title: Stability and loss of a virus resistance phenotype over time in transgenic mosquitoes harbouring an antiviral effector gene.
abstract: Transgenic Aedes aegypti were engineered to express a virus-derived, inverted repeat (IR) RNA in the mosquito midgut to trigger RNA interference (RNAi) and generate resistance to dengue virus type 2 (DENV2) in the vector. Here we characterize genotypic and phenotypic stabilities of one line, Carb77, between generations G(9) and G(17). The anti-DENV2 transgene was integrated at a single site within a noncoding region of the mosquito genome. The virus resistance phenotype was strong until G(13) and suppressed replication of different DENV2 genotypes. From G(14)-G(17) the resistance phenotype to DENV2 became weaker and eventually was lost. Although the sequence of the transgene was not mutated, expression of the IR effector RNA was not detected and the Carb77 G(17) mosquitoes lost their ability to silence the DENV2 genome.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA. afranz@colostate.edu
authors.forename: A W E
authors.initials: AW
authors.lastname: Franz
authors.forename: I
authors.initials: I
authors.lastname: Sanchez-Vargas
authors.forename: J
authors.initials: J
authors.lastname: Piper
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.forename: C C H
authors.initials: CC
authors.lastname: Khoo
authors.forename: A A
authors.initials: AA
authors.lastname: James
authors.forename: K E
authors.initials: KE
authors.lastname: Olson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000998:Antiviral Agents / Q000378:metabolism*; D001483:Base Sequence; D009033:Culicidae / Q000235:genetics* / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D005260:Female; D017344:Genes, Insect; D005838:Genotype; D040582:Inheritance Patterns / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D010641:Phenotype; D013997:Time Factors
chemical_list: D000998:Antiviral Agents