Smell can be a powerful motivator. The fragrance of freshly baked cookies may compel a person to come to the kitchen, while a musky perfume might entice a date. In the mosquito universe, an irresistible scent is one produced by two dangerous viruses after hijacking a human body, a new study found.
The viruses that cause Zika and dengue fever alter how their hosts smell, making them more likely to be bitten by mosquitoes, according to researchers. The discovery was announced Wednesday in the journal Cell and is the result of experiments on both mice and people.
The scientists also identified a potential way to block this scent and stop the spread of the disease, using a medication already known to people struggling with acne, isotretinoin, also known by the trade name Accutane.
“In some countries, these mosquito-transmitted diseases are very prominent,” said co-author Penghua Wang, an assistant professor at UConn Health, the University of Connecticut’s school of medicine and medical center. “In the long run, if this medication really works, then people may have a way to prevent or at least reduce this burden.”
The smell is linked to high levels of a compound called acetophenone, described by the study authors as a “potent attractant” for mosquitoes. It’s made by a bacteria that grows on skin, but normally skin secretes a protein that restrains it. However, this study suggests Zika and dengue suppress the production of this critical protein, allowing the bacteria to grow faster and for more acetophenone to emerge.
This results in a scent that attracts mosquitoes and propels the cycle of infection forward. While people in tropical and subtropical areas — where these viruses thrive and are a leading public health concern — are likely to get bit by mosquitoes generally, this scent increases the odds that mosquitoes are biting infected individuals.
Vectors like mosquitoes help viruses survive. When an infected mosquito bites a healthy person, it can transmit a virus. An infected person, meanwhile, can spread the virus to a healthy mosquito. Newly infected mosquitoes can go on to do more damage.
Researchers previously discovered that malaria can alter the smell of its host, which in turn attracts mosquitoes. This suggested to the new study authors that it was worth investigating whether the same was true for Zika and dengue.
Dengue is a viral infection caused by four closely related viruses. These viruses spread through the bites of two types of mosquitoes. While half of the world’s population is at risk of developing dengue, over 80% of cases are generally mild and asymptomatic, according to the World Health Organization. However, it can be more severe. While scientists report dengue cases may be undercounted because of Covid-19, on average it’s known to cause around 20,000 deaths each year.
Zika belongs to the same family of viruses as dengue and is transmitted by the same kinds of mosquitoes. Most people with a Zika infection do not develop symptoms, and those who do experience ailments like fever, conjunctivitis and neurological complications. A Zika virus infection during pregnancy can also result in a birth defect called microcephaly.
There is no specific vaccine or medicine for Zika virus. The dengue vaccine is only recommended for children between the ages of 9 and 16 who have already been infected — the aim is to prevent severe dengue in the future.
The new study discovered a previously unknown step in the spread of Zika and dengue. These infections can change the way a person smells, and this scent makes them more attractive to mosquitoes, meaning they’re more likely to be bitten. For now, it’s unclear whether or not this process is the result of evolution or chance, Wang said.
The study team infected mice with Zika and dengue to examine the link between scent and mosquitoes. They then set up three interconnected cages, dividing healthy mice, infected mice and mosquitoes. Each virus group was evaluated separately. However, the results were very similar: Around 70% of the mosquitoes chose to be in the trapping chamber with infected mice.
The scientists also recruited dengue fever patients from a hospital in China and healthy volunteers. They collected the volunteers’ odors through armpit swabs and then extracted and transferred the compounds causing those smells to a piece of filter paper. Then a new seemingly unpleasant experiment began: A paper with the scent of either a healthy or infected person was attached to a volunteer’s hand, while an odorless paper was attached to their other hand. Both hands were exposed for 30 minutes to mosquitoes.
Overwhelmingly, the hands covered in the scent of dengue patients were more attractive to mosquitoes than the other options.
When the researchers evaluated the skin of the study participants, they found that the dengue patients showed a much higher emission of acetophenone than the other participants. Meanwhile, mice infected with Zika or dengue also produced 10 times more acetophenone than healthy mice. Scent remained the primary driver of mosquito bites even after scientists controlled for other attractants, like body heat and levels of carbon dioxide.
After the scientists determined that mice infected with Zika or dengue produced less of the protein that kills the acetophenone-causing bacteria, they set out to find a solution. They fed the mice isotretinoin, a derivative of vitamin A and a known acne medication. This changed the bacteria composition on the skin of the mice and reduced levels of acetophenone. In turn, the mosquitoes were less interested in dining on the treated mice.
Because mouse skin is different than human skin, the team now wants to see whether the same treatment would work for people. They also want to expand the study more generally and evaluate more human patients with dengue and Zika — this study only included 10 dengue patients. An effort is underway to recreate this study with a large sample of people in Malaysia.
“Overall, the goal is to reduce the virus prevalence and the disease burden,” Wang said. “But this will take some time. This potential treatment will not kill mosquitoes, but it may reduce transmission.”
In the far future, these results could also inspire the genetic editing of mosquitoes, Wang said. Other scientists are already experimenting with CRISPR to spread a mutation that blocks female reproduction. Scientists could also use CRISPR to interrupt this process linked to scent.
“We could try to silence the mosquito’s olfactory neurons,” Wang said. “Those mosquitoes would still be able to reproduce, but they may be less responsive to human cues. They may be less interested in biting humans.”