Abstract
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. This is achieved by viral penetration across a host endomembrane, ultimately enabling entry of the virus into the nucleus to initiate infection. In this review, we discuss the entry mechanisms of three distinct non-enveloped DNA viruses-adenovirus (AdV), human papillomavirus (HPV), and polyomavirus (PyV)-highlighting how each exploit different intracellular transport machineries and membrane penetration apparatus associated with the endosome, Golgi, and endoplasmic reticulum (ER) membrane systems to infect a host cell. These processes not only illuminate a highly-coordinated interplay between non-enveloped viruses and their host, but may provide new strategies to combat non-enveloped virus-induced diseases.