Mosquito-borne virus is one of the most widely spread and most harmful viruses in the world. It is mainly carried by mosquitoes and transmitted to human and animal hosts. It can cause serious diseases such as viral encephalitis, meningitis and hemorrhagic fever. The virus can infect billions of people and kill hundreds of thousands of people every year.

According to relevant national governments and media reports, dengue fever will once again break out on a large scale in Brazil, Singapore, Malaysia and other countries in 2022. As of May this year, more than 650,000 people have been infected and hospitalized.

In order to develop new prevention and control strategies and block the large-scale spread of mosquito-borne viruses around the world, on June 30, the team of Professor Cheng Gong from Tsinghua University School of Medicine published an online publication entitled “Cell”, an international academic journal. An odorant volatile mediated by skin commensal microbes promotes mosquito attraction to flavivirus-infected hosts”.

The study’s corresponding author, Cheng Gong, a professor of microbiology and infectious diseases at Tsinghua University School of Medicine, told The Paper (www.thepaper.cn) that the study found that human odor is a key factor in regulating mosquito behavior. By modulating skin microbes and reshaping the odor of an infected person, the olfactory perception of mosquitoes can be affected. Based on this, they further proposed a method for regulating host odor through skin microbes and blocking the rapid spread of mosquito-borne viruses in nature.

Breaking the cycle of mosquito-borne virus transmission

In the transmission cycle of mosquito-borne viruses, mosquitoes need to find, locate, and bite an infected person or animal, feeding on virus-laden blood. Only then can mosquitoes have the ability to carry and spread the virus quickly. If the mosquito bites a non-infected person, the virus infection will not be effectively acquired, and the transmission cycle of the virus will be interrupted.

Cheng Gong told The Paper that the observation found that in the early stage of the mosquito-borne virus outbreak, the proportion of infected people in the population was not high (only 1 in 1,000 or even lower). Mosquitoes can choose to bite infected people in the crowd, thereby accelerating the spread of the virus and causing outbreaks. It can be seen that how mosquitoes can effectively locate and infect the host and obtain the virus is the main rate-limiting step for the virus to complete the “host-mosquito” transmission cycle.

Mosquito-borne virus “host-mosquito” transmission cycle.

This raises a long-standing scientific question: how do mosquitoes locate infected people in the vast crowd? If we can clarify this problem, we can explain the reasons for the rapid spread of mosquito-borne viruses in nature, and further find simple and effective methods to curb the rapid spread of the virus. In this study, the researchers established two sets of classical behavioral devices – a three-cage olfactory measurement device and a dual-arm olfactory measurement device, and found that mice infected with dengue virus and Zika virus were significantly more attracted to Aedes aegypti. and Aedes albopictus.

Subsequently, the researchers analyzed the body temperature, carbon dioxide release and volatile odor of the virus-infected mice, and found that the change in the host’s odor is the decisive factor that causes the infected host to attract mosquitoes. Further research results show that mice can release a large amount of a volatile small molecule – acetophenone after mosquito-borne virus infection. Acetophenone can effectively activate the mosquito’s olfactory nervous system and enhance the mosquito’s response to infected mice. behavior trends.

The researchers collected the odor of dengue patients and healthy volunteers and found that the odor of dengue patients showed a stronger attraction to Aedes aegypti, and the odor of dengue patients was also significantly higher than that of healthy volunteers.

The researchers found that the acetophenone released by humans or animals mainly comes from skin symbiotic microorganisms on the body surface. After the skin commensal microbes were removed, the infected mice lost their stronger attraction to mosquitoes. Further studies have shown that dengue virus and Zika virus infection can lead to a significant increase in the abundance of Bacillus spp. bacteria on the host skin surface, while Bacillus dermatophytes has the ability to metabolize and produce a large amount of acetophenone.

So far, the researchers have revealed the reason why mosquito-borne virus infected people attract mosquito bites: virus infection increases the proportion of specific bacteria in human skin, significantly increases the ability of infected people to release acetophenone, and thus significantly improves the mosquito’s ability to infect the host. behavioral trends.

The results of the study showed that if the mice infected with dengue virus and Zika virus were fed a vitamin A derivative, isotretinoin (a widely used clinical drug for skin diseases), the infection could be suppressed. The proliferation of Bacillus in the host skin inhibits the release of acetophenone from the infected host. Therefore, after the infected host takes isotretinoin orally, the mosquito cannot locate and find the infected host through the host’s acetophenone, thereby blocking the virus transmission cycle.

New ideas for prevention and control of mosquito-borne viruses

In the past 20 years, emerging and re-emerging mosquito-borne viruses, represented by dengue virus, Zika virus, chikungunya virus, and West Nile virus, have been prevalent around the world, infecting billions of people and causing dozens of infections every year. Thousands died. Taking dengue virus as an example, about 2.5 billion people in the world live in dengue virus-endemic areas, and about 390 million people are infected or reinfected with dengue virus every year, of which 500,000 to 1 million people are admitted to hospital for treatment, and Dengue fever has spread in more than 100 countries and regions around the world.

However, due to the special pathogenic mechanism of important mosquito-borne viruses such as dengue virus, the antibodies produced after infection or immunization have the effect of enhancing infection (antibody-dependent enhancement effect, or ADE effect), which makes traditional infectious disease prevention (vaccine). And treatment (drug) strategy development is hindered. So far, there are no effective vaccines and targeted treatments for most virulent mosquito-borne viruses.

Based on the findings of the above research, Cheng Gong’s team proposed a new idea for the prevention and control of mosquito-borne viruses: the rapid spread of mosquito-borne viruses can be blocked by regulating human body odor.

Acetophenone released by skin symbiotic microorganisms regulates the attraction of infected hosts to mosquitoes, and inhibiting the release of acetophenone mediated by host skin microorganisms can effectively block the transmission cycle of mosquito-borne viruses.

Since in the early stage of the epidemic of mosquito-borne virus infectious diseases, the proportion of infected people in the population was only one thousandth or even lower, so the research team speculated that after the infected people took vitamin A drugs, mosquitoes could not pass the smell of acetophenone. Distinguishing infected people from non-infected people can greatly reduce the probability of mosquitoes feeding on the blood of infected people and infecting them, so that mosquito-borne viruses cannot efficiently establish a “host-mosquito” transmission cycle in nature. Based on this, the research team proposed a new strategy to prevent and control mosquito-borne virus infectious diseases: in epidemic areas where mosquito-borne virus infectious diseases such as dengue fever and Zika fever are prevalent, vitamin A or related drugs can be widely supplemented to infected people to reshape the infection. The odor of the skin microorganisms volatilizes, greatly reduces the circulation efficiency of mosquito-borne virus transmission, effectively prevents mosquitoes from carrying and spreading the virus, and avoids the large-scale spread of mosquito-borne virus infectious diseases.

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