Sphingomyelins in mosquito saliva reconfigure skin lipidome to promote viral protein levels and enhance transmission of flaviviruses
Issued Date
2025-01-01
Resource Type
ISSN
15504131
eISSN
19327420
Scopus ID
2-s2.0-105008575300
Journal Title
Cell Metabolism
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell Metabolism (2025)
Suggested Citation
Medkour H., Pruvost L., Miot E.F., Gong X., Vaissayre V., Tavadia M., Boutinaud P., Revel J., Hitakarun A., Sornjai W., Zoladek J., Smith D.R., Nisole S., Nolte-‘t Hoen E., Bertrand-Michel J., Missé D., Marti G., Pompon J. Sphingomyelins in mosquito saliva reconfigure skin lipidome to promote viral protein levels and enhance transmission of flaviviruses. Cell Metabolism (2025). doi:10.1016/j.cmet.2025.05.015 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110944
Title
Sphingomyelins in mosquito saliva reconfigure skin lipidome to promote viral protein levels and enhance transmission of flaviviruses
Author's Affiliation
Université de Toulouse
Faculteit Diergeneeskunde
Maladies Infectieuses et Vecteurs : Écologie, Génétique, Évolution et Contrôle
Institut des Maladies Métaboliques et Cardiovasculaires
Institute of Molecular Biosciences, Mahidol University
Diversité, Adaptation et Développement des Plantes
Institut de Recherche en Infectiologie de Montpellier
National Infrastructure of Metabolomics and Fluxomics
Faculteit Diergeneeskunde
Maladies Infectieuses et Vecteurs : Écologie, Génétique, Évolution et Contrôle
Institut des Maladies Métaboliques et Cardiovasculaires
Institute of Molecular Biosciences, Mahidol University
Diversité, Adaptation et Développement des Plantes
Institut de Recherche en Infectiologie de Montpellier
National Infrastructure of Metabolomics and Fluxomics
Corresponding Author(s)
Other Contributor(s)
Abstract
Many flaviviruses with high pandemic potential are transmitted through mosquito bites. While mosquito saliva is essential for transmission and represents a promising pan-flaviviral target, there is a dearth of knowledge on salivary metabolic transmission enhancers. Here, we show that extracellular vesicle (EV)-derived sphingomyelins in mosquito saliva reconfigure the human cell lipidome to increase viral protein levels, boosting skin infection and enhancing transmission for flaviviruses. Lipids within internalized mosquito EVs enhance infection in fibroblast and immune human primary cells for multiple flaviviruses. Mosquito EV lipids selectively increase viral translation by inhibiting infection-induced endoplasmic reticulum (ER)-associated degradation of viral proteins. Infection enhancement solely results from the sphingomyelins within salivary mosquito EVs that augment human cell sphingomyelin concentration. Finally, EV-lipid co-inoculation exacerbates disease severity in vivo in mouse transmission assays. By discovering and elucidating how metabolic components of mosquito saliva promote transmission of flaviviruses, our study unveils lipids as a new category of targets against vectored transmission.