Virus Recognition by Toll-7 Activates Antiviral Autophagy in Drosophila

Abstract

Innate immunity is highly conserved and relies on pattern recognition receptors (PRRs) such as Toll-like receptors (identified through their homology to Drosophila Toll) for pathogen recognition. While Drosophila Toll is vital for immune recognition and defense, roles for the other eight Drosophila Tolls in immunity have remained elusive. Here we have shown that Toll-7 is a PRR both in vitro and in adult flies; loss of Toll-7 led to increased Vesicular Stomatitis virus (VSV) replication and mortality. Toll-7, along with additional uncharacterized Drosophila Tolls, were transcriptionally induced by VSV infection. Furthermore, Toll-7 interacted with VSV at the plasma membrane and induced antiviral autophagy independently of the canonical Toll signaling pathway. These data uncover an evolutionarily conserved role for a second Drosophila Toll receptor that links viral recognition to autophagy and defense, and suggest that other Drosophila Tolls may restrict specific as yet untested pathogens, perhaps via non-canonical signaling pathways.

Antiviral immunity in marine molluscs

“…Other pathogen sensors (such as TLR3, TLR4, TLR7, TLR8 and NOD2) are also known to induce autophagy upon binding with their specific ligand, via a MyD88 independent pathway (reviewed by Richetta & Faure, 2013). Autophagy is also an antiviral mechanism utilized by arthropods (Nakamoto et al, 2012). In Drosophila, Toll-7 recognizes vesicular stomatitis virus (VSV) at the plasma membrane and induces antiviral autophagy via an NF-kB-independent pathway (Nakamoto et al, 2012).…”

“…Autophagy is also an antiviral mechanism utilized by arthropods (Nakamoto et al, 2012). In Drosophila, Toll-7 recognizes vesicular stomatitis virus (VSV) at the plasma membrane and induces antiviral autophagy via an NF-kB-independent pathway (Nakamoto et al, 2012). …”

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

“…RNAi in Drosophila cells is robust, and conserved immune biology with humans has been demonstrated (e.g., Toll) (Lemaitre et al 1996), suggesting that we can use Drosophila to probe both insect and human antiviral factors (Cherry 2005;Hao et al 2008;Sabin et al 2009;Sessions et al 2009;Moser et al 2010;Rose et al 2011). Furthermore, Drosophila has been used as a model to study arboviral infection, including RVFV (Sabin et al 2009;Sessions et al 2009;Filone et al 2010;Moser et al 2010;Rose et al 2011;Nakamoto et al 2012). …”

Variable immune molecules in invertebrates

“…In Drosophila, Spätzle is a ligand for Toll during both embryogenesis and AMP induction but the up-stream events that finally lead to cleavage of pro-Spätzle into Spätzle differ (Morisato and Anderson, 1995; Lemaitre et al, 1996). However, in one recent study the direct binding of an arbovirus to the Drosophila Toll-7 receptor was demonstrated (Nakamoto et al, 2012). Caution must therefore be exercised when assigning a function for newly discovered TLRs in different phyla.…”