Being bit by a mosquito carrying dengue or Zika virus can make you sick. The infection can also make you even more attractive for other mosquitoes, new research finds.
It’s an itchy concern for anyone infected, but also poses a major risk to communities at large: Mosquitoes that aren’t already carrying the viruses could be more drawn to sick humans, become infected, and go on to infect more humans. The spread of dengue, in particular, is a threat, with about half the world’s population at risk and hundreds of millions of cases each year. Most cases are asymptomatic, but serious cases can lead to fever and vomiting, and in some instances, organ failure or death.
The study, published Thursday in Cell, identifies a specific scent emitted from both Zika- and dengue-infected mice that makes them more attractive to mosquitos than those without the viruses. It also points to a potential route to neutralize the olfactory flag.
“This is a highly, highly influential study,” said Nikolaos Vasilakis, a professor of pathology at the University of Texas Medical Branch in Galveston who was not involved with the research. “I’m pretty sure it’s going to foster or spin off several new lines of experimentation to get a better understanding of what’s happening in humans.”
In the experiments, performed at Tsinghua University in Beijing, mosquitos in a cage could enter a chamber with virus-infected mice or one with healthy mice. The mosquitos had no preference among the mice when the experimental group was newly infected, but on days four and six of infection, around 70% of the mosquitos flew to the infected group.
“An essential scientific question is how mosquitoes effectively orient to viremic hosts with a high frequency,” lead author Gong Cheng wrote in an email.
Body temperature, carbon dioxide levels, and scent are all known factors in attracting mosquitos to a host. The researchers isolated each factor in repeated experiments to systematically eliminate temperature and carbon dioxide and identify scent as the attractant. To determine exactly what caused the change in scent, they analyzed hundreds of potential volatile compounds emitted from the sick mice and narrowed it down to one, called acetophenone. The amount of acetophenone on the infected mice was found to be 10 times higher than on the uninfected ones.
“Regarding virus-induced changes in behavior, this study is like a unicorn because of how in-depth they were able to go on all these levels,” said Megan Wise de Valdez, an associate professor of biology at Texas A&M in San Antonio, who was also not involved. She said the study’s methodology was so rigorous she plans to teach it in the classroom.
Still, when it comes to results, “a mouse is a mouse is a mouse is a mouse,” said Vasilakis — meaning the stronger insights come from looking at humans. So the researchers took it a step further.
They applied acetophenone to human hands and found it had a similar effect in attracting mosquitos. And after finding that dengue patients were putting out higher levels of acetophenone than healthy people, they collected odors from the armpits of both and applied the scent extracts to filter paper. The perfumed papers were stuck to a human volunteer’s hand in the trapping chambers. Those with the odors of dengue patients attracted more mosquitos.
After pinpointing the cause of the increased attraction, the researchers tested a possible solution. They’d found that when viruses like Zika or dengue invade the body, they suppress a particular antimicrobial protein on the skin that controls acetophenone. Researchers were able to reactivate that protein and stop the overproduction of acetophenone by feeding the mice isotretinoin, a vitamin A derivative often used as acne medication. After that, mosquitos fed on the treated mice less than the untreated mice.
“If that holds in longitudinal studies, then there is hope that this is going to be an extremely effective tool in the arsenal that we have against infectious diseases,” said Vasilakis.
The researchers will focus their next studies on both the host — by testing potential treatments to suppress acetophenone in human dengue patients — and the vector, by searching for the genetic key in mosquitos that identifies and seeks the acetophenone, and attempting to remove it.
In the global effort to fight the viruses, this research lays new groundwork. But it will likely take years to decades before we have a solution as simple as a pill for patients to ward off hungry mosquitos.
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