Cell
Volume 185, Issue 14, 7 July 2022, Pages 2510-2522.e16
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Article
A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness

https://doi.org/10.1016/j.cell.2022.05.016Get rights and content
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Highlights

  • Acetophenone from flavivirus-infected mice is a potent attractant for mosquitoes

  • Flavivirus infection promotes the expansion of acetophenone-producing skin bacteria

  • Flavivirus promotes the skin bacterial proliferation by suppressing RELMα

  • Administration of isotretinoin reduces the acetophenone cue and viral transmission

Summary

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

Keywords

flavivirus
mosquito
attraction
skin microbiota

Data and code availability

Raw RNA-seq data and 16S rDNA gene sequences for all samples used in this study have been deposited in the Short Read Archive and GEO (NCBI) and are publicly available as of the date of publication. These accession numbers for these datasets are listed in the key resources table. Original SDS-PAGE and western blot images have been deposited to Mendeley and are publicly available as of the date of publication. The DOI is listed in the key resources table. All other data that support the study are available from the lead contact upon reasonable request.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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8

These authors contributed equally

9

Lead contact