Multi-layered control of Galectin-8 mediated autophagy during adenovirus cell entry through a conserved PPxY motif in the viral capsid

• DOI: 10.1371/journal.ppat.1006217
• Publication Date: 2017-02-13T19:49:45Z
• Authors: Charlotte Montespan; Shauna A. Marvin; Sisley Austin; Andrew M. Burrage; Benoit Roger; Fabienne Rayne; Muriel Faure; Edward M. Campell; Carola Schneider; Rudolph Reimer; Kay Grünewald; Christopher M. Wi...; Harald Wodrich
• Keywords: Autophagosome; Lytic cycle

Cells employ active measures to restrict infection by pathogens, even prior responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture sequester deliver fragments their contents for lysosomal degradation. Adenoviruses, which breach endosome entry, escape fate penetrating into cytosol autophagosome sequestration of ruptured endosome. We show that virus damage recognized through Galectin-8 sequesters receptors NDP52 p62. further a conserved PPxY motif in viral lytic protein VI critical efficient evasion autophagic after endosomal lysis. Comparing wildtype with PPxY-mutant we depletion or suppression ATG5-/- MEFs rescues infectivity while NDP52, p62 has only minor effects. Furthermore viruses exploit machinery nuclear genome delivery control formation via cellular ubiquitin ligase Nedd4.2 resulting reduced antigenic presentation. Our data thus demonstrate short PPxY-peptide adenoviral capsid permits multi-layered processes during entry.