Smell can be a powerful motivator. The scent of freshly baked cookies can compel a person to come to the kitchen, while a musky scent can lure a date. In the mosquito world, an irresistible smell is the one produced by two dangerous viruses after hijacking a human body, according to a new study.
The viruses that cause Zika and dengue alter the smell of their hosts, making them more susceptible to mosquito bites, researchers say. The discovery was announced Wednesday in the journal Cell and is the result of experiments in mice and humans.
Scientists have also identified a potential way to block this smell and stop the spread of the disease, using a drug already familiar to acne sufferers, isotretinoin, also known by the trade name Accutane. .
“In some countries, these mosquito-borne diseases are widespread,” said co-author Penghua Wang, assistant professor at UConn Health, the University of Connecticut School of Medicine and Medical Center. “In the long term, if this drug really works, 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 is made by bacteria that grows on the skin, but normally the skin secretes a protein that holds it there. However, this study suggests that Zika and dengue suppress production of this essential protein, allowing bacteria to grow faster and more acetophenone to emerge.
The result is an odor that attracts mosquitoes and propels the cycle of infection forward. While people in tropical and subtropical regions – where these viruses thrive and are a major public health concern – are susceptible to mosquito bites in general, this smell increases the chances of mosquitoes 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 transmit the virus to a healthy mosquito. Newly infected mosquitoes may continue to do more damage.
Researchers have previously found 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 fever.
Dengue fever is a viral infection caused by four closely related viruses. These viruses are spread through the bites of two types of mosquitoes. While half of the world’s population is at risk of developing dengue fever, more than 80% of cases are usually mild and asymptomatic, according to the World Health Organization. However, it can be more serious. While scientists report that dengue fever cases may be undercounted due to Covid-19, on average it is 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 types of mosquitoes. Most people infected with Zika do not develop symptoms, and those who do suffer from fever, conjunctivitis and neurological complications. Zika virus infection during pregnancy can also lead to a birth defect called microcephaly.
There is no specific vaccine or medication for the Zika virus. The dengue vaccine is only recommended for children aged 9 to 16 who have already been infected – the aim is to prevent severe dengue in the future.
The new study uncovered a previously unknown step in the spread of Zika and dengue fever. These infections can alter a person’s smell, and that smell makes them more attractive to mosquitoes, which means they are more likely to be bitten. For now, it’s unclear whether this process is the result of evolution or chance, Wang said.
The study team infected mice with Zika and dengue fever to examine the link between smell and mosquitoes. They then set up three interconnected cages, dividing healthy mice, infected mice and mosquitoes. Each group of viruses was assessed separately. However, the results were very similar: about 70% of mosquitoes chose to be in the trap chamber with infected mice.
The scientists also recruited dengue patients from a hospital in China and healthy volunteers. They collected the volunteers’ odors through armpit swabs, then extracted and transferred the compounds causing those odors to a piece of filter paper. Then a new, seemingly unpleasant experience began: a paper with the smell of a healthy or infected person was tied to one volunteer’s hand, while an odorless paper was tied to his other hand. Both hands were exposed for 30 minutes to mosquitoes.
Overwhelmingly, hands covered in the smell of dengue patients were more attractive to mosquitoes than the other options.
When the researchers assessed the skin of the study participants, they found that the dengue patients had a much higher release of acetophenone than the other participants. Meanwhile, mice infected with Zika or dengue fever also produced 10 times more acetophenone than healthy mice. Smell remained the primary driver of mosquito bites even after scientists controlled for other attractants, such as body heat and carbon dioxide levels.
After scientists determined that mice infected with Zika or dengue fever produced less of the protein that kills the bacteria responsible for acetophenone, they set out to find a solution. They fed the mice isotretinoin, a derivative of vitamin A and a known acne drug. This changed the composition of bacteria on the mice’s skin and reduced acetophenone levels. In turn, the mosquitoes were less interested in eating on the treated mice.
Because mouse skin is different from human skin, the team now wants to see if the same treatment would work for humans. They also want to expand the study more generally and assess 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 prevalence of the virus and the disease burden,” Wang said. ” But this will take time. This potential treatment will not kill mosquitoes, but it may reduce transmission. »
In the distant future, these results could also inspire 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 smell-related process.
“We could try to silence the mosquito’s olfactory neurons,” Wang said. “These mosquitoes would still be able to reproduce, but they might be less sensitive to human signals. They may be less interested in biting humans.
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