An international team of researchers has discovered an incredible way some viruses can alter the smell of their host in order to attract mosquitoes and spread to the next person. The study revealed Dengue and Zika viruses can alter a host’s skin microbiome to enhance the volume of odor molecules that draw in mosquitoes.
The new research arose from a simple observation. Odor is among a number of sensory cues that drive how mosquitoes select organisms to bite. And prior research has found mice infected with a malaria parasite generate distinct changes to their scent profiles. So, could viruses that rely on mosquitoes to spread, such as dengue or Zika, change the way their host smells in order to enhance their chances of transmission to the next person?
The first step in the research was simple – set a bunch of mosquitoes loose in chambers with infected and uninfected mice and see where they go. After several experiments the researchers did indeed observe greater volumes of mosquitoes moving towards mice infected with dengue or Zika.
About 20 different gaseous compounds were isolated from the infected mice. Testing each one individually the researchers discovered one chemical in particular attracted the most mosquitoes: acetophenone. Investigating the mice it was found those animals infected with dengue or Zika produced up to 10 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,” explained study co-author Penghua Wang, in a piece for The Conversation. “When we applied the dengue fever patient odors on one hand of a volunteer and a healthy person’s odor on the other hand, mosquitoes were consistently more attracted to the hand with dengue fever odors.”
The next step was to work out how the virus could be altering its host’s production of acetophenone. The researchers suspected the odor molecule was being emitted through the skin of the host organism, and this process was mediated by bacteria on the skin.
“When we compared the skin bacteria compositions of infected and uninfected mice, we identified that a common type of rod-shaped bacteria, Bacillus, was a major acetophenone producer and had significantly increased numbers on infected mice,” explained Wang. “This meant that the dengue and Zika viruses were able to change their host’s odor by altering the microbiome of the skin.”
Healthy skin produces an antimicrobial molecule called RELMα, and the researchers discovered infected mice had unusually low levels of this molecule. So it seems like the dengue and Zika viruses have developed a way to suppress a host’s RELMα levels, allowing for Bacillus bacteria to grow unchecked and produce greater volumes of acetophenone, which in turn attracts more mosquitoes and helps the virus to spread to a new host.
The final stage of the study looked at whether this mosquito-attracting viral mechanism could be prevented. Here the researchers turned to isotretinoin, a derivative of vitamin A previously found to enhance production of RELMα.
Treating infected mice with isotretinoin worked, reducing levels of Bacillus bacteria on the skin and increasing levels of RELMα. When infected mice were treated with isotretinoin, mosquitoes were no more attracted to them than uninfected mice.
Wang said the next step is to test this mechanism in human patients infected with dengue or Zika. If this is all validated in humans then it is possible transmission of these mosquito-borne viral diseases could be reduced by a simple isotretinoin treatment. It may even be possible to lower the broader impact of these viruses in the long-term by increasing dietary supplements of vitamin A in regions that struggle with these diseases.
The new study was published in the journal Cell.
New Atlas, 4 July 2022