@article{fdi:010086961, title = {{C}haracterization of dengue virus 3 ' {UTR} {RNA} binding proteins in mosquitoes reveals that {A}e{S}taufen reduces subgenomic flaviviral {RNA} in saliva}, author = {{Y}eh, {S}. {C}. and {D}iosa-{T}oro, {M}. and {T}an, {W}. {L}. and {R}achenne, {F}. and {H}ain, {A}. and {Y}eo, {C}. {P}. {X}. and {B}ribes, {I}. and {X}iang, {B}. {W}. {W}. and {K}annan, {G}. {S}. and {M}anuel, {M}. {C}. and {M}iss{\'e}, {D}oroth{\'e}e and {M}ok, {Y}. {K}. and {P}ompon, {J}ulien}, editor = {}, language = {{ENG}}, abstract = {{D}engue viruses ({DENV}) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly {A}edes aegypti. {A}s {RNA} viruses, {DENV} rely on {RNA}-binding proteins ({RBP}s) to complete their life cycle. {A}lternatively, {RBP}s can act as restriction factors that prevent {DENV} multiplication. {W}hile the importance of {RBP}s is well-supported in humans, there is a dearth of information about their influence on {DENV} transmission by mosquitoes. {S}uch knowledge could be harnessed to design novel, effective interventions against {DENV}. {H}ere, we successfully adapted {RNA}-affinity chromatography coupled with mass spectrometry-a technique initially developed in mammalian cells-to identify {RBP}s in {A}e. aegypti cells. {W}e identified fourteen {RBP}s interacting with {DENV} serotype 2 3'{UTR}, which is involved in the viral multiplication and produces subgenomic flaviviral {RNA} (sf{RNA}). {W}e validated the {RNA} affinity results for two {RBP}s by confirming that {A}e{P}ur binds the 3'{UTR}, whereas {A}e{S}taufen interacts with both 3'{UTR} and sf{RNA}. {U}sing in vivo functional evaluation, we determined that {RBP}s like {A}e{R}an, {A}e{E}xo{RN}ase, and {A}e{RN}ase have pro-viral functions, whereas {A}e{GTP}ase, {A}e{A}tu, and {A}e{P}ur have anti-viral functions in mosquitoes. {F}urthermore, we showed that human and mosquito {P}ur homologs have a shared affinity to {DENV}2 {RNA}, although the anti-viral effect is specific to the mosquito protein. {I}mportantly, we revealed that {A}e{S}taufen mediates a reduction of g{RNA} and sf{RNA} copies in several mosquito tissues, including the salivary glands and that {A}e{S}taufen-mediated sf{RNA} reduction diminishes the concentration of transmission-enhancing sf{RNA} in saliva, thereby revealing {A}e{S}taufen's role in {DENV} transmission. {B}y characterizing the first {RBP}s that associate with {DENV}2 3'{UTR} in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of {RBP}s in virus-vector interactions.}, keywords = {}, booktitle = {}, journal = {{PL}o{S} {P}athogens}, volume = {18}, numero = {9}, pages = {e1010427 [25 p.]}, ISSN = {1553-7366}, year = {2022}, DOI = {10.1371/journal.ppat.1010427}, URL = {https://www.documentation.ird.fr/hor/fdi:010086961}, }