Toll-9 elicits antiviral immunity against Drosophila C virus.

UNLABELLED

The Toll pathway plays a pivotal role in innate immune responses against pathogens. The evolutionarily conserved pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), play a crucial role in recognition of pathogen-associated molecular patterns (PAMPs). The genome encodes nine Toll receptors that are orthologous to mammalian TLRs. While mammalian TLRs directly recognize PAMPs, most Tolls recognize the proteolytically cleaved ligand Spätzle to activate downstream signaling cascades. In this study, we demonstrated that Toll-9 is crucial for antiviral immunity against Drosophila C virus (DCV), a natural pathogen of . A transposable element insertion in the gene renders the flies more susceptible to DCV. The stable expression of Toll-9 in S2 cells results in increased induction and reduced AKT phosphorylation, collectively establishing an antiviral state that inhibits DCV replication. Toll-9 localizes to endosomes, where it binds viral double-stranded RNA (dsRNA), highlighting its role in detecting viral replication intermediates. Together, these findings identify Toll-9 as a key player in antiviral immunity against DCV infection, acting through its ability to recognize dsRNA and drive expression, along with other AKT-mediated antiviral responses.

IMPORTANCE

Insects rely on innate immunity and RNA interference (RNAi) to combat viral infections. Our study underscores the pivotal role of Toll-9 in antiviral immunity, aligning with findings in , where Toll-9 activation upregulates the RNAi component . We demonstrate that Toll-9 functions as a pattern recognition receptor (PRR) for double-stranded RNA (dsRNA) during Drosophila C virus (DCV) infection, akin to mammalian Toll-like receptors (TLRs). Toll-9 activation during DCV infection leads to the upregulation of and and dephosphorylation of AKT. This study also reveals that Toll-9 localizes in endosomal compartments where it interacts with dsRNA. These insights enhance our understanding of innate immune mechanisms, reflecting the evolutionary conservation of immune responses across diverse species and providing impetus for further research into the conserved roles of TLRs across the animal kingdom.