@article{fdi:010087618, title = {{T}he anti-immune dengue subgenomic flaviviral {RNA} is present in vesicles in mosquito saliva and is associated with increased infectivity}, author = {{Y}eh, {S}. {C}. and {S}trilets, {T}. and {T}an, {W}. {L}. and {C}astillo, {D}. and {M}edkour, {H}ac{\`e}ne and {R}ey-{C}adilhac, {F}. and {S}errato-{P}omar, {I}. {M}. and {R}achenne, {F}. and {C}howdhury, {A}. and {C}huo, {V}. and {A}zar, {S}. {R}. and {S}ingh, {M}. {K}. and {H}amel, {R}odolphe and {M}iss{\'e}, {D}oroth{\'e}e and {K}ini, {R}. {M}. and {K}enney, {L}. {J}. and {V}asilakis, {N}. and {M}arti-{R}enom, {M}. {A}. and {N}ir, {G}. and {P}ompon, {J}ulien and {G}arcia-{B}lanco, {M}. {A}.}, editor = {}, language = {{ENG}}, abstract = {{M}osquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. {T}here is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. {H}ere we report the discovery of high levels of the anti-immune subgenomic flaviviral {RNA} (sf{RNA}) in dengue virus 2-infected mosquito saliva. {W}e established that sf{RNA} is present in saliva using three different methods: northern blot, {RT}-q{PCR} and {RNA} sequencing. {W}e next show that salivary sf{RNA} is protected in detergent-sensitive compartments, likely extracellular vesicles. {I}n support of this hypothesis, we visualized viral {RNA}s in vesicles in mosquito saliva and noted a marked enrichment of signal from 3'{UTR} sequences, which is consistent with the presence of sf{RNA}. {F}urthermore, we show that incubation with mosquito saliva containing higher sf{RNA} levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. {T}ransfection of 3'{UTR} {RNA} prior to {DENV}2 infection inhibited type {I} and {III} interferon induction and signaling, and enhanced viral replication. {T}herefore, we posit that sf{RNA} present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission. {A}uthor summary{M}osquitoes transmit many viruses, such as those that cause dengue, introducing them in our bodies with the saliva that is deposited in our skins when they bite us. {S}cientists who study biting behavior and properties of mosquito saliva have concluded that there may be components in saliva that promote virus infection. {I}n this study we show that when dengue virus infects mosquitoes one can find in their saliva not only the expected dengue viruses but also a dengue virus product that can reduce our anti-virus defense systems. {I}t happens that this product is what is known as a non-coding {RNA}, a class of molecules that have recently been shown to mediate important biological regulation. {W}e propose that by introducing this {RNA} at the biting site dengue infected saliva prepares the terrain for an efficient infection and gives the virus an advantage in the first battle between it and our immune defenses.}, keywords = {}, booktitle = {}, journal = {{PL}o{S} {P}athogens}, volume = {19}, numero = {3}, pages = {e1011224 [29 ]}, ISSN = {1553-7366}, year = {2023}, DOI = {10.1371/journal.ppat.1011224}, URL = {https://www.documentation.ird.fr/hor/fdi:010087618}, }