Intercampus Collaboration Yields a Successful Multi-PI R01
Many viruses are cloaked with an envelope derived from the host cell. To deliver the genome of the virus into the cell, viruses encode dedicated glycoproteins (fusion proteins) that are embedded in the envelope and which mediate the membrane fusion process. These fusion proteins come in three basic classes, with “class I” being found in such important viruses as influenza, HIV and paramyxoviruses. In these cases, it is well known that during virus entry a critical peptide is flipped out of the glycoprotein following proteolytic cleavage—to produce a so-called “external” fusion peptide. However, within class I there are a subset of glycoproteins that have “internal” fusion peptides that are much less well understood. Such viruses include some of great biomedical importance: SARS-coronavirus, Ebola virus and Lassa virus.
Beginning with a collaboration between a virologist (Whittaker) and an engineer (Daniel), key determinants of SARS-coronavirus were determined using single particle techniques, which were then integrated with biophysical techniques (Freed and Eliezer) to yield a successful multi-PI R01 between the Ithaca and NYC campuses. The group believes that common themes exist between SARS-coronavirus, Ebola virus and Lassa virus beyond the level of an internal fusion peptide. There are common structural properties of the fusion peptide itself, common endosomal trafficking routes, and common receptor localizations that are all ultimately tied to the use of calcium ions as a fusion trigger.
The initial group has now been joined by a virologist with an additional focus on membrane fusion (Aguilar-Carreno) to decipher the entry and fusion pathways of Ebola virus and Lassa virus using the same biophysical foundation. The group believes that an understanding of these atypical fusion peptides will provide mechanistic insight into immunotherapies, vaccines and drugs for these viruses, which are currently among the highest profile public health concerns.