The viruses that cause Zika and dengue cannot pass from person to person on their own – they have to hitch a ride inside a mosquito. A new study suggests how they greet these rides: they make their victims smell more attractive to bloodsucking insects.
It’s “a major breakthrough,” says mosquito neuroscientist Laura Duvall of Columbia University, who was not linked to the research. The work shows that “infection with these mosquito-borne viruses can alter the smell of some people … to make them more prone to being bitten.”
A person may give off a different body odor when they are sick, especially with an infection. COVID-19 patients, for example, release a distinct mixture of molecules that dogs and electronic “noses” can detect. Likewise, malaria parasites alter the scent of human hosts, making them irresistible to mosquitoes.
Whether the viruses that cause Zika fever and dengue fever, which together infect up to 400 million people every year, also intrude with the odor was unknown. These pathogens travel from person to person in Aedes aegypti mosquitoes, which also transmit yellow fever and chikungunya viruses.
To determine whether the insects are biased towards individuals with Zika or dengue, microbiologist Gong Cheng of Tsinghua University and colleagues set up three interconnected cages for a mouse experiment. In a cage, they channeled the air they had blown into mice sick with the Zika virus. A second cage received air that flowed over healthy mice. The team then added hungry mosquitoes to the third cage and let them choose where to stay.
Seventy percent of the mosquitoes crammed into the cage getting air from the Zika-infected rodents, the scientists report online today in Cell. The distribution of insects was similarly uneven when the air came from rodents with dengue rather than Zika. However, the mosquitoes did not favor a particular cage when the researchers sent the air from the infected animals’ cages through a filter apparatus that trapped chemicals, suggesting that the odor of the sick mice was attracting the insects.
People with dengue also produce this seductive scent, the team’s experiments suggested. Scientists cleaned the armpits of healthy people and dengue patients with an absorbent material, isolated molecules that could become airborne, and applied them to filter paper. Mosquitoes preferred the bouquet of dengue patients.
By capturing and analyzing molecules from infected rodents, the researchers identified the ingredients of eau de Zika or dengue. The mice emitted greater amounts of 11 potential odorants when they became ill, and further tests showed that one of these molecules, acetophenone, was an attractant for mosquitoes. Rodents that were sick exhaled about 10 times more acetophenone than their uninfected counterparts. Dengue patients also emitted more of the molecule than healthy people, the researchers found.
Cheng and his colleagues have discovered a way in which viruses can increase their host’s release of acetophenone. Certain bacteria that inhabit the skin are the main source of acetophenone. Skin cells normally keep their numbers in check with a protein called RELMa that kills microbes. However, the scientists found that mice infected with Zika or dengue viruses produced much less RELMa, which could allow the bacteria to proliferate and change the animals’ scent.
The researchers tested this explanation by feeding mice isotretinoin, a vitamin A derivative that increases RELMa synthesis, and then counting how many mosquitoes bit the animals. The insects liked less mice that 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 discovered numerous odor molecules that attract A. aegypti mosquitoes to their victims, including lactic acid and ammonia. “It’s unclear how this compound fits with the known attractants.”
Still, the results could “revolutionize” disease diagnosis, says James Logan, a disease control specialist at the London School of Hygiene & Tropical Medicine who was part of the team that showed that malaria parasites change people’s skin chemistry. Today, a blood test is needed to determine whether a patient has Zika or dengue, and the results aren’t immediately available, he notes. An electronic nose that can detect acetophenone exhaled by a person can provide a diagnosis much faster and without a blood sample, says Logan. A spin-off company he founded is developing sensors that can identify malaria from body odor, and similar technology could work for Zika and dengue, he says.
Furthermore, the findings suggest “a new way” to combat these diseases by reducing human attractiveness to mosquitoes, says Cheng. One strategy he and his colleagues are now testing involves giving isotretinoin or related compounds to dengue patients.
