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

Wenbi Wu,A Lorena Passarelli,Cody A Simmons,Rollie J Clem,Jessica Moffitt

doi:10.3390/v12090943

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.

Highlights

Fibroblast growth factor (FGF) homologs are ubiquitous in metazoans and the Fibroblast growth factors (FGFs) signaling pathway is involved in a variety of processes such as angiogenesis, wound healing, and embryonic development [1]
In order to study the role of FGF signaling during viral infection in mosquitoes, we first tested whether levels of Aefgf mRNA were altered in mosquitoes that were given a blood meal containing or lacking Sindbis virus (SINV)
Insights into how baculoviruses escape the midgut barrier of their insect hosts have come from studies of the baculovirus-encoded vfgf gene

Summary

Introduction

Fibroblast growth factor (FGF) homologs are ubiquitous in metazoans and the FGF signaling pathway is involved in a variety of processes such as angiogenesis, wound healing, and embryonic development [1]. When released from cells, FGF binds to the FGF receptor (FGFR) and initiates signaling through Ras-MAPK and other pathways. In Drosophila, FGF and FGFR have been shown to play important roles in the development of the tracheal system during embryonic development and later in developing larvae [2]. One process that is known to be triggered by FGF signaling is remodeling of basal lamina [3], part of the extracellular matrix that is secreted by epithelial cells and is mainly composed of type IV collagen, laminin, nidogen, and perlecan proteoglycans.

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