Vial Thomas, Tan W. L., Deharo Eric, Missé Dorothée, Marti G., Pompon Julien. (2020). Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle. Proceedings of the National Academy of Sciences of the United States of America, 117 (44), p. 27627-27636. ISSN 0027-8424.
Titre du document
Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle
Vial Thomas, Tan W. L., Deharo Eric, Missé Dorothée, Marti G., Pompon Julien
Source
Proceedings of the National Academy of Sciences of the United States of America, 2020,
117 (44), p. 27627-27636 ISSN 0027-8424
Dengue virus (DENV) subdues cell membranes for its cellular cycle by reconfiguring phospholipids in humans and mosquitoes. Here, we determined how and why DENV reconfigures phospholipids in the mosquito vector. By inhibiting and activating the de novo phospholipid biosynthesis, we demonstrated the antiviral impact of de novo-produced phospholipids. In line with the virus hijacking lipids for its benefit, metabolomics analyses indicated that DENV actively inhibited the de novo phospholipid pathway and instead triggered phospholipid remodeling. We demonstrated the early induction of remodeling during infection by using isotope tracing in mosquito cells. We then confirmed in mosquitoes the antiviral impact of de novo phospholipids by supplementing infectious blood meals with a de novo phospholipid precursor. Eventually, we determined that phospholipid reconfiguration was required for viral genome replication but not for the other steps of the virus cellular cycle. Overall, we now propose that DENV reconfigures phospholipids through the remodeling cycle to modify the endomembrane and facilitate formation of the replication complex. Furthermore, our study identified de novo phospholipid precursor as a blood determinant of DENV human-to-mosquito transmission.
