Dengue and Zika viruses alter the scent of their hosts to attract mosquitoes

Dengue and Zika viruses are transmitted through mosquito bites. Now, a study led by researchers in China shows that when humans and mice are infected with these viruses, they secrete a chemical that makes them more attractive to the mosquitoes that spread the viruses.

Almost half of the world's population lives in a dengue risk area. The lack of treatment means that many affected regions have high rates of morbidity and mortality. The new study, published in the magazine Cellhas found a way to reduce the release of this substance in mice and make mosquito bites less frequent: treatment with a commercial acne medication.

Both viruses, of the genus Flavivirus, depend on these insects to survive in nature. When a healthy mosquito bites an infected host, it can contract the infection, and then transmit it to other individuals through its bites.

The work shows that mosquitoes of the Aedes genus have host-seeking behavior, which may be driven by the scent of animals infected with these viruses. Aedes aegypti and Aedes albopictus species are vectors of Zika and dengue transmission.

Mosquitoes of the genus 'Aedes' have host-seeking behavior, which may be driven by the scent of infected animals.

"Mosquitoes rely on their sense of smell to detect their hosts," explains Gong Cheng, a researcher at Tsinghua University (Beijing) and lead author of the paper, "At the beginning of the study, we found that these vector insects preferred to search and feed of infected mice, compared to other healthy ones”.

A sophisticated strategy to increase infection

To investigate why mosquitoes preferred infected hosts, the team analyzed skin odor samples from both mice and infected humans to examine odor molecules in the epidermis. The researchers found that acetophenone, a substance that was present at an abnormally high level in the skin of infected individuals, is especially attractive to mosquitoes.

In humans and mice, acetophenone is produced by some bacteria of the Bacillus genus that grow on the skin. Normally, it produces an antimicrobial protein – called RELmalfa – that keeps bacilli populations at bay.

"Both the dengue virus and the Zika virus promote the proliferation of acetophenone-generating skin bacteria by suppressing the expression of RELMalfa," says Cheng. As a result, some bacteria replicate excessively and produce more acetophenone, making these diseased individuals more attractive to mosquitoes.

"Ultimately, the virus can manipulate the skin microbiome of its hosts to attract more mosquitoes and thus spread faster," says Penghua Wang, an immunologist at UConn Health (Connecticut, USA) academic medical center and co-author of the study.

Dengue-infected people were more attractive to mosquitoes and showed more acetophenone on their skin than healthy individuals

With the identity of the chemical compound revealed, the researchers found that when mice infected with dengue were given isotretinoin (an acne drug), they emitted less acetophenone, which reduced their attractiveness to mosquitoes.

This medicine is a derivative of vitamin A, known to increase the production of antimicrobial peptide in the skin.

The experiment was simple. The researchers fed the mice isotretinoin and put them in a cage with mosquitoes. They found that the mosquitoes did not feed on infected mice treated with the anti-acne drug any more than those that fed on uninfected animals.

As Cheng explains to SINC, "administration of isotretinoin through the diet in animals infected with flaviviruses reduces the production of acetophenone because it remodels the populations of bacteria on the host's skin."

Similar mechanisms in other viruses

"Although we don't have data for other flaviviruses, such as yellow fever or West Nile virus, we think there is a strong possibility that other of these viruses share similar mechanisms for manipulating their host's odor. For this reason, we will analyze other flaviviruses and alphaviruses transmitted by mosquitoes, under the same experimental conditions” continues Cheng.

In the future, the team plans to apply their findings in the real world. "We plan to administer isotretinoin in the diet of patients with dengue, in order to find out if this compound reduces the production of acetophenone in humans, as it occurs in mice," says the researcher.

The authors also plan a line of study in mosquitoes: "We want to identify specific olfactory receptors for acetophenone in these insects and eliminate genes from the mosquito population using gene drive technology," explains Cheng.

Without the receptors, mosquitoes will no longer be able to smell the skin molecule they love so much, possibly mitigating the spread of dengue and other flaviviruses, the authors conclude.

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