This article was originally published in The conversation.
Mosquitoes are the deadliest animal in the world. Hundreds of thousands of deaths each year are attributed to mosquito-borne diseases, including malaria, yellow fever, dengue fever, zika and chikungunya fever.
How mosquitoes seek out and feed on their hosts is an important factor in how a virus circulates in nature. Mosquitoes transmit diseases 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 who bites it.
For immunologists and infectious disease researchers like me, a better understanding of how a virus interacts with a host could offer new strategies for preventing and treating 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 human, to make it more attractive to mosquitoes, resulting in more bites that allow a virus to spread.
Mosquitoes locate a potential host through various sensory cues, such as B. Your body temperature and the carbon dioxide given off by your breath. Smells also play a role. Previous laboratory studies have found that mice infected with malaria have changes in their odor that make them more attractive to mosquitoes. With this in mind, my colleagues and I have wondered if other mosquito-borne viruses, such as dengue and zika, can also alter a person’s scent to make them more attractive to mosquitoes, and if there’s a way to prevent these changes.
To study 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 used airflow through the mouse chambers to direct 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 the reason why the mosquitoes were attracted to the infected mice because, although Zika-infected mice emitted less carbon dioxide than uninfected mice, dengue-infected mice did not change emission levels. Likewise, we excluded body temperature as a potential attraction factor when mosquitoes did not discriminate between mice with elevated or normal body temperature.
We then examined the role of body odors in increasing mosquito attraction 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 to infected and uninfected mice was comparable. This suggests that there was something about the odors from the infected mice that attracted the mosquitoes to them.
To identify the odor, we isolated 20 different gaseous chemical compounds from the odor of the infected mice. Of these, we found three that stimulated a significant response in mosquito antennae. When we applied these three compounds to the skin of healthy mice and the hands of human subjects, only one, acetophenone, attracted more mosquitoes compared to the control. We found that infected mice produced ten times more acetophenone than uninfected mice.
Similarly, we found that the odors collected from the armpits of dengue fever patients contained more acetophenone than those from healthy people. When we applied a dengue patient’s odor to one volunteer’s hand and a healthy person’s odor to the other hand, mosquitoes were consistently more attracted to the hand with dengue fever odor.
These results suggest that dengue and Zika viruses are able to increase the amount of acetophenone their hosts produce and excrete, 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 viruses increase the amount of mosquito-attracting acetophenone their hosts produce. In addition to being a chemical commonly used as a fragrance in perfumes, acetophenone is a metabolic byproduct commonly produced by certain bacteria that live on the skin and guts of humans 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 either the skin or gut bacteria from infected mice before exposing them to mosquitoes. Although mosquitoes were still more attracted to infected mice with depleted gut bacteria than uninfected mice, they were significantly less attracted to infected mice with depleted skin bacteria. These results suggest that skin microbes are a significant source of acetophenone.
When we compared the skin-bacterial compositions of infected and uninfected mice, we found that a common species of rod-shaped bacteria, bacillus, was a major acetophenone producer and had significantly increased numbers in infected mice. This meant that dengue and Zika viruses were able to alter their host’s scent by altering the skin’s microbiome.
Finally, we wondered if there was a way to prevent this odor change.
We found a possible option when we observed that infected mice had reduced levels of a key microbe-fighting molecule produced by skin cells called RELMα. This suggested that the dengue and Zika viruses suppressed production of this molecule, making the mice more susceptible to infection.
Vitamin A and its related chemical compounds are known to strongly boost RELMα production. So we fed a vitamin A derivative to infected mice for a few days and measured the amount of RELMα and bacillus Bacteria present on their skin and then exposed 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 and reduce the amount 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 humans and eventually apply what we have learned to patients. Vitamin A deficiency is widespread in developing countries. This is particularly the case in sub-Saharan Africa and Southeast Asia, where mosquito-borne viral diseases are widespread. 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 mosquito-borne diseases in the long term.