Concepts of papillomavirus entry into host cells

Abstract

Papillomaviruses enter basal cells of stratified epithelia. Assembly of new virions occurs in infected cells during terminal differentiation. This unique biology is reflected in the mechanism of entry. Extracellularly, the interaction of nonenveloped capsids with several host cell proteins, after binding, results in discrete conformational changes. Asynchronous internalization occurs over several hours by an endocytic mechanism related to, but distinct from macropinocytosis. Intracellular trafficking leads virions through the endosomal system, and from late endosomes to the trans-Golgi-network, before nuclear delivery. Here, we discuss the existing data with the aim to synthesize an integrated model of the stepwise process of entry, thereby highlighting key open questions. Additionally, we relate data from experiments with cultured cells to in vivo results.

Figure 1. Schematic depiction of PV entry

Depicted are certain steps of PV entry into host cells. The initial interaction with cellular receptors and structural modifications on the cell surface or ECM/basement membrane are enlarged for a better view. Inidcated is also the uptake by a novel, ligand-activated endocytic mechanism where actin polymerization assists in vesicle scission from the plasma membrane. After internalization, the structurally modified PV particles are delivered to an early endosomal compartment, i.e. early endosome or macropinosome-like endosome. Delivery of a subviral complex consisting of L2 and the vDNA to the TGN occurs after separation of most of the L1 capsomers through Rab7b/Rab9- and/or retromer-mediated vesicular trafficking. After membrane penetration and nuclear import the subviral complex locates to ND10 in the nucleus. Indicated is the need for acidification of endosomal organelles by the yellow shading of organelles.