This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.
As the nights get warmer here in Connecticut, I'm spending more and more time at dusk outside with my family. And alongside the ritual of roasting marshmallows for s'mores comes another ritual: complaining about who is getting bitten more by mosquitoes.
Why is it that I am relatively spared from those pesky vectors of disease while my wife and son are positively swarmed? I always joke that it's because they are sweeter.
And it turns out that I may not be far off the mark. A new paper in the journal Cell has shown not only that mosquitoes are attracted to certain smells, but also that certain mosquito-borne viruses change how we smell. The infection calls the mosquitoes in.
It's a crazy bit of evolution and a potential new avenue to decrease the spread of vector-borne diseases.
The idea that vector-borne diseases make you more attractive to the given vector is not entirely new. In fact, this phenomenon has been pretty clearly demonstrated in malaria. Controlled experiments have found that individuals infected with the malaria parasite are bitten more than control individuals.
But mosquitoes harbor more diseases than malaria. Flaviviruses like dengue and Zika virus — the latter becoming steadily more prevalent in the United States — lead to tens of millions of infections a year. And until now, no one has shown whether they can change our attractiveness to mosquitoes like malaria does.
But now researchers led by Gong Cheng in China have demonstrated, fairly conclusively, that these viruses do more than infect astrocytes, trophoblasts, and monocytes. They make us more appealing to mosquitoes, too. Cheng and colleagues also show us almost exactly how it works. The experimental setup is pretty clever.
It looks like this. Put a bunch of mosquitoes in a chamber. On one side, you put a mouse infected with a flavivirus like Zika. On the other, an uninfected mouse.
The researchers showed that, instead of the 50/50 mosquito split you would ordinarily see, 70% of mosquitoes head toward the Zika-infected mouse.
Of course, infection does a lot of things, including causing fevers. To prove that the mosquitoes weren't just being attracted to higher body temperatures, the researchers injected mice with lipopolysaccharide, a potent fever inducer. The mosquitoes didn't seem to care. They were equally attracted to control mice and febrile mice, provided that the latter were not actually infected with a flavivirus.
Mosquitoes like carbon dioxide, we're told, but it turns out that as the mice get sick from Zika infection, they actually generate less carbon dioxide than uninfected mice — so that's not what's driving the blood-suckers.
Could it be that infected mice smell different?
To test this, the researchers put a smell filter between the mice and the mosquitoes, something that would block all those odorant molecules. Now the mosquitoes had no particular preference between infected and uninfected mice.
It was becoming clear that smell was the thing, so the researchers did what any self-respecting scientist with access to a mass spectrometer would do: they identified every volatile compound coming from infected and uninfected mice, ultimately identifying 11 compounds that were fairly dramatically upregulated in infection.
Which of those drive the mosquitoes crazy? Well, they systematically exposed mosquitoes to each of the 11 chemicals to see which ones made their antennas twitch most.
(I'm told that this is a good signal that the smell is attractive to the mosquito.) One stood out above the rest: acetophenone. It was about 10 times higher in infected mice compared with uninfected mice. And sure enough, if you paint some acetophenone on healthy mice, or human hands, the mosquitoes love it.
Acetophenone is an aromatic ketone which apparently smells something like almond. Perfumers use it for its notes of cherry and honeysuckle as well, though you probably wouldn't want to wear those particular perfumes in dengue country.
Through some clever analysis of skin bacteria, the researchers were even able to determine how exactly flaviviruses promote this smell. Basically, they inhibit an antibacterial molecule called resistin-like molecule alpha. Without that substance on the skin, the bacteria flora starts to change, leading to the growth of bacteria that produce — you guessed it — acetophenone.
Now, of course, this is a mouse study primarily, but the researchers actually recruited patients infected with dengue to confirm some of the findings. They showed, for example, that acetophenone levels were significantly higher in humans infected with dengue than controls. They also showed that mosquitoes were more attracted to the odor of dengue-infected humans. This was an experiment that involved swabbing the armpits of dengue-infected and healthy humans. The things we do for science.
Overall, this paper is a really impressive piece of work, highlighting the complex interplay of virus and primary and secondary hosts. It is a dramatic example of the power of evolution as well. Flaviviruses like Zika and dengue have no idea what a mosquito is, or that they require them for reproduction. But flaviviruses that make their hosts smell good to mosquitoes will have a competitive advantage. Flaviviruses, by exploiting a chain of infection from human, to mosquito, to human, to mosquito end up bringing humans and mosquitoes closer together. Breaking that chain is key to controlling these epidemics.
Now, I wanted to talk about this study mostly because it is really cool — just a nice piece of science. The truth is, we already have a lot of tools to fight vector-borne illnesses, ranging from the simple mosquito net to genetically engineered death mosquitoes that can reproduce but their offspring don't survive. Understanding how our smell changes how attractive mosquitoes find us doesn't mean we'll be avoiding bug spray anytime soon. But that's the thing about greater understanding. In retrospect, it can be easy to see where breakthroughs happen. In the moment, though, it is often unclear what new knowledge will lead to the world being changed. The best we can do is say, "Huh! This is pretty cool" and let the next group of scientists take the next step. But any step that brings us closer to an end of our age-old battle with mosquitoes will be a welcome one.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.
All images from Cell
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Cite this: F. Perry Wilson. Mosquitoes Go Viral if They Smell This on You - Medscape - Jun 30, 2022.