@article{fdi:010078166,
  title = {{E}xome-wide association study reveals largely distinct gene sets underlying specific resistance to dengue virus types 1 and 3 in {A}edes aegypti},
  author = {{D}ickson, {L}. {B}. and {M}erkling, {S}. {H}. and {G}autier, {M}. and {G}hozlane, {A}. and {J}iolle, {D}. and {P}aupy, {C}hristophe and {A}yala, {D}iego and {M}oltini-{C}onclois, {I}. and {F}ontaine, {A}. and {L}ambrechts, {L}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}lthough specific interactions between host and pathogen genotypes have been well documented in invertebrates, the identification of host genes involved in discriminating pathogen genotypes remains a challenge. {I}n the mosquito {A}edes aegypti, the main dengue virus ({DENV}) vector worldwide, statistical associations between host genetic markers and {DENV} types or strains were previously detected, but the host genes underlying this genetic specificity have not been identified. {I}n particular, it is unknown whether {DENV} type- or strain-specific resistance relies on allelic variants of the same genes or on distinct gene sets. {H}ere, we investigated the genetic architecture of {DENV} resistance in a population of {A}e. aegypti from {B}akoumba, {G}abon, which displays a stronger resistance phenotype to {DENV} type 1 ({DENV}-1) than to {DENV} type 3 ({DENV}-3) infection. {F}ollowing experimental exposure to either {DENV}-1 or {DENV}-3, we sequenced the exomes of large phenotypic pools of mosquitoes that are either resistant or susceptible to each {DENV} type. {U}sing variation in single-nucleotide polymorphism ({SNP}) frequencies among the pools, we computed empirical p values based on average gene scores adjusted for the differences in {SNP} counts, to identify genes associated with infection in a {DENV} type-specific manner. {A}mong the top 5% most significant genes, 263 genes were significantly associated with resistance to both {DENV}-1 and {DENV}-3, 287 genes were only associated with {DENV}-1 resistance and 290 were only associated with {DENV}-3 resistance. {T}he shared significant genes were enriched in genes with {ATP} binding activity and sulfur compound transmembrane transporter activity, whereas the genes uniquely associated with {DENV}-3 resistance were enriched in genes with zinc ion binding activity. {T}ogether, these results indicate that specific resistance to different {DENV} types relies on largely non-overlapping sets of genes in this {A}e. aegypti population and pave the way for further mechanistic studies. {A}uthor summary {C}ompatibility between hosts and pathogens is often genetically specific in invertebrates but host genes underlying this genetic specificity have not been elucidated. {W}e investigated the genetic architecture of dengue virus type-specific resistance in the mosquito vector {A}edes aegypti. {W}e used a natural population of {A}e. aegypti from {B}akoumba, {G}abon, which is differentially resistant to dengue virus type 1 and dengue virus type 3. {W}e surveyed genetic variation in protein-coding regions of the mosquito genome and compared the frequency of genetic polymorphisms between groups of mosquitoes that are either resistant or susceptible to each dengue virus type. {W}e found that the {A}e. aegypti genes associated with resistance to dengue virus type 1 or dengue virus type 3 were largely non-overlapping. {T}his finding indicates that different sets of host genes, rather than different variants of the same genes, confer pathogen-specific resistance in this population. {T}his study is an important step towards identification of mechanisms underlying the genetic specificity of invertebrate host-pathogen interactions.},
  keywords = {},
  booktitle = {},
  journal = {{PL}o{S} {G}enetics},
  volume = {16},
  numero = {5},
  pages = {art. e1008794 [19 ]},
  ISSN = {1553-7404},
  year = {2020},
  DOI = {10.1371/journal.pgen.1008794},
  URL = {https://www.documentation.ird.fr/hor/fdi:010078166},
}