HPV is a cargo for the COPI sorting complex during virus entry.

During entry, human papillomavirus (HPV) traffics from the cell surface to the endosome and then to the trans-Golgi network (TGN) and Golgi apparatus. HPV must transit across the TGN/Golgi and exit these compartments to reach the nucleus to cause infection, although how these steps are accomplished is unclear. Combining cellular fractionation, unbiased proteomics, and gene knockdown strategies, we identified the coat protein complex I (COPI), a highly conserved protein complex that facilitates retrograde trafficking of cellular cargos, as a host factor required for HPV infection.

p120 catenin recruits HPV to γ-secretase to promote virus infection.

During internalization and trafficking, human papillomavirus (HPV) moves from the cell surface to the endosome where the transmembrane protease γ-secretase promotes insertion of the viral L2 capsid protein into the endosome membrane. Protrusion of L2 through the endosome membrane into the cytosol allows the recruitment of cytosolic host factors that target the virus to the Golgi en route for productive infection. How endosome-localized HPV is delivered to γ-secretase, a decisive infection step, is unclear.

How non-enveloped viruses hijack host machineries to cause infection.

Viruses must navigate the complex endomembranous network of the host cell to cause infection. In the case of a non-enveloped virus that lacks a surrounding lipid bilayer, endocytic uptake from the plasma membrane is not sufficient to cause infection. Instead, the virus must travel within organelle membranes to reach a specific cellular destination that supports exposure or arrival of the virus to the cytosol.