One billion people in the world are infected every year!Professor Tsinghua discovered the secret of blocking such viruses

Author:Scientific network Time:2022.07.01

Text | "China Science News" trainee reporter Liu Runan

After reading the blog, Cheng Gong has been on the mosquito and mosquito media virus for nearly 15 years.

After studying more than 100,000 mosquitoes, there have always been problems in his mind: mosquitoes can quickly spread diseases such as malaria, dengue fever, and encephalitis. In just half a year, they can make a city epidemic rampant. It is understood that viruses transmitted through mosquitoes around the world can cause one billion people to be infected each year. "Why can they spread so fast?"

Recently, Cheng Gong, a professor at the School of Medicine of Tsinghua University, found the answer: human smell is a key factor in regulating mosquito behavior.

For mosquitoes, the unique odor emitted by the infected person seems to be a label against "biting me", which helps it locks the target in the vast sea of ​​people. Once he completes the blood -sucking and digestion, it quickly becomes a new source of infection.

Fortunately, Cheng Gong and others also discovered the "antidote" to deal with it: by regulating the skin microorganisms and changing the smell of the infected person, thereby affecting the sense of smell of mosquito. On June 30, the study boarded Cell magazine.

Plants are more "sweet" after being infected with viruses

It has been hundreds of years of research on mosquito media virus, but it is still not ideal to prevent control through drugs and vaccines. For the case of dengue fever, its vaccine has an ADE (antibody dependency enhancement) effect, that is, the vaccine not only failed to prevent virus infection, but also caused more serious symptoms of infection.

"In this case, we want to focus on blocking the transmission pathway. This does not need to control the transmission of all mosquito media viruses for each virus development vaccine, and to solve the problem of infection once and for all." Cheng Gong said.

For a long time, this idea only stayed at the conjecture stage, and there was no substantial progress.

Until 2019, in order to prepare for the annual invitation of the "Viruses Yearbook", Cheng Gong needs to consider a large number of literature materials.

He deeply learned that although the plants cannot move, they still suffer from various infectious diseases. 80%of plant viruses are spread by insects, which is consistent with the process of human and animals. Once the plant is infected by the virus, its smell will change, exuding a more "sweet" taste than normal plants, attracting more insects to eat.

At that time, Zhang Hongxin, a postdoctoral school of Tsinghua University, joined the laboratory. Before, she had made many beetles to eat leaves and found that beetles were masters of food finding food through odor.

Maybe this interaction may also exist between mosquito and bite objects?

"It may seem unrelated, and there is some coincidence in the underworld. When researching other fields can provide some support evidence and enlighten yourself, you will feel very excited and look forward to Verify it. "Cheng Gong told the" China Science News "," Maybe this is the stone of the ancients' other mountains, which can attack jade. "

Researchers use their arms olfactory measurement device to perform experiments. From right to left: Communication author Cheng Gong, the first author of the first author, Dr. Zhu Yibin and Dr. Zhang Hong.

Seeking blood can't, "mouse flavor temptation"

After spreading a series of viruses, do these annoying mosquitoes only love to find people and drink blood?

It's really not.

At present, there are more than 3600 kinds of mosquitoes, only Egyptian mosquito, white -patterned Iraqi mosquito (commonly known as "flower spots mosquito") and other love blood, others also prefer poultry blood, those who prefer cattle blood, prefer sparrow blood, etc. Wait, in short, "radish and cabbage, each has their own love".

In this way, Egyptian Mosquito and white -textured and mosquitoes have naturally become the most ideal experimental object of scientific researchers. In Cheng Gong's laboratory, a staff member who specializes in mosquitoes can contribute to the laboratory every day to contribute thousands of Egyptian and Iraqi mosquitoes.

How to solve the problem of so many mosquitoes, do you need to donate blood for staff?

Not suitable, not let them sweat and bleed. As the so -called "hunger", a few days after hungry mosquitoes, the mouse blood became a beautiful meal.

Because of this, the three cage olfactory measurement devices and arms olfactory measurement devices established by Cheng Gong and others can use mice as bait.

In the three cages olfactory measurement device, the box on the left is full of the "mice" of healthy mice, and the box on the right is full of the smell of dengue virus or Zika virus infection with mice. The researchers put 60 groups in a group. The mosquitoes were put in the box in the middle, and they flew into the box on the right without 20 minutes. These mosquitoes also have the same performance in the arms olfactory measurement device.

San cage smell measurement device

The mosquitoes in the laboratory alone are not enough to explain the problem, and they need to find some wild mosquitoes to assist in verification. In this way, it can only be caught by "human taste".

In the jungle with high temperature and humidity in the wild, I saw a staff member who was tightly wrapped in a small piece of skin on his arms, sitting and waiting for mosquitoes.

"Hey" mosquito

Once the mosquito stops, "咻 ~ ~", the person next to it quickly put it into the pocket with a mosquito rifle. This method is not broken. A little hesitant hesitated, and the mosquito's mouth was stabbed.

However, after the technical skills are pure, after a day, dozens or even hundreds of them are not a problem.

Studies have shown that "mice infected by dengue virus and Zika virus are significantly more attractive to Egyptian mosquito, white -patterned and mosquito. Story changes are the decisive factor that causes the host to attract mosquitoes. "Cheng Gong said.

Further research shows that after mosquito media infection, a mosquito can release a large number of volatile small molecules, phenyl, which can effectively activate the olfactory nervous system of mosquito and help mosquito to quickly discover the goals. How to remove the label of "Bite me"?

Animal experiment is done, is the same in human body?

At this time, Cheng Gong ushered in the biggest difficulty in the research: in 2020, the new crown pneumonia epidemic was outbreak and the border was blocked. As a typical input infectious disease, domestic infected people basically come from immigrants from tropical regions. Where to find patients? This caused Cheng Gong's headache.

He contacted the doctors in the county and city of Yunnan, and planned to "keep the plant and treat rabbits". This defender was half a year. It was not until May that Dehong Prefecture had a small amount of infection, and they quickly rushed to the past.

It is unrealistic to use patients to lead mosquitoes.

They have developed a convenient and effective method: with cylindrical magnetic beads, covering materials that can adsorb odors (polygenic siliconxane), which are the most prone to the three of the patients under the armpits, necks, and arms. The sweat is rolled for 10 minutes, then immersed in the orthopedane solution, and the "human taste" is transferred to the liquid.

At the same time, they also selected healthy people who live in the local area, the same age, and gender as the control group. The test results are satisfactory: dengue fever patients are more attractive to mosquitoes.

Subsequent mechanism research shows that dengue virus and Zika virus infection can inhibit the expression of RELM-ALPHA/RETN in the host's skin, so that the excessive appreciation of the skin spores that were originally suppressed, resulting in the label of the infected host to release the "bite me" label --Acetophenone.

Based on this, researchers have found that feeding a drug to infected mice -different vitamin acid, which can effectively help them eliminate this label. "This reminds that after oral drugs, mosquitoes cannot locate and discover the infection of the host through the phenylone released by the host, thereby blocking the transmission cycle of the virus." Cheng Gong told the China Science Journal.

Change "blocking" to "sparse"

Unfortunately, the skin microorganisms collected by the researchers failed to cultivate in the laboratory. Therefore, data such as changes in the skin microorganisms of the infected people are not presented in the research papers.

Due to the repetition of the domestic new crown epidemic, in recent years, the number of entry and exit has continued to be low, and there are very few patients with dengue fever. In Malaysia, Singapore, Vietnam, Myanmar and other countries, there have been many patients with an epidemic, with many patients.

"At present, we have completed the study of microorganisms in the skin of the infected and non -infected people in Malaysia. Next month, the clinical trial of alienation is about to be carried out. If it is smooth, it may be promoted in the future." Peronic acid has long been approved drugs, and this study is equivalent to adding an indication to it.

Considering it, from inspiration, animal tests, human test, to future clinical trials, Cheng Gong needs to pay at least 6 or 7 years of effort. This is not the brewing stage of asking questions and thinking directions in the early stage.

The reason for his persistence is that he hopes to change the research and prevention of mosquito media virus, and he hopes to become "blocking" into "sparse".

"Over the years, when a mosquito media infection occurs in a region, most of us are limited to the description of public health, such as the statistical infection rate, number of people, and so on. The large -scale use of insecticides that can kill the pesticides did not reduce mosquito media viruses. Instead, it has intensified. In the past 40 years, the incidence of dengue fever has increased by 30 times. "He said.

"So we need to truly understand that the basic principle of the mosquito media virus in nature? Why does it spread? Why can it spread quickly? The complex interconnection between the virus has many mysteries to be answered. "

It is these complicated effects and mysteries that make Cheng Gong very fascinating, and also give him the determination of not chasing hot spots and insisting on himself.

Since returning to China for 11 years since Yale University, he has said that he is not "high -yield", but he has devoted great efforts to each study. He hopes that each study can promote the field, and each job can answer a real scientific question.

"Then, mosquitoes are also 'victims'. Before it spreads the virus, it must be infected by itself. And it is not easy to find the blood vessels smoothly. It needs to be spines more than a dozen times in order to see the blood. "Cheng Gong said.

The people use food as the sky, as do the mosquitoes. It can live steadily but no longer "keen" to spread viruses to humans. Perhaps this is the best picture of the future.

Related thesis information:

DOI:

https://dx.doi.org/10.1016/j.cell.20222.05.016

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