identifying small molecules and antibodies that can inhibit infection by blocking virus binding to, or fusion with, host cells. Our most current efforts are directed at elucidating how filoviruses, such as ebolavirus, enter cells. (In our laboratory we study filovirus entry solely with pseudovirions and viral like particles expressing the viral entry glycoprotein.) We are interested in all stages of filovirus entry and were drawn to studies of filoviruses due to several novel features that they present in terms of the cell biology of virus entry. In particular, filoviruses are unusually-shaped (long and filamentous) compared to most enveloped viruses. And, ebolavirus uses a novel means (cleavage by endosomal cathepsins) to prime, and an apparently novel means to trigger, its glycoprotein for fusion. We have also recently participated in screens that have identified small molecule filovirus inhibitors. Our studies should reveal new principles about virus entry into cells and will aid in the development of therapeutics to treat filovirus infections.