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The Team at Tsinghua University reveals the reason for the rapid spread of mosquito-borne viruses – which people mosquitoes like to bite more

author:Xinhua

Itching, swelling, many people's summer memories, mosquitoes are a nasty presence. In addition, mosquitoes bring a variety of terrible mosquito-borne infectious diseases to people. In 2018, among the eight infectious diseases released by the World Health Organization that need urgent attention, Zika fever and Rift Valley fever were two fierce mosquito-borne viral infections.

In the vast sea of people, what kind of people are most attractive to mosquitoes?

The reporter learned from Tsinghua University that in a study just published in "Cell", the team of Professor Cheng Gong of the university's medical school revealed the cunning of mosquito arboviruses: mosquitoes do not randomly bite the host, and human odor is a key factor in regulating mosquito behavior.

"The olfactory nervous system of mosquitoes senses a characteristic odor molecule derived from the infected person, locates the infected person efficiently, and then bites and eats the blood with the virus, resulting in efficient transmission of the virus between the 'host-mosquito'." Cheng Gong said that the main source of human odor is skin microorganisms, and by regulating skin microorganisms, reshaping the odor of infected people can affect the olfactory perception of mosquitoes. The findings suggest that this finding provides a new strategy for interrupting the rapid spread of mosquito-borne viruses in nature.

Why are these people more favored by mosquitoes?

Relevant data show that there are hundreds of mosquito-borne viruses in nature, which can be carried by mosquitoes and transmitted to human and animal hosts, causing serious diseases such as viral encephalitis, meningitis and hemorrhagic fever. In the past 20 years, new and re-emerging mosquito-borne viruses, represented by dengue virus, Zika virus, chikungunya virus and West Nile virus, have been circulating around the world, causing billions of infections and hundreds of thousands of deaths every year.

Unfortunately, so far, most virulent mosquito-borne viruses have no effective vaccines and targeted therapeutic drugs, and the scientific community urgently needs to study the basic principles of the epidemic transmission of mosquito-borne viruses in nature and develop new prevention and control strategies to block the large-scale spread of viruses around the world.

"Mosquito arboviruses circulate between hosts and mosquitoes. In the viral cycle, mosquitoes need to find, locate, and bite infected people or animals to feed on blood that carries the virus. Subsequently, mosquitoes are equipped with the ability to carry and quickly transmit the virus. If a mosquito bites a non-infected person, the virus infection is not effectively acquired and the transmission cycle of the virus is interrupted. Cheng Gong said.

How do mosquitoes target people infected with the virus? Why are these people more "delicious" to mosquitoes? Scientists have long been working to unravel this mystery and find easy and effective ways to curb the rapid spread of the virus.

In the study by Cheng Gong's team, the researchers established two classical behavioral devices (three cage olfactory assay devices and two-arm olfactory assay devices) and found that mice infected with dengue virus and Zika virus were significantly more attractive 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 of host odor was the decisive factor that led to the attraction of mosquitoes to the infected host. Further research results show that mice can release a large number of volatile small molecules - acetophenone after mosquito arbovirus infection, which can effectively activate the olfactory nervous system of mosquitoes and enhance the behavior trend of mosquitoes to infected mice.

The researchers further collected odors from dengue patients and healthy volunteers and found that the odors of dengue patients showed greater appeal to the Aedes aegypti mosquito. Moreover, the odor content of dengue patients was also significantly higher than that of healthy volunteers. The researchers applied different concentrations of acetophenone to human arms for mosquito behavioral verification and found that increasing the amount of acetophenone in human odor significantly attracted mosquitoes.

The above tests 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?

Since acetophenone is the "culprit" that attracts mosquito bites, how does this "fragrance" that attracts mosquitoes come about?

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, which is a typical bacterial metabolite. After removing the symbiotic microorganisms from the skin, infected mice lose 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 host skin surface Bacillus bacteria, which have the ability to metabolize 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 phenyl ketone release capacity of infected people, and thus significantly improves the behavior trend of mosquitoes to infected hosts.

Subsequently, the researchers performed transcriptome sequencing analysis of skin tissues in virus-infected and non-infected mice. The results showed that dengue virus and Zika virus infections can overproliferate bacillus otherwise suppressed skin by inhibiting the expression of inhibitory-like molecules or specific immune molecules such as immune molecules in the host skin, resulting in an increase in the release of acetophenone from the infected host.

Subsequently, the researchers fed a vitamin A derivative, isotretinoin, a widely used clinical treatment for dermatological diseases, into mice infected with dengue virus and Zika virus. The results showed that the above operation can effectively restore the expression of specific immune molecules in the skin of infected mice, and inhibit the release of acetophenone by inhibiting the proliferation of Bacillus in the skin of the infected host. Therefore, after oral administration of isotretinoin by an infected host, mosquitoes are unable to locate and detect the infected host through the host's acetophenone, thereby interrupting the transmission cycle of the virus.

How to stop the rapid spread of mosquito-borne viruses

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.

Since in the early stage of the epidemic of mosquito-borne virus infectious diseases, the proportion of infected people in the population is only one-thousandth or even lower, so the research team speculates that after the infected person takes oral vitamin A drugs, mosquitoes cannot distinguish infected people from non-infected people by the smell of acetophenone, which can greatly reduce the probability of mosquitoes eating the blood of infected people and infecting, so that mosquito-borne viruses cannot efficiently establish a "host-mosquito" transmission cycle process in nature.

Based on this, the research team proposed a new strategy for the prevention and control of mosquito-borne virus infectious diseases: in the 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, reshaping the volatile odor of microorganisms on the skin of infected people, greatly reducing the cycle efficiency of mosquito-borne virus transmission, and effectively preventing mosquitoes from carrying and transmitting viruses. Based on the above findings, vitamin A or related drugs can be supplemented to specific infected people to avoid the large-scale transmission of mosquito-borne virus infectious diseases.

It is reported that at present, Cheng Gong's team has completed the study of skin microbial changes in infected and non-infected people in Malaysia, and will soon carry out clinical trials of isotretinoin. In the future, it is expected to promote the application of its research results. (Reporter Deng Hui Correspondent Zhang Hong)

Source: Guangming Daily

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