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In the eyes of mosquitoes, why are you so delicious?

author:Bright Net

Speaking of the most annoying animals of summer

The answer for many people must be mosquitoes

In addition to unbearable itching and lumps

Mosquitoes bring to people

There are also a variety of terrible mosquito-borne infectious diseases

In the middle of a vast sea of people

What kind of people attract mosquitoes the most?

In one article just published in

The Cell study

The team of Professor Cheng Gong of Tsinghua University School of Medicine

This reveals the cunning of mosquito-borne viruses

In 2018, two of the eight infectious diseases of urgent concern published by the World Health Organization included two virulent mosquito-borne virus infections (Zika fever and Rift Valley fever). Mosquito-borne viral infections, such as dengue, Zika, chikungunya, Rift Valley fever and West Nile encephalitis, pose serious challenges to global public health security.

Taking dengue virus as an example, the World Health Organization estimates that about 390 million people are infected or repeatedly infected with dengue virus every year, resulting in 500,000 to 1 million people being hospitalized. Due to the complex pathogenic mechanism of mosquito-borne viruses, most virulent mosquito-borne viruses still lack effective vaccines and targeted therapeutic drugs. Therefore, the scientific community urgently needs to conduct more in-depth research on the transmission mechanism of mosquito-borne viruses to provide new ideas for the prevention and control of mosquito-borne virus transmission.

You may have been curious about the question: Why do some people attract mosquito bites more? Is the body temperature higher? More carbon dioxide released? Or more sweat? The study found that human odor is a key factor in regulating mosquito behavior.

Why are you more delicious in the eyes of mosquitoes?

In the vast sea of people, mosquitoes do not randomly bite the host, they always seem to be able to accurately locate those who are infected with mosquito arboviruses. So, how do mosquitoes target people infected with the virus? Why are these people more "delicious" to mosquitoes?

Professor Cheng Gong's team at Tsinghua University School of Medicine revealed that the virus reshapes the odor of infected people by changing the skin microorganisms of the human body and affects the olfactory perception of mosquitoes. The discovery also provides a new strategy for stopping the rapid spread of mosquito-borne viruses in nature.

In the eyes of mosquitoes, why are you so delicious?

In this study, Professor Cheng Gong's team first set up three cage olfactory measuring devices, using mice as infection hosts and Aedes aegypti mosquitoes as infection vectors to control the experiment. It was found that mosquito-borne virus-infected mice can release a large number of volatile small molecules - acetophenone, which can effectively activate the olfactory nervous system of mosquitoes to affect the olfactory perception of mosquitoes.

In the eyes of mosquitoes, why are you so delicious?

Three-cage olfactory measuring device

Subsequently, the researchers further collected odors from dengue patients and healthy volunteers and found that the odors of dengue patients showed a stronger attraction to Aedes aegypti mosquitoes. Interestingly, the scent of dengue patients was also significantly higher in acetophenone levels than in healthy volunteers. When the researchers applied different concentrations of acetophenone to human arms for behavioral verification of mosquitoes, the results showed that arms with higher concentrations of acetophenone were more likely to attract mosquitoes. The above findings show that dengue patients have greatly improved their attractiveness to mosquitoes due to the release of large amounts of acetophenone to change their odor, attract mosquito bites, and accelerate the spread of the virus.

How does the "scent" that attracts mosquitoes is generated?

The question is, how do these viruses manipulate the host to produce more acetophenone?

The researchers found that the acetophenone released by humans or animals is mainly derived from the skin symbiotic microorganisms on the surface of the body, and the infection of dengue and Zika viruses can lead to a significant increase in the abundance of bacteria on the surface of the host skin, and this bacterium has the ability to metabolize and produce large amounts of acetophenone.

So far, the researchers have revealed the reason why mosquito-borne virus-infected people attract mosquito bites: viral infection increases the proportion of specific bacteria in human skin, significantly improves the acetophenone release capacity of infected people, and thus significantly improves the attractiveness of infected hosts to mosquitoes.

The research team is evaluating the mosquito's behavior through an olfactory assay device. From left to right, dr. Hong Zhang, co-first author, Yibin Zhu, assistant researcher, and corresponding author Professor Cheng Gong. (Image source: Xuan Guo)

Subsequently, to target key genes involved in the process, the researchers also performed RNA-Seq sequencing analysis of skin tissue in virally infected and non-infected mice. Dengue virus and Zika virus infections were found to overproliferate bacillus otherwise suppressed skin by inhibiting the expression of specific immune factors in the host skin, resulting in an increase in the release of acetophenone from the infected host.

In the latest study, the team fed a vitamin A derivative, isotretinoin, to dengue and Zika virus-infected mice. This is a clinically widely used dermatological drug that, after being taken in mice, effectively inhibits the proliferation of bacillus in the skin of the infected host, thereby limiting the release of special human odors. Therefore, after the infection of the host isotretinoin, the mosquitoes are unable to locate and infect the host by the host's odor, thus blocking the transmission cycle of the virus.

In the eyes of mosquitoes, why are you so delicious?

Supplementation with vitamin A drugs can reshape the release of acetophenone from the skin of infected individuals, reducing the efficiency of mosquito vector virus transmission cycles. (Image source: Courtesy of the research team)

How to get rid of the "come bite me" label?

Based on the above findings, the researchers proposed a new mosquito arbovirus prevention and control idea: it can block the rapid spread of mosquito arbovirus by regulating human odor. Extensive vitamin A or related drugs supplementation for infected people in endemic areas where mosquito-borne viral infections are endemic is expected to be a new strategy to avoid large-scale epidemics of mosquito-borne viral infections.

Professor Cheng Gong said: "At present, we have completed the study of skin microbial changes in infected and non-infected people in Malaysia. Next month, a clinical trial of isotretinoin will be conducted, and if it goes well, it is possible to promote its application in the future. Cheng Gong introduced that isotretinoin has long been an approved drug, and this study is equivalent to adding an indication to it.

"For many years, when mosquito-borne virus infections occurred in an area, we mostly limited ourselves to public health descriptions, such as counting infection rates, numbers of people, and so on. The solution is to 'extinguish it', people have developed a variety of insecticides, but the large-scale use of insecticides has not reduced the mosquito arbovirus, it has intensified, and the incidence of dengue fever has increased by 30 times in the past 40 years. "So we need to really understand, what is the basic principle of the mosquito vector virus transmission cycle in nature?" Why does it spread? Why is it so fast? This is the most basic and simple scientific problem, but it contains the complex interaction between humans, mosquitoes and viruses, and there are many mysteries to be answered. ”

It is these complex roles and mysteries that make Cheng Gong very fascinated, and also give him the determination not to chase hot spots and insist on himself. At present, researchers have initiated studies on the effects of other mosquito-borne virus infection hosts on mosquito behavior. It is believed that these studies will provide a new and powerful weapon for curbing the spread of more mosquito-borne diseases.

参考资料:[1] Hong Zhang et al., A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness. Cell (2022). DOI: 10.1016/j.cell.2022.05.016

Transferred from Tsinghua University

Source: School Komsomol

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