@article{fdi:010094385, title = {{S}phingomyelins in mosquito saliva reconfigure skin lipidome to promote viral protein levels and enhance transmission of flaviviruses}, author = {{M}edkour, {H}. and {P}ruvost, {L}auryne and {M}iot, {E}. {F}. and {G}ong, {X}. {Q}. and {V}aissayre, {V}irginie and {T}avadia, {M}ihra and {B}outinaud, {P}ascal and {R}evel, {J}. and {H}itakarun, {A}. and {S}ornjai, {W}. and {S}mith, {D}. {R}. and {N}isole, {S}. and {H}oen, {E}. {N}. {T}. and {B}ertrand-{M}ichel, {J}. and {M}iss{\'e}, {D}oroth{\'e}e and {M}arti, {G}. and {P}ompon, {J}ulien}, editor = {}, language = {{ENG}}, abstract = {{M}any flaviviruses with high pandemic potential are transmitted through mosquito bites. {W}hile mosquito saliva is essential for transmission and represents a promising pan-flaviviral target, there is a dearth of knowledge on salivary metabolic transmission enhancers. {H}ere, 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. {L}ipids within internalized mosquito {EV}s enhance infection in fibroblast and immune human primary cells for multiple flaviviruses. {M}osquito {EV} lipids selectively increase viral translation by inhibiting infection-induced endoplasmic reticulum ({ER})-associated degradation of viral proteins. {I}nfection enhancement solely results from the sphingomyelins within salivary mosquito {EV}s that augment human cell sphingomyelin concentration. {F}inally, {EV}-lipid co-inoculation exacerbates disease severity in vivo in mouse transmission assays. {B}y 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.}, keywords = {}, booktitle = {}, journal = {{C}ell {M}etabolism}, volume = {37}, numero = {7}, pages = {[26 ]}, ISSN = {1550-4131}, year = {2025}, DOI = {10.1016/j.cmet.2025.05.015}, URL = {https://www.documentation.ird.fr/hor/fdi:010094385}, }