New research shows that mosquito-borne flaviviruses such as Zika and dengue can manipulate the microbiota of their hosts’ skin to produce an odor that attracts mosquitoes.
Zhang et al. observed that Aedes mosquitoes preferred to search for and feed on mice infected with dengue and Zika virus. Image credit: Zhang et al., Doi: 10.1016 / j.cell.2022.05.016.
Dengue is spread by mosquitoes in tropical areas around the world and occasionally in subtropical areas such as the southeastern United States. It causes fever, rash and painful aches and pains, and sometimes bleeding and death. More than 50 million cases of dengue occur each year.
Zika is another viral disease spread by mosquitoes in the Flaviviridae family. Although Zika is rare 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 are also members of this family of viruses.
These viruses require continuous infections in animal hosts and mosquitoes to spread. If any of these are missing, if all susceptible hosts eliminate the virus or all mosquitoes die, the virus disappears. For example, during the outbreak of yellow fever in Philadelphia in 1793, the arrival of the autumn frosts killed the local mosquitoes and the outbreak ended.
In tropical climates without killing frosts, there are always mosquitoes; the virus only needs one to bite an infected host animal to spread.
“Mosquitoes depend on their sense of smell to detect guests and guide key survival behaviors,” said Dr. Gong Cheng, a researcher at the Joint Center for Life Sciences at Tsinghua University and Beijing University and the Institute of Infectious Diseases of the Shenzhen Bay Laboratory. .
“At the beginning of this study, we found that mosquitoes preferred to look for and feed on mice infected with dengue and Zika.”
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 makes them smell more delicious like acetophenone, which was present at an abnormally high level in infected individuals.
This compound can also be found in many fruits and some cheeses.
“We have found that flaviviruses can use increased acetophenone release to help achieve their life cycles more effectively by making their hosts more attractive to mosquito vectors,” he said. Dr. Cheng.
The researchers then investigated exactly how dengue and Zika viruses increase the level of acetophenone.
When a flavivirus invades a host, the virus enters a tug-of-war with the host’s body cells to control the level of a key protein that regulates the composition of the skin’s microbiome: RELMα.
If cells are gaining, RELMα keeps acetophenone-producing bacteria under control.
“Interestingly, both dengue and Zika viruses promoted the proliferation of acetophenone-producing skin bacteria by suppressing RELMα expression,” Dr. Cheng said.
As a result, some bacteria multiply and produce more acetophenone.
With a clearer understanding of how flavivirus affects the skin microbiome, the authors set out to find a way to help cells gain the tug-of-war.
After examining the existing RELMα literature, they decided to test whether isotretinoin, a vitamin A derivative commonly used as a medicine for acne, can suppress acetophenone production.
The experiment was simple: feed the mice with 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 more than those that fed on uninfected animals.
“Dietary administration of isotretinoin, in flavivirus-infected animals, reduced the volatilization of acetophenone by remodeling the resident bacteria in the host’s skin,” Dr. Cheng said.
The results appear in the journal Cell.
_____
Hong Zhang et al. A volatile microbiota of the skin of flavivirus-infected hosts promotes the attractiveness of mosquitoes. Cell, published online June 30, 2022; doi: 10.1016 / j.cell.2022.05.016