The Human Papillomavirus (HPV) L2 capsid protein plays an essential role during the early stages of viral infection, but the molecular mechanisms underlying its mode of action remain obscure. Using a proteomic approach we have identified the adaptor protein, Sorting Nexin 17 (SNX17) as a strong interacting partner of HPV L2. This interaction occurs through a highly conserved SNX17 consensus binding motif, which is present in the majority of HPV L2 proteins analysed. Using mutants of L2 defective for SNX17 interaction, or siRNA ablation of SNX17 expression we demonstrate that the interaction between L2 and SNX17 is essential for viral infection. Furthermore, loss of the L2-SNX17 interaction results in enhanced turnover of the L2 protein and decreased stability of the viral capsids, and concomitantly there is a dramatic decrease in the efficiency with which viral genomes transit to the nucleus. Indeed, using a range of endosomal and lysosomal markers we show that capsids defective in their capacity to bind SNX17 transit much more rapidly to the lysosomal compartment. These results demonstrate that the L2-SNX17 interaction is essential for viral infection and facilitates the escape of the L2-DNA complex from the late endosomal/lysosomal compartments.

This work focuses on the photocatalytic performances and antibacterial activity of TiO 2 and Au/TiO 2 nanosystems. While the former are obtained by a sol-gel route, the latter are synthesized by an innovative hybrid RF-sputtering/sol-gel approach, followed by ex situ annealing in air up to 600 • C. Important information on nanoparticle size, shape and distribution is obtained by the combined use of glancing incidence x-ray diffraction (GIXRD) and field emission-scanning electron microscopy (FE-SEM). Subsequently, the photocatalytic performances of the obtained nanosystems in the decomposition of the azo-dye Plasmocorinth B and their antibacterial activity in the elimination of Bacillus subtilis are illustrated and discussed in comparison with films obtained from standard Degussa P25 powders. The obtained results show a significant dependence of the functional performances on the system's compositional, structural and morphological properties. In particular, the dispersion of gold nanoparticles on the TiO 2 matrix has a beneficial influence on the azo-dye photodegradation, whereas the antimicrobial activity of Au/TiO 2 films is retarded with respect to pure TiO 2 .

The human papillomavirus (HPV) E6 oncoprotein is fundamental to the ability of these viruses to induce human malignancy. A defining characteristic of the HPV E6 oncoproteins found in cancer‐causing HPV types is the presence of a PDZ binding motif at their extreme C‐terminus. Through this motif, E6 is able to interact with a large number of cellular proteins that contain PDZ domains. Many of these cellular proteins are involved in regulation of processes associated with the control of cell attachment, cell proliferation, cell polarity and cell signaling. How E6 targets multiple proteins containing the same recognition domain is still an open question. In this review, we highlight aspects of E6 function and biology that help to answer this question, and thereby provide insight into the role of these substrates during development of HPV‐induced malignancy.

Previous studies have demonstrated an interaction between sorting nexin 17 and the L2 capsid proteins from a variety of papillomavirus types. This interaction is required for late endosomal trafficking of the L2 protein and entry of the L2/DNA complex into the nucleus during infection. Here we show an interaction between papillomavirus L2 proteins and the related PX-FERM family member sorting nexin 27 (SNX27), which is mediated in part by a novel interaction between the PDZ domain of SNX27 and sequences in a central portion of L2. The interaction is direct and, unlike that with SNX17, is variable in strength depending on the papillomavirus type. We show that small interfering RNA (siRNA)-mediated knockdown of SNX27 alone leads to a marginal reduction in the efficiency of viral infection but that double knockdown of both sorting nexins results in a striking reduction in infection, greater than that observed for the knockdown of either sorting nexin alone. These results suggest that the HPV L2 proteins can interact through distinct mechanisms with multiple components of the cellular cargo-sorting machinery. IMPORTANCEThe trafficking of papillomaviruses to the host cell nucleus during their natural infectious life cycle is an incompletely understood process. Studies have suggested that the virus minor capsid protein L2 can interact with the endosomal recycling pathway, in part by association with sorting nexin 17, to ensure that virus DNA bound to L2 is recycled through the trans-Golgi network rather than back to the plasma membrane. In this study, we characterize the interaction between L2 and a second sorting nexin, SNX27, which is also part of the retromer complex. The study furthers our understanding of papillomavirus infection dynamics and provides potential tools for the further dissection of endosomal structure and function.T he entry of papillomaviruses (PVs) into host cells involves a series of coordinated steps whereby virus particles attach to cell surface receptors and are internalized into endocytic vesicles. This allows the virus capsid proteins, tethered to the viral genome, to interact with cellular protein complexes within endosomes, which are exploited to allow virion disassembly, followed by the transport of L2 and the viral genome to the nucleus and their entry into the nucleus, for subsequent expression of viral transcripts. The precise details of the first step in this cascade of events remain, to a degree, controversial, although it seems that different papillomavirus types exploit different mechanisms to gain entry to the cell (1-3). Subsequent steps during viral infection may be common to all papillomavirus types and, although incompletely understood, involve virion disassembly during endosome acidification and subsequent separation of L1 and L2. While the majority of L1 is sorted into lysosomes, L2, tethered to the viral genome, is transported through the trans-Golgi network (4) and finally enters the nucleus during mitosis (5), when the nuclear membrane is dissolved, where it loca...