Viruses that cause Zika fever and dengue cannot be transmitted from person to person on their own – they must travel to a stop in a mosquito. A new study shows how they welcome these walks: they make their victims smell more attractive to blood-sucking bugs.
This is “a big step forward,” said mosquito neurologist Laura Duvall of Columbia University, who is not involved in the study. The study shows that “infection with these mosquito-borne viruses can change the way some people smell… to make them more likely to be bitten.”
A person can emit a different body odor when he is ill, especially with an infection. Patients with COVID-19, for example, secrete a distinctive mixture of molecules that dogs and electronic “noses” can detect. Similarly, malaria parasites alter the odor of human hosts, which makes them irresistible to mosquitoes.
It is not known whether the viruses that cause Zika fever and dengue fever, which infect up to 400 million people each year, also interfere with the odor. These pathogens travel from person to person Temples of the Egyptians mosquitoes, which also transmit yellow fever and chikungunya viruses.
To determine whether insects were addicted to individuals with Zika or dengue, microbiologist Gong Cheng of Tsinghua University and colleagues created three interconnected cells for a mouse experiment. In a cage, they released air that was dispersed through mice infected with the Zika virus. A second cell receives air that flows over healthy mice. The team then added hungry mosquitoes to the third cage and left them to choose where to hang.
Seventy percent of mosquitoes congregate in the cage, receiving air from Zika-infected rodents.,, scientists report online today at cell. The distribution of insects was evenly sloping when the air came from dengue rodents, not Zika. However, mosquitoes did not prefer a specific cage when the researchers sent air from the cells of infected animals through a filter apparatus that traps chemicals, suggesting that the smell of sick mice attracts insects.
People with dengue also produce this tempting scent, the team’s experiments suggest. Scientists wipe the armpits of healthy people and patients with dengue fever with absorbent material, isolate molecules that can be carried in the air, and apply them to filter paper. Mosquitoes preferred the bouquet of dengue sufferers.
By capturing and analyzing molecules derived from infected rodents, the researchers identified the ingredients in water of Zika or dengue. Mice emit larger amounts of 11 potential odors when they become ill, and further tests show that one of these molecules, acetophenone, is a mosquito attractant. Rodents that were sick excreted about 10 times more acetophenone than their uninfected counterparts. Dengue patients also release more of the molecule than healthy people, the researchers found.
Cheng and his colleagues discovered a way in which viruses could increase their host’s release of acetophenone. Some bacteria that inhabit the skin are the main source of acetophenone. Skin cells usually keep their numbers under control with a protein called RELMa, which kills germs. However, the researchers found that mice infected with Zika or dengue viruses released much less RELMa, which could allow the bacteria to multiply and change the animal’s odor.
The researchers tested this explanation by feeding mice with isotretinoin, a derivative of vitamin A that increases RELMa synthesis, and then calculating how many mosquitoes had bitten the animals. Insects were less fond of mice that consumed isotretinoin.
“It’s a very compelling document,” said Ring Carde of the University of California, Riverside, who studies chemical ecology and insect behavior. But he warns that other research teams have found a number of odor molecules that attract A. aegypti mosquitoes of their victims, including lactic acid and ammonia. “It’s not clear how this compound fits into the known attractants.”
However, the results could “revolutionize” disease diagnosis, said James Logan, a disease control specialist at the London School of Hygiene and Tropical Medicine who was part of a team that showed that malaria parasites alter the chemistry of human skin. A blood test is needed today to determine if the patient has Zika fever or dengue, and the results are not immediately available, he said. An electronic nose that can detect acetophenone secreted by a person can provide a diagnosis much faster and without a blood sample, Logan said. A founding company is developing sensors that can identify malaria from body odor, and similar technology can work for Zika and dengue, he says.
In addition, the findings suggest a “new way” to fight these diseases by reducing human attractiveness to mosquitoes, Cheng said. One strategy he and colleagues are now testing involves giving isotretinoin or related compounds to patients with dengue fever.