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Zika, dengue viruses make victims smell better to mosquitoes

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The viruses that cause Zika and dengue fever can’t get from person to person on their own—they need to hitchhike inside a mosquito. A new study suggests how they hail these rides: They make their victims smell more attractive to the blood-sucking bugs.

It’s “a big advance,” says mosquito neuroscientist Laura Duvall of Columbia University, who wasn’t connected to the research. The work shows that “infection with these mosquito-borne viruses can alter the way some people smell … to make them more likely to be bitten.”

A person can give off a different body odor when ill, especially with an infection. COVID-19 patients, for instance, release a distinctive mixture of molecules that dogs and electronic “noses” can detect. Similarly, malaria parasites change the scent of human hosts, making them smell irresistible to mosquitoes.

Whether the viruses that cause Zika fever and dengue fever, which together infect up to 400 million people every year, also meddle with odor was unknown. These pathogens travel from person to person in Aedes aegypti mosquitoes, which also transmit the yellow fever and chikungunya viruses.

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To determine whether the insects are partial to individuals with Zika or dengue, microbiologist Gong Cheng of Tsinghua University and colleagues set up three interconnected cages for a mouse experiment. Into one cage they piped air that had blown across mice that were sick with the Zika virus. A second cage received air that had flowed over healthy mice. The team then added hungry mosquitoes to the third cage and let them choose where to hang out.

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Seventy percent of the mosquitoes crowded into the cage receiving air from the Zika-infected rodents, the scientists report online today in Cell. The insects’ distribution was equally lopsided when the air came from rodents with dengue fever rather than Zika. However, the mosquitoes didn’t favor a particular cage when the researchers sent the air from the infected animals’ cages through a filtration apparatus that trapped chemicals, suggesting the odor of the sick mice was drawing the insects.

People with dengue also produce this alluring scent, the team’s experiments suggested. The scientists wiped the armpits of healthy people and dengue fever patients with an absorbent material, isolated the molecules that could become airborne, and dabbed them onto filter paper. Mosquitoes preferred the bouquet of the dengue patients.

Hong Zhang, Yibin Zhu, and Gong Chen (left to right) demonstrate one of the test cages they used to investigate mosquito attraction to scents.Xuan Guo

By capturing and analyzing molecules emanating from infected rodents, the researchers identified the ingredients in eau de Zika or dengue. Mice gave off larger quantities of 11 potential odorants when they got sick, and further tests showed one of these molecules, acetophenone, was a mosquito attractant. Rodents that were ill exuded about 10 times more acetophenone than their uninfected counterparts. Patients with dengue also emitted more of the molecule than healthy people, the researchers discovered.

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Cheng and colleagues uncovered a way the viruses may jack up their host’s acetophenone release. Certain bacteria that dwell on the skin are the main source of acetophenone. Skin cells normally keep their numbers in check with a protein called RELMa that kills the microbes. However, the scientists found that mice infected with the Zika or dengue viruses cranked out much less RELMa, which might allow the bacteria to proliferate and change the animals’ scent.

The researchers tested that explanation by feeding mice isotretinoin, a derivative of vitamin A that increases RELMa synthesis, and then tallying how many mosquitoes bit the animals. The insects were less fond of mice that had consumed isotretinoin.

“It’s a very compelling paper,” says Ring Cardé of the University of California, Riverside, who studies chemical ecology and insect behavior. But he cautions that other research teams have uncovered numerous odor molecules that draw A. aegypti mosquitoes to their victims, including lactic acid and ammonia. “It’s not clear how this compound fits in with the known attractants.”

Still, the results could “revolutionize” diagnosis of the illnesses, says James Logan, a disease control specialist at the London School of Hygiene & Tropical Medicine who was part of the team that showed malaria parasites change people’s skin chemistry. Today, a blood test is necessary to determine whether a patient has Zika or dengue fever, and the results are not available immediately, he notes. An electronic nose that could detect acetophenone exuded by a person could provide a diagnosis much more quickly and without a blood sample, Logan says. A spinoff company he founded is developing sensors that could identify malaria from body odor, and similar technology might work for Zika and dengue, he says.

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In addition, the findings suggest “a novel avenue” to battle these diseases by reducing human attractiveness to mosquitoes, Cheng says. One strategy he and his colleagues are now testing involves giving isotretinoin or related compounds to dengue fever patients.

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