@article{fdi:010070861,
  title = {{D}engue subgenomic flaviviral {RNA} disrupts immunity in mosquito salivary glands to increase virus transmission},
  author = {{P}ompon, {J}ulien and {M}anuel, {M}. and {N}g, {G}. {K}. and {W}ong, {B}. and {S}han, {C}. and {M}anokaran, {G}. and {S}oto-{A}costa, {R}. and {B}radrick, {S}. {S}. and {O}oi, {E}. {E}. and {M}iss{\'e}, {D}oroth{\'e}e and {S}hi, {P}. {Y}. and {G}arcia-{B}lanco, {M}. {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{G}lobally re-emerging dengue viruses are transmitted from human-to-human by {A}edes mosquitoes. {W}hile viral determinants of human pathogenicity have been defined, there is a lack of knowledge of how dengue viruses influence mosquito transmission. {I}dentification of viral determinants of transmission can help identify isolates with high epidemiological potential. {A}dditionally, mechanistic understanding of transmission will lead to better understanding of how dengue viruses harness evolution to cycle between the two hosts. {H}ere, we identified viral determinants of transmission and characterized mechanisms that enhance production of infectious saliva by inhibiting immunity specifically in salivary glands. {C}ombining oral infection of {A}edes aegypti mosquitoes and reverse genetics, we identified two 3'{UTR} substitutions in epidemic isolates that increased subgenomic flaviviral {RNA} (sf{RNA}) quantity, infectious particles in salivary glands and infection rate of saliva, which represents a measure of transmission. {W}e also demonstrated that various 3'{UTR} modifications similarly affect sf{RNA} quantity in both whole mosquitoes and human cells, suggesting a shared determinism of sf{RNA} quantity. {F}urthermore, higher relative quantity of sf{RNA} in salivary glands compared to midgut and carcass pointed to sf{RNA} function in salivary glands. {W}e showed that the {T}oll innate immune response was preferentially inhibited in salivary glands by viruses with the 3'{UTR} substitutions associated to high epidemiological fitness and high sf{RNA} quantity, pointing to a mechanism for higher saliva infection rate. {B}y determining that sf{RNA} is an immune suppressor in a tissue relevant to mosquito transmission, we propose that 3'{UTR}/sf{RNA} sequence evolution shapes dengue epidemiology not only by influencing human pathogenicity but also by increasing mosquito transmission, thereby revealing a viral determinant of epidemiological fitness that is shared between the two hosts.},
  keywords = {},
  booktitle = {},
  journal = {{PLOS} {P}athogens},
  volume = {13},
  numero = {7},
  pages = {e1006535 [27 p.]},
  ISSN = {1553-7366},
  year = {2017},
  DOI = {10.1371/journal.ppat.1006535},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070861},
}