Furin - a key to virus replication in mosquitoes

Dr. Kornelia Hardes:

        »Furin-like proteins enable viruses to replicate in mosquitoes and offer new approaches for future antiviral strategies.«

Mosquitoes transmit a variety of viruses (so-called arboviruses) that infect millions of people worldwide each year. To replicate within mosquitoes, these viruses rely on specific proteins produced by mosquito cells. One of them is the protein Furin - a kind of molecular scissors - that cleaves viral proteins and thus enables virus replication. While Furin is already relatively well studied in mammals, little is known about comparable proteins in mosquitoes.

In this study, furin-like genes in the Asian tiger mosquito Aedes albopictus were investigated. Two genes (FLP1 and FLP2) were identified, whose genetic blueprint (mRNA) was detectable in all developmental stages - from larva to adult mosquito - as well as in two mosquito cell lines. It was also tested whether synthetic furin inhibitors are taken up by mosquito cells and whole mosquitoes and whether they prevent the replication of the model virus Semliki Forest Virus.

A labeled inhibitor was well taken up by cell cultures, young larvae, and adult females. Three other inhibitors reduced the spread of the virus significantly in cell culture. In the living organism, however, the tested inhibitor showed only a small antiviral effect.

The results show: furin-like proteins are important factors for virus replication in mosquitoes and thus potential targets for new antiviral strategies. At the same time, it becomes clear that an inhibitor that is hardly absorbed beyond the gut hardly realize its promising laboratory results in the whole organism.