As if the Zika and dengue fever viruses weren’t bad enough on their own, they also have a nasty secondary effect: they get your body to produce a chemical that draws in even more mosquitoes. It’s a mechanism through which the virus helps the mosquitoes find more animals to bite — and in doing so, they also help the viruses spread to new hosts. But this may also help us fight these pathogens.

Zika and dengue are two diseases spread by mosquitoes in tropical areas around the world, and sometimes, they make their way into subtropical areas such as the southeastern US. The viruses require mosquitoes to spread — if the mosquitoes were to disappear or if they would stop spreading the pathogens, then the viruses would have no chance to survive as they would have no vector of transmission.

But even in areas where these mosquitoes exist, only relatively few people are infected, so how are these viruses so successful?

Dengue fever, for instance, cannot be passed from person to person. So in order for the virus to spread, it needs to pass itself to as many mosquitoes as possible, which then pass it on to humans (or other mammals). This means that from the virus’ perspective, you want to infect a human, and then other mosquitoes bite that exact human again. Dr. Gong Cheng of the School of Medicine at Tsinghua University explained in an email:

“Mosquitoes need to actively find, and then incidentally feed on infected humans or animals to acquire infectious viral particles circulating in the host blood. The viruses subsequently establish an infection in the vectors, thereby enabling them to become competent to transmit viruses to naive hosts through blood-feeding. However, the absolute number of infected individuals is very low. The ratio of infected individuals might be 1/1000, even lower, in the host population. Mosquitoes need to actively seek and feed on a viremic host to acquire infectious viral particles. Therefore, an essential scientific question is how mosquitoes effectively orient to infected hosts with a high frequency?”

A joint team including researchers from the US and China suspected that these viruses may be doing something to change their hosts’ scent. Mosquitoes rely on their sense of smell to detect hosts and survive in general, so if you’d want to attract mosquitoes to a specific host, sending out a signal for their sense of smell seems like the way to go. It’s not as unlikely as it sounds — researchers have observed it in nature before.

“Some plant viruses can manipulate their hosts to release specific volatile organic compounds that are attractive to their insect vectors compared with healthy plant hosts, thereby enhancing the probability of virus transmission,” Gong told ZME Science.

To first test this hypothesis, the team tested whether mosquitoes preferred mice that were infected with one of these two viruses — and they did. They then analyzed the molecules on the skin of infected and healthy mice to see what was different. They found that one molecule, acetophenone, was especially attractive to mosquitoes. When they applied it to the hands of human volunteers, mosquitoes were once again drawn to it.

“We observed that Aedes mosquitoes [which transmit dengue and Zika] preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people,” Gong explains.

“Here, we demonstrate that mosquito-transmitted flaviviruses [a group that includes Zika and dengueviruses] can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness,” the researcher adds.

The study could also have practical applications. For instance, researchers are now carrying out another study in which people infected by these viruses take vitamin A, which is expected to disrupt this cycle of producing mosquito-attracting acetophenone. The team is also working on generating a genetically modified mosquito that isn’t attracted to acetophenone. This way, mosquitoes would not be more drawn to infected humans, and in turn, the viruses will have a much harder time spreading to any new hosts.

“We provide a potential strategy for disease control: manipulation of host odors. This may act as a strategy to comprehensively control mosquito-borne flaviviral diseases (not just for dengue),” Gong concludes.

Journal Reference: Cell, Zhang & Zhu et al. “A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness” https://www.cell.com/cell/fulltext/S0092-8674(22)00641-9