The roles of cell proteins that interact with Human papillomavirus during virus entry

Human papillomaviruses (HPVs) are non-enveloped, double-stranded DNA viruses responsible for ~5% of human cancer. HPV virion contains the major capsid protein, L1 and the minor capsid protein, L2. L2 is essential for trafficking of the viral genome to the nucleus where viral gene expression and DNA replication occur. Upon virus internalization, the virus particle reaches the endosome where the low pH induces partial capsid disassembly. The cellular transmembrane protease, γ-secretase, deploys chaperone activity to promote the insertion of the C-terminus of L2 into the endosome membrane and then into the cytoplasm. Membrane insertion allows L2 to protrude into the cytosol and recruits cytosolic trafficking factors, such as the retromer sorting complex that delivers the virus to the trans-Golgi network (TGN). When the virus arrives TGN/Golgi, the cytoplasmic segment of L2 binds directly to the coat protein complex I (COPI) to promote HPV trafficking through the TGN and Golgi stacks. In this talk, I will describe the roles of COPI during virus entry and share new insights into retromer-mediated retrograde trafficking in uninfected cells.