PROJECT SUMMARY / ABSTRACT
Throughout the course of coevolution within their host organisms, viruses have evolved to
become masters of the cell- manipulating and exploiting cellular signaling, transport, and
trafficking pathways. Studies of basic virology offer the prospect of illuminating cellular biology
through the lens of a natural cell biologist, often (and historically) unveiling new aspects of cellular
form and function. Here we propose work to elucidate the membrane spanning and subcellular
trafficking mechanisms used by the human papillomavirus (HPV) L2 capsid protein during the
course of early infection within endo/lysosomal, retrograde transport, and Golgi compartments.
Here we will work to understand the role(s) of the local membrane microenvironment, membrane
curvature and tension, ion flux, cellular gamma secretase, and specific L2 elements (amphipathic
helix, transmembrane domain, C-terminal cell penetration peptide) in L2 membrane spanning. We
have also recently discovered that a small peptide derived from cellular sorting nexin 1 (SNX1)
potently blocks the retrograde trafficking of HPV, and we propose work to elucidate the inhibitory
mechanisms of the peptide and unveil the role(s) of the cellular SNX-BAR family of sorting nexin
proteins on L2 membrane spanning and retrograde trafficking of virus. Combined, this work will
unveil new insight into cellular biology of protein-membrane interactions, protein transport across
membranes, and vesicular trafficking.
