Effects of Manipulating Fibroblast Growth Factor Expression on Sindbis Virus Replication In Vitro and in Aedes aegypti Mosquitoes

Abstract

Fibroblast growth factors (FGFs) are conserved among vertebrate and invertebrate animals and function in cell proliferation, cell differentiation, tissue repair, and embryonic development. A viral fibroblast growth factor (vFGF) homolog encoded by baculoviruses, a group of insect viruses, is involved in escape of baculoviruses from the insect midgut by stimulating basal lamina remodeling. This led us to investigate whether cellular FGF is involved in the escape of an arbovirus from mosquito midgut. In this study, the effects of manipulating FGF expression on Sindbis virus (SINV) replication and escape from the midgut of the mosquito vector Aedes aegypti were examined. RNAi-mediated silencing of either Ae. aegypti FGF (AeFGF) or FGF receptor (AeFGFR) expression reduced SINV replication following oral infection of Ae. aegypti mosquitoes. However, overexpression of baculovirus vFGF using recombinant SINV constructs had no effect on replication of these viruses in cultured mosquito or vertebrate cells, or in orally infected Ae. aegypti mosquitoes. We conclude that reducing FGF signaling decreases the ability of SINV to replicate in mosquitoes, but that overexpression of vFGF has no effect, possibly because endogenous FGF levels are already sufficient for optimal virus replication. These results support the hypothesis that FGF signaling, possibly by inducing remodeling of midgut basal lamina, is involved in arbovirus midgut escape following virus acquisition from a blood meal.