PROJECT SUMMARY / ABSTRACTThroughout the course of coevolution within their host organisms viruses have evolved tobecome masters of the cell- manipulating and exploiting cellular signaling transport andtrafficking pathways. Studies of basic virology offer the prospect of illuminating cellular biologythrough the lens of a natural cell biologist often (and historically) unveiling new aspects of cellularform and function. Here we propose work to elucidate the membrane spanning and subcellulartrafficking mechanisms used by the human papillomavirus (HPV) L2 capsid protein during thecourse 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 membranecurvature and tension ion flux cellular gamma secretase and specific L2 elements (amphipathichelix transmembrane domain C-terminal cell penetration peptide) in L2 membrane spanning. Wehave 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 inhibitorymechanisms of the peptide and unveil the role(s) of the cellular SNX-BAR family of sorting nexinproteins on L2 membrane spanning and retrograde trafficking of virus. Combined this work willunveil new insight into cellular biology of protein-membrane interactions protein transport acrossmembranes and vesicular trafficking.