This article was originally published on The Conversation.
Mosquitoes are the deadliest animal in the world. Hundreds of thousands of deaths a year are attributed to mosquito-borne diseases such as malaria, yellow fever, dengue, Zika, and chikungunya.
The way mosquitoes seek out and feed on their hosts are important factors in how a virus circulates in nature. Mosquitoes spread disease by acting as carriers of viruses and other pathogens: a mosquito that bites a person infected with a virus can pick up the virus and pass it on to the next person it bites.
For immunologists and infectious disease researchers like myself, a better understanding of how a virus interacts with a host may offer new strategies to prevent and treat mosquito-borne diseases. In our recently published study, my colleagues and I found that some viruses can alter the body odor of a mouse, and perhaps a person, to make them more attractive to mosquitoes, leading to more bites that allow the virus to spread. propagate
Mosquitoes locate a potential host through different sensory signals, such as their body temperature and the carbon dioxide emitted from their breath. Odors also play a role. Previous laboratory research has found that malaria-infected mice have changes in their odors that make them more attractive to mosquitoes. With this in mind, my colleagues and I wondered if other mosquito-borne viruses, such as dengue and Zika, can also change a person’s odor to make them more attractive to mosquitoes, and if there is any way to prevent these changes. .
To investigate this, we placed mice infected with dengue or Zika virus, uninfected mice, and mosquitoes in one of three arms of a glass chamber. When we applied airflow through the chambers of the mice to channel their odors to the mosquitoes, we found that more mosquitoes chose to fly to the infected mice than to the uninfected mice.
We ruled out carbon dioxide as a reason why mosquitoes were attracted to infected mice, because although Zika-infected mice emitted less carbon dioxide than uninfected mice, dengue-infected mice did not change emission levels. . Likewise, we ruled out body temperature as a potential attractive factor when the mosquitoes did not differentiate between mice with elevated or normal body temperature.
We then evaluated the role of body odors in the increased attraction of mosquitoes to infected mice. After placing a filter in the glass chambers to prevent mouse odors from reaching the mosquitoes, we found that the number of mosquitoes flying towards infected and uninfected mice was comparable. This suggests that there was something about the odors of the infected mice that drew the mosquitoes to them.
To identify the odour, we isolated 20 different gaseous chemical compounds from the odor emitted by infected mice. Of these, we found three to stimulate a significant response in mosquito antennae. When we applied these three compounds to the skin of healthy mice and to the hands of human volunteers, only one, acetophenone, attracted more mosquitoes compared to the control. We found that the infected mice produced 10 times more acetophenone than the uninfected mice.
Similarly, we found that odors collected from the armpits of dengue patients contained more acetophenone than those of healthy people. When we applied the odors of a dengue patient to one hand of a volunteer and the odor of a healthy person to the other hand, mosquitoes were more attracted to the dengue-scented hand.
These findings imply that dengue and Zika viruses are capable of increasing the amount of acetophenone their hosts produce and emit, making them even more attractive to mosquitoes. When uninfected mosquitoes bite these attractive hosts, they can bite other people and spread the virus even further.
Next, we wanted to find out how the viruses increased the amount of mosquito-attracting acetophenone produced by their hosts. Acetophenone, in addition to being a chemical commonly used as a fragrance in perfumes, is also a metabolic byproduct commonly produced by certain bacteria that live on the skin and in the intestines of people and mice. So we wondered if it had something to do with changes in the type of bacteria on the skin.
To test this idea, we removed the skin or gut bacteria of infected mice before exposing them to mosquitoes. Although mosquitoes were still more attracted to mice infected with depleted gut bacteria compared to uninfected mice, they were significantly less attracted to mice infected with depleted skin bacteria. These results suggest that skin microbes are an essential source of acetophenone.
When we compared the compositions of bacteria from the skin of infected and uninfected mice, we identified that a common type of rod-shaped bacteria, Bacillus, was a major producer of acetophenone and had significantly higher numbers in infected mice. This meant that dengue and Zika viruses were able to change their host’s odor by altering the skin microbiome.
Finally, we wondered if there was any way to prevent this change in odors.
We found a potential option when we observed that the infected mice had reduced levels of an important microbe-fighting molecule produced by skin cells, called RELMα. This suggested that dengue and Zika viruses suppressed the production of this molecule, making the mice more vulnerable to infection.
Vitamin A and its related chemical compounds are known to strongly increase RELMα production. So we fed infected mice a vitamin A derivative over the course of a few days and measured the amount of RELMα and Bacillus bacteria present on their skin, and then exposed them to mosquitoes.
We found that infected mice treated with the vitamin A derivative were able to restore their RELMα levels to those of uninfected mice, as well as reduce the number of Bacillus bacteria on their skin. Mosquitoes were also no more attracted to these treated infected mice than to uninfected mice.
Our next step is to replicate these results in people and eventually apply what we learn to patients. Vitamin A deficiency is common in developing countries. This is especially the case in sub-Saharan Africa and Southeast Asia, where mosquito-borne viral diseases are prevalent. We will investigate whether dietary vitamin A or its derivatives could reduce the attraction of mosquitoes to people infected with Zika and dengue and subsequently reduce mosquito-borne diseases in the long term.