orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET
Open accessAbstract
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.
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DEET is primarily regarded as a behavioral repellent acting largely through olfactory pathways rather than by eliciting VGSC-mediated neurotoxicity typical of pyrethroids.
“In comparison, DEET is primarily regarded as a behavioral repellent acting largely through olfactory pathways—by modulating odorant receptor signaling and/or reducing the effective delivery of host odors to olfactory receptor neurons—rather than by eliciting VGSC-mediated neurotoxicity typical of pyrethroids (DeGennaro et al., 2013).”
From Do natural or synthetic excito-repellents work better? A study on coastal malaria vector <i>Anopheles epiroticus</i> in Ko Chang, Thailand (2026) · cites this paper as DeGennaro et al., 2013
The paper’s Abstract reports that volatile DEET repels control mosquitoes but not orco mutants, supporting an olfactory pathway for its repellent effect. It discusses odorant-receptor modulation as a possible mechanism, but does not establish reduced delivery of host odors to olfactory neurons or address VGSC-mediated neurotoxicity and pyrethroids. It also reports a distinct contact-mediated repellent effect. (LLM, conf=0.86)
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Self-citation
- Authors
- DeGennaro, M., McBride, C. S., Seeholzer, L., Nakagawa, T., Dennis, E. J., Goldman, C., Jasinskiene, N., James, A. A., & Vosshall, L. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Rockefeller University (US)
- University of California, Irvine (US)
- Corresponding author
- Vosshall, Leslie B.
- ORCID
- Venue
- Nature
- Published
- 2013-05-29
- Volume
- 498
- Issue
- 7455
- Pages
- 487-491
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3696029
- OpenAlex
- W2021253771
- Cited by
- 473
- References
- 39
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 36 · 2023: 39 · 2022: 62 · 2021: 47 · 2020: 45 · 2019: 41 · 2018: 30 · 2017: 21 · 2016: 31 · 2015: 26 · 2014: 27 · 2013: 14
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institute on Deafness and Other Communication Disorders (DC012069, K99DC012069, R00DC012069)
- National Institute of Allergy and Infectious Diseases (R37AI029746, R01AI029746, AI29746)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Agricultural and Biological Sciences › Insect Science › Insect Pheromone Research and Control
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Insect Pest Control Strategies
- Keywords
- Orco, mosquito host preference, Aedes aegypti, Anopheles gambiae, olfactory receptors, olfactory sensory neurons, mosquito olfaction, host-seeking behavior, gene targeting, zinc finger nucleases
- MeSH terms
- Aedes, Amino Acid Sequence, Animals, Base Sequence, DEET, Drug Resistance, Female, Honey, Humans, Insect Repellents, Male, Molecular Sequence Data, Mutation, Neurons, Odorants, Olfactory Pathways, Volatilization, Mutagenesis, Site-Directed, Genes, Insect, Host Specificity
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