05 July 2022

Infection to infection…

Viruses make us more attractive to mosquitoes

Anastasia Gorshkova, PCR.news

For the transmission of flaviviruses, which include Zika and dengue viruses, it is necessary that hematophagous mosquitoes detect an infected mammal, bite it and also transmit the virus to another mammal through the bite. Scientists from China and the United States have shown that flaviviruses can alter the host's skin microbiota, making the skin smell attractive to mosquitoes. They also identified a specific chemical that serves as an attractant for insects, and learned how to control its production with the help of a well-known acne medication.

It has previously been shown that people infected with malaria are more likely to be bitten by mosquitoes due to increased production of volatile attractants. The researchers decided to check whether infection with flaviviruses has a similar effect. They used a three-chamber system for experiments. Sixty female mosquitoes Aedes aegypti were released into the central chamber. From there, they could easily get into one of the traps located on both sides of the cell. Three mice knocked out by type I and type II interferon receptors were placed in each of the two side chambers (such mice are used to simulate infections with Zika and dengue viruses). In one side chamber there were healthy mice, in the other — infected with the Zika virus. The air from the chambers was fed into the traps.

On the 0th and 2nd days after infection, the same number of mosquitoes got into each of the traps. On days 4 and 6, the number of mosquitoes trapped next to infected mice was greater than that trapped next to uninfected mice (70% vs. 30%). Similar results were obtained in an experiment with mice infected with the dengue virus. When scientists put a smell filter between the animal chambers and mosquito traps, the whole effect disappeared. This means that the preference appears in mosquitoes only because of a special volatile attractant, and not because of body temperature or the behavior of rodents.

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To find out why mosquitoes prefer infected hosts, scientists analyzed the volatile substances that emit the bodies of infected mice and humans. The culprit of attracting mosquitoes was acetophenone. This compound is a product of the vital activity of many bacteria of the skin. It can also be found in some fruits and cheeses.

Next, the scientists sequenced the RNA of the skin cells of mice infected with viruses. It turned out that flaviviruses establish control over the level of RELMa, a key protein that regulates the composition of the skin microbiome. Normally, RELMa keeps the acetophenone-producing bacteria under control, but since viruses suppress protein expression, such bacteria begin to multiply intensively on the host body.

After analyzing the literature on RELMa, the scientists decided to check whether isotretinoin (13-cis-retinoic acid) — a derivative of vitamin A, which is used as a remedy for acne — can suppress the production of acetophenone. The experiment was simple: mice were injected with isotretinoin orally and repeated experiments with mosquitoes and traps. Ingestion of isotretinoin with food in animals infected with flaviviruses reduced the production of acetophenone due to changes in the composition of commensal bacteria on the host skin. As a result, the mosquitoes ceased to show great activity in relation to infected mice.

In the future, the researchers plan to administer isotretinoin to patients with dengue fever to reduce the likelihood of transmission of the virus with mosquitoes. This will not help cure already infected patients, but it will probably become an effective measure to control epidemics.

Currently, different ways of combating mosquito-borne infections are being considered. For example, the creation of mosquitoes resistant to viruses using genetic engineering.

Article by Zhang et al. A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attraction is published in the journal Cell.

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