Rupert Beale
University of Cambridge
UK
Title: Subversion of Autophagy by Viral LC3 Interacting Regions
Biography
Biography: Rupert Beale
Abstract
Autophagy can provide a cell with nutrients in time of starvation by engulfing cytoplasmic contents in a double membrane, targeting the autophagosome to a lysosome, and utilizing the resultant lipids and amino-acids for metabolism. This process has been adapted to form a critical component of cellular self-defence, with invading micro-organisms targeted for autophagy by adaptor proteins that can bind both to danger signals in the cytosol, and to the LC3 molecules that decorate the autophagosomal membrane (Boyle and Randow, 2013). Binding to LC3 typically takes place via a LIR (LC3 Interacting Region), a short motif comprising a hydrophobic beta-strand and surrounding acidic residues. We have discovered that influenza M2 contains a LIR at its C-terminal tail (Beale et al., 2014). This enables influenza to subvert autophagy, and promotes the formation of stable virions. M2 also has a LIR independent function to subvert autophagy, inhibiting fusion of autophagosomes with lysosomes (Gannage et al., 2009). We propose that influenza M2 targets autophagosomes to the plasma membrane to increase resources for budding, and present evidence that other enveloped viruses also encode LC3-interacting regions.
