Flaviviruses make their hosts smell nicer to mosquitoes: study | Sci-News.com

New research shows that mosquito-borne flaviviruses such as Zika and dengue can manipulate the skin microbiota of their hosts to produce an odor that attracts mosquitoes.

dengue fever is spread by mosquitoes in tropical regions around the world, and occasionally in subtropical regions such as the southeastern US. It causes fever, rashes and aching pains, and sometimes bleeding and death. More than 50 million dengue cases occur every year.

Zika is another mosquito-borne viral disease in the family Flaviviridae† While it is uncommon for Zika to cause serious illness in adults, a recent outbreak in South America caused serious birth defects in the unborn children of infected pregnant women.

Yellow fever, Japanese encephalitis and West Nile also belong to this virus family.

These viruses require ongoing infections in both animal hosts and mosquitoes to spread. If one of these is missing – if all susceptible hosts remove the virus or all mosquitoes die – the virus disappears. For example, during the Philadelphia yellow fever outbreak in 1793, the arrival of the fall frost killed the local mosquitoes and ended the outbreak.

In tropical climates without the frost killing, there are always mosquitoes; the virus only needs one to bite an infected host animal to spread.

“Mosquitoes rely on their sense of smell to detect hosts and direct basic survival behaviors,” says Dr. Gong Cheng, a researcher at the Tsinghua University-Beijing University Joint Center for Life Sciences and the Institute of Infectious Diseases at the Shenzhen Bay Laboratory.

“At the beginning of this study, we found that the mosquitoes preferred to seek out and feed on dengue- and Zika-infected mice.”

To investigate why mosquitoes preferred infected hosts, Dr. Cheng and colleagues performed a chemical analysis on odor samples from infected mice and humans.

They identified the culprit that made them smell better as acetophenonethat was present at an abnormally high level in infected individuals.

This compound is also found in many fruits and some cheeses.

“We found that flaviviruses can use the increased release of acetophenone to help themselves reach their life cycles more effectively by making their hosts more attractive to mosquito vectors,” said Dr. cheng.

The researchers then examined exactly how dengue and Zika viruses increase acetophenone levels.

When a flavivirus invades a host, the virus engages in a fight with the cells in the host’s body to regulate the level of a key protein that controls the makeup of the skin microbiome – RELM†

When the cells win, RELMα keeps the acetophenone-producing bacteria in check.

“Intriguingly, both dengue and Zika viruses promoted the proliferation of acetophenone-producing skin bacteria by suppressing RELMα expression,” said Dr. cheng.

As a result, some bacteria multiply too much and produce more acetophenone.

With a better understanding of how flavivirus affects the skin microbiome, the authors set out to help the cells win the tug-of-war.

After examining existing RELMα literature, they decided to test whether isotretinoin — a vitamin A derivative commonly used as an acne medication — can suppress acetophenone production.

The experiment was simple: feed the mice isotretinoin and put them in a cage with mosquitoes.

The results were encouraging. The team found that mosquitoes did not feed on isotretinoin-treated infected mice any more than those who fed on uninfected animals.

“Dietary administration of isotretinoin, in flavivirus-infected animals, reduced acetophenone volatilization by reshaping the commensal bacteria present on the host skin,” said Dr. cheng.

The Results appear in the news Cell†

†

Hong Zhang et al† A volatile compound from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness. Cell, published online June 30, 2022; doi: 10.116/j.cell.2022.05.016