Impact of ERK activation on fly survival and Wolbachia-mediated protection during virus infection

Abstract

Elevated levels of reactive oxygen species (ROS) provide protection against virus-induced mortality in Drosophila. In addition to contributing to oxidative stress, ROS are known to activate a number of signalling pathways including the extracellular signal-regulated kinases (ERK) signalling cascade. It was recently shown that ERK signalling is important for resistance against viral replication and invasion in cultured Drosophila cells and the gut epithelium of adult flies. Here, using a Drosophila loss-of-function ERK (rolled) mutant we demonstrated that ERK is important for fly survival during virus infection. ERK mutant flies subjected to Drosophila C virus (DCV) oral and systemic infection were more susceptible to virus-induced mortality as compared with wild-type flies. We have demonstrated experimentally that ERK activation is important for fly survival during oral and systemic virus infection. Given that elevated ROS correlates with Wolbachia-mediated antiviral protection, we also investigated the involvement of ERK in antiviral protection in flies infected by Wolbachia. The results indicate that ERK activation is increased in the presence of Wolbachia but this does not appear to influence Wolbachia-mediated antiviral protection, at least during systemic infection.

Immune priming and clearance of orally acquired RNA viruses in Drosophila

“…Less than 10% mortality was observed in w 1118 flies 15 days after oral infection with DCV, CrPV and FHV ( Fig. 1d-f), consistent with previous studies 12,23,24 . In contrast, 20-50% mortality was observed for Ago-2 -/and Dcr-2 -/flies.…”

Innate and intrinsic antiviral immunity in Drosophila

“…Restriction factors represent a third topic worthy of interest, and one can predict that the structural and functional characterization of the products of the genes that have been identified will provide important insight. Finally, the mechanism by which the intracellular endosymbiont bacterium Wolbachia potently interferes with viral infection in flies represent another exciting question [145, 146]. …”

Antiviral Immune Response and the Route of Infection in Drosophila melanogaster

“…Drosophila are naturally exposed to pathogens while foraging on decaying fruit, with the most common route of access of pathogens being oral infection in the digestive system and/or contact with the tracheal system. Different experimental methods for oral infection in Drosophila have been described: exposing larvae with virus particles from the beginning of the first instar (Jousset and Plus, 1975, Lautie-Harivel, 1992, Gomariz-Zilber et al, 1998, Gomariz-Zilber et al, 1995, Gomariz-Zilber and Thomas-Orillard, 1993, Thomas-Orillard, 1988, Thomas-Orillard, 1984, Vale and Jardine, 2015, or by feeding adult flies with a mix of food and pathogen solution (Jousset and Plus, 1975, Gomariz-Zilber et al, 1995, Ferreira et al, 2014, Wong et al, 2016, Gupta et al, 2017a, Xu et al, 2013.…”