Possible role for the adaptor protein complexes in sorting of human papillomavirus

Abstract

Human papillomaviruses (HPVs) infect genital and mucosal epithelium and persistent infection with high‐risk strains like HPV16 are associated with cervical, anogenital, and nasopharyngeal cancers. HPV16 particles consist of two structural proteins: the major capsid protein L1 and the minor capsid protein L2. In a previous yeast two hybrid screen using L2 as bait, we identified a potential interaction with a truncated μ chain (μ2) of the adaptor protein complex‐2 (AP2). The AP complex family directs vesicular sorting of cargo via interactions between the AP complex μ subunits and YxxΦ motifs within the cytoplasmic tails of transmembrane receptors. Interestingly L2 contains a number of YxxΦ motifs with variable conservation among different HPV types. The goal of this project is to determine which AP complexes L2 interacts with, how these interactions occur, and the functions of these interactions during infection. Yeast two‐hybrid screens indicate that full‐length L2 interacts with all AP complex μ chains but smaller L2‐YxxΦ peptides have preference for specific μ chains. Infections with YxxΦ‐mutant viruses show decreased infectivity, strongly supporting a role for AP complexes in infection. siRNA single knockdowns of AP complex μ chains show varying effects on infectivity. Current work seeks to understand the nature of these defects and to assess specific roles for L2‐AP complex interactions during infection.Support for this research comes from the Undergraduate Biology Research Program (U. of Arizona UBRP) and the American Cancer Society Research Scholar Grant RSG‐117469.