The human papillomavirus ( HPV ) L 2 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 ( SNX 17) as a strong interacting partner of HPV L 2. This interaction occurs through a highly conserved SNX 17 consensus binding motif, which is present in the majority of HPV L 2 proteins analysed. Using mutants of L 2 defective for SNX 17 interaction, or siRNA ablation of SNX 17 expression, we demonstrate that the interaction between L 2 and SNX 17 is essential for viral infection. Furthermore, loss of the L 2– SNX 17 interaction results in enhanced turnover of the L 2 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 SNX 17 transit much more rapidly to the lysosomal compartment. These results demonstrate that the L 2– SNX 17 interaction is essential for viral infection and facilitates the escape of the L 2– DNA complex from the late endosomal/lysosomal compartments.

Human Papillomavirus L2 Facilitates Viral Escape from Late Endosomes via Sorting Nexin 17