Exome-wide association study reveals largely distinct gene sets underlying specific resistance to dengue virus types 1 and 3 in Aedes aegypti


Autoři: Laura B. Dickson aff001;  Sarah H. Merkling aff001;  Mathieu Gautier aff002;  Amine Ghozlane aff003;  Davy Jiolle aff001;  Christophe Paupy aff004;  Diego Ayala aff004;  Isabelle Moltini-Conclois aff001;  Albin Fontaine aff001;  Louis Lambrechts aff001
Působiště autorů: Insect-Virus Interactions Unit, Institut Pasteur, UMR2000, CNRS, Paris, France aff001;  CBGP, INRAE, CIRAD, IRD, Montpellier SupAgro, Univ. Montpellier, Montpellier, France aff002;  Hub de Bioinformatique et Biostatistique–Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS, Paris, France aff003;  MIVEGEC, Univ. Montpellier, IRD, CNRS, Montpellier, France aff004;  Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville, Gabon aff005
Vyšlo v časopise: Exome-wide association study reveals largely distinct gene sets underlying specific resistance to dengue virus types 1 and 3 in Aedes aegypti. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008794
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008794

Souhrn

Although 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. In the mosquito Aedes 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. In particular, it is unknown whether DENV type- or strain-specific resistance relies on allelic variants of the same genes or on distinct gene sets. Here, we investigated the genetic architecture of DENV resistance in a population of Ae. aegypti from Bakoumba, Gabon, which displays a stronger resistance phenotype to DENV type 1 (DENV-1) than to DENV type 3 (DENV-3) infection. Following 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. Using 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. Among 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. The 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. Together, these results indicate that specific resistance to different DENV types relies on largely non-overlapping sets of genes in this Ae. aegypti population and pave the way for further mechanistic studies.

Klíčová slova:

Aedes aegypti – Dengue virus – Gabon – Gene pool – Host-pathogen interactions – Mosquitoes – Population genetics – Invertebrate genetics


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