Mosquitoes can be choosy about who they hang out with, swarming around some people while totally avoiding others.
And it turns out some viral infections can make you especially attractive to the tiny blood suckers.
A new study has found that getting infected with a virus like dengue or Zika can make you smell delicious to mosquitoes, the flying carriers of these infections.
Once infected, mice and humans secrete a compound that's like catnip to mozzies, leading them to bite their hosts, suck their blood and carry the virus to their next victim, according to the research published today in the journal Cell.
"Mosquitoes need to actively seek and feed on [an infected] host to acquire infectious viral particles," said lead author Gong Cheng, an immunologist at Tsinghua University in Beijing.
"The viruses subsequently establish an infection in the mosquitoes, thereby enabling them to transmit viruses to naive hosts through blood feeding."
Deadly disease vectors
It's no secret that mosquitoes are a bit of a nuisance, but they can also be dangerous disease carriers, particularly in tropical regions.
Among the infections mosquitoes spread are flaviviruses — a family that includes dengue, Zika, Japanese encephalitis, and yellow fever.
Dengue alone affects over 50 million people each year, leading to roughly 20,000 deaths.
These viruses need to be continually taken up by mosquitoes and human hosts in order to spread and survive, Professor Cheng said.
Mosquitoes rely on their sense of smell to find their next meal, and previous studies have found that malaria infections — another mosquito-borne disease caused by a parasite — can change people's scent, making them more attractive to mozzies.
Professor Cheng and his team wondered whether dengue and Zika infections also produced a mosquito-drawing odour.
To the find out, the researchers placed 60 Aedes aegypti mosquitoes into a special enclosure.
Three Zika-infected mice were placed inside a chamber at one end of the enclosure, while three healthy mice were placed inside another chamber on the opposite side.
After six days, the researchers counted how many mozzies ended up in each chamber.
They found that about 70 per cent had buzzed their way into the infected mouse chamber.
When the team tried out the same experiment with dengue-infected mice, the mosquitoes were also more attracted to them than their healthy counterparts, indicating there was something appealing about the virus-laden mice.
A chemical cocktail
Next, the team wanted to find out what chemicals were making the sick mice so mouth watering to the mosquitoes.
They placed the healthy and infected mice into separate glass chambers that were each connected to a filter.
After blasting the mice with air for eight hours to get a whiff of their odour, Dr Cheng and his team analysed the compounds each filter had collected.
They found abnormally high levels of 20 compounds among the Zika and dengue-infected mice.
The team then exposed the mosquitoes to each compound and measured the electrical activity in their antennae to see which one they responded to the most.
Three of these compounds — acetophenone, decanal and styrene — triggered the strongest responses in the mosquitoes' antennae.
Taking things a step further, the researchers dabbed a bit of each chemical onto the mice to see which one was the top mosquito magnet.
Of all the compounds, the mosquitoes went wildest for acetophenone, a compound naturally found in apples, cheese and beef.
But the team wanted to see whether the presence of this delicious-smelling chemical was also present in humans with dengue fever.
So, they took swabs from the armpits of 16 dengue patients and 16 healthy people and rubbed them onto pieces of filter paper.
They then invited volunteers into the lab and placed a piece of this smelly paper on one hand.
For comparison, the team placed a blank piece of filter paper on their other hand.
The volunteers then stuck their hands into the mosquito box for 30 minutes.
Again, the mosquitoes made a beeline for the hands covered in armpit odour from the dengue patients.
"The dengue patient odour attracted more mosquitoes than the control," said study co-author Penghua Wang, an immunologist at the University of Connecticut Health Center.
Like the mice, chemical analyses of the armpit extracts showed that acetophenone was unusually high in the skin of human dengue patients.
Smell-producing microbes
But where was this tasty-smelling chemical coming from?
The researchers suspected that the acetophenone was being produced by bacteria living on the skin of the infected mice.
When the researchers profiled the skin microbiota of healthy and infected mice, they found that sick mice were crawling with rod-shaped Bacillus bacteria, the biggest producers of acetophenone, Dr Wang said.
Genetic analyses reveals that when dengue or Zika viruses invade their host, they suppress the expression of an antimicrobial protein called RELMα, which usually keeps the skin microbiome in balance.
When this protein is blocked by a viral infection, Bacillus bacteria spread like wildfire on the skin and produce more mosquito-attracting acetophenone.
This creates a vicious infection cycle, Professor Cheng said.
"This phenomenon facilitates mosquitoes to actively seek, locate and feed on the [infected] hosts to acquire the virus," he said.
Can acne medication break the cycle?
Once the team had figured out what was making dengue and Zika-infected mice so tasty to mosquitoes, they wanted to see if there was a way to reduce the amount of acetophenone they were giving off.
They turned to isotretinoin — a vitamin A derivative that's commonly used in acne medications.
It worked wonders. When the researchers fed isotretinoin to the infected mice, they found the mosquitoes didn't bite the sick mice any more than the healthy ones.
The Bacillus bacteria on the skin of the infected mice was also greatly reduced, which in turn led to less acetophenone in their body odour.
Leon Hugo, a medical entomologist at the QIMR Berghofer Medical Research Institute, welcomed the findings.
He said they revealed important new insights into how mosquito-borne viruses interact with their hosts, and the underlying factors that attract mosquitoes.
"The study reveals a complex and intriguing mechanism," said Dr Hugo, who was not involved in the study.
Dr Hugo said the research could also be used to develop strategies to stop mosquitoes from seeking out and biting infected hosts, though clinical trials in humans would be needed to see if isotretinoin worked in the real world.
The next steps for Professor Cheng and his team are to pinpoint the receptors that allow mosquitoes to sniff out acetophenone, and knock out the genes associated with them.
If mosquitoes can't smell the acetophenone they crave, they are less likely to bite infected patients and spread the virus further.
The researchers are also planning on trialling isotretinoin in dengue patients in Malaysia later this year to see if it could help break the infection cycle.
"We hope to provide a strategy for disease control," Professor Cheng said.
