Viruses such as dengue and the Zika virus are spread by mosquitoes, which ingest pathogens into human blood and pass them on to new victims. Researchers have now identified a mechanism that apparently helps viruses spread: they change the microbiome of our skin in such a way that they produce more substances that make us smell particularly attractive to mosquitoes. A drug that is already being used successfully against acne could possibly help. In mice infected with the dengue virus, the drug successfully stopped the changes in the skin microbiome that attracted mosquitoes and ensured that the animals were not bitten more often than healthy conspecifics. Human tests will follow.
To spread, so-called flaviviruses depend on human-to-human transmission by parasites. One of the best known representatives is the dengue virus, which is widespread in tropical areas of the world and which can cause fever, skin rashes and bleeding. More than 50 million people contract dengue fever each year, and around 20,000 die each year. Other members of the virus family are the Zika virus, which can cause birth defects, yellow fever, Japanese encephalitis, and West Nile virus.
Attractive for mosquitoes
A team led by Hong Zhang of Tsinghua University in Beijing has now discovered a trick used by viruses that apparently makes them more likely to spread: “We have observed that mosquitoes bite more and more mice infected with dengue or Zika virus,” the researchers explain. Based on this observation, they analyzed odor molecules on the skin of infected and healthy mice. And indeed: some odor molecules were more common in infected animals than in healthy ones. Zhang and his team tested the effects of these odorants by applying them to other mice and to the hands of human volunteers and observing how mosquitoes responded.
In this way, scientists have identified a molecule called acetophenone, which apparently provides a particularly attractive odor for mosquitoes. Using human dengue patients, they have shown that they also produce more acetophenone on the skin and thus attract mosquitoes. “Acetophenone is a volatile compound produced mainly by the skin microbiome,” explain the researchers. In healthy individuals, an antimicrobial protein called RELMα prevents the bacteria that produce acetophenone from overgrowing. “Flavivirus infection suppresses RELMα expression,” say the researchers. “This leads to the proliferation of acetophenone-producing bacteria and, consequently, to elevated levels of acetophenone.”
Acne medications as a remedy?
With this knowledge, the researchers set out to find a way to counteract this mosquito attraction mechanism. From other medical applications, a vitamin A derivative called isotretinoin has been known to increase the production of the antimicrobial RELMα in the skin. Until now, the remedy has been mainly used to treat severe acne. Zhang and his team gave this drug to mice infected with the dengue virus and put them in a cage with mosquitoes, along with untreated infected mice and healthy animals.
The result: Dengue mice fed the drug weren’t bitten any more often than their healthy counterparts. “Dietary administration of isotretinoin to flavivirus-infected animals reduced acetophenone shedding by remodeling resident bacteria on the host’s skin,” explains Zhang’s colleague Gong Cheng.
This could open up opportunities for infection prevention: if infected individuals are bitten fewer, this reduces the chances of spreading the virus and could help curb the spread of dengue fever. “In the future, we also want to test the dietary administration of isotretinoin preparations in patients with human dengue. In this way, we hope to reduce acetophenone-mediated activity of mosquitoes, “says Cheng. The researchers also want to address the problem from the mosquito side.” We plan to identify specific olfactory receptors for acetophenone in mosquitoes and remove genes from the mosquito population using gene drive technology, “explains Cheng. The genome of animals is modified with the help of genetic scissors and modified in such a way that all offspring inherit this genetic change. This accelerates the spread of the form. genetically modified in a population and could make mosquitoes insensitive to the odors of the attractants induced by the virus.
Those: Hong Zhang (Tsinghua-Universität, Beijing, China) et al., Cell, doi: 10.1016 / j.cell.2022.05.016