Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle

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Vial, Thomas | Tan, Wei-Lian | Deharo, Eric | Missé, Dorothée | Marti, Guillaume | Pompon, Julien

Edité par CCSD ; National Academy of Sciences -

International audience. Dengue virus (DENV) subdues cell membranes for its cellular cycleby reconfiguring phospholipids in humans and mosquitoes. Here,we determined how and why DENV reconfigures phospholipids inthe mosquito vector. By inhibiting and activating the de novophospholipid biosynthesis, we demonstrated the antiviral impactof de novo–produced phospholipids. In line with the virus hijackinglipids for its benefit, metabolomics analyses indicated thatDENV actively inhibited the de novo phospholipid pathway andinstead triggered phospholipid remodeling. We demonstrated theearly induction of remodeling during infection by using isotopetracing in mosquito cells. We then confirmed in mosquitoes theantiviral impact of de novo phospholipids by supplementing infectiousblood meals with a de novo phospholipid precursor. Eventually,we determined that phospholipid reconfiguration was requiredfor viral genome replication but not for the other steps of the viruscellular cycle. Overall, we now propose that DENV reconfiguresphospholipids through the remodeling cycle to modify the endomembraneand facilitate formation of the replication complex. Furthermore,our study identified de novo phospholipid precursor as ablood determinant of DENV human-to-mosquito transmission.

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