title: orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET.
abstract: Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.
authors.affiliation: Laboratory of Neurogenetics and Behavior, and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: DeGennaro
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: McBride
authors.forename: Laura
authors.initials: L
authors.lastname: Seeholzer
authors.forename: Takao
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Dennis
authors.forename: Chloe
authors.initials: C
authors.lastname: Goldman
authors.forename: Nijole
authors.initials: N
authors.lastname: Jasinskiene
authors.forename: Anthony A
authors.initials: AA
authors.lastname: James
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Vosshall
mesh_terms: D000330:Aedes / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003671:DEET / Q000008:administration & dosage / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D017344:Genes, Insect / Q000235:genetics*; D006722:Honey; D058507:Host Specificity / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007302:Insect Repellents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009812:Odorants / Q000032:analysis; D009833:Olfactory Pathways / Q000166:cytology / Q000187:drug effects; D014835:Volatilization
chemical_list: D007302:Insect Repellents; D003671:DEET