This article was written in 2017:
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13 years of unremitting pursuit of Chinese scientists to find the source of SARS virus
CCTV News Client CCTV News Client December 29, 2017 14:06A-A +
In 2002, the SARS epidemic was first discovered in Guangdong, China, and gradually spread to Southeast Asia and the world, triggering a global epidemic of infectious diseases. Fifteen years have passed since the first reported case of SARS in December 2002. Where is the source of the SARS virus? Recently, a scientific research result attracted the attention of the scientific community: experts from the Wuhan Institute of Virology, Chinese Academy of Sciences, found a natural gene bank of bat SARS coronavirus in Yunnan, China, and research revealed the possible recombination origin of SARS virus.
The SARS epidemic broke out in 2002. Two years later, that is, from 2004, the research team began to search for the source of the epidemic. This finding was 13 years. How was the host of the virus source locked on the bat? Finding a possible recombination origin of the SARS virus does it mean that the source of the SARS virus has been found? Today's story, we approached this scientific research team to reveal the secret of the source of the SARS virus and explore the scientific process behind the search for the "SARS" virus source.
Atypical pneumonia SARS, or Severe Acute Respiratory Syndrome, has been published by the WHO. From the end of 2002 to August 2003, SARS affected 32 countries and regions. There were 8422 infections and 916 deaths worldwide, with an average mortality rate of 10.8%. When the deadly epidemic finally subsided in 2004, research into the origin of the unknown virus began immediately.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences, and her new virus research team, also started the research on the source of SARS virus at this time.
Shi Zhengli, a researcher at the Wuhan Institute of Virology of the Chinese Academy of Sciences, will ask if there is a relative, saying that SARS is gone, what's the point of doing this thing? It ’s ridiculous, it ’s possible (disease) that it will never come, but I think we do a lot of work, and if one of your jobs can prevent the outbreak of disease, I think we are very meaningful.
Soon, researchers detected SARS coronavirus from civets on the wildlife market. However, further experiments found that although the civet was a direct source of infection, it did not seem to be the "originator".
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: Is the most direct source of infection the most fundamental source? This is not necessarily the case. In order to find the source of the virus, we need to find its natural host. Only by finding its source can we fundamentally prevent this disease.
Assistant researcher Hu Ben is responsible for the genetic evolution of the virus. The natural host he mentioned must carry the virus for a long period of time without causing disease. In addition, under natural conditions, these natural host animals must have a certain group infection rate. However, investigations of farms and wild civets turned out to be surprising.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: Both wild civet and farm civet are not infected with SARS virus, and if you artificially infect the civet with this SARS virus in the laboratory, it will also get sick It also shows symptoms. This shows that the civet cat does not meet such a characteristic of the natural host of the SARS virus. (Civet) is more of just playing the role of an intermediate host, and the true root cause is something else.
So where did these deadly viruses originate? Who is its natural host? Some experts put forward a bold idea.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: Which animal should I look for if I look for the next animal? Some experts have suggested that we should look for bats.
For virus researchers, bats have a special status. Among mammals, it is the second largest group after rodents. Its species account for 20% of mammal species, and it is widely distributed throughout the world. Bats are also natural hosts for many viruses, including Ebola virus, Marburg virus, rabies virus, Hendra virus, and Nipah virus. Due to the bat's special immune system, it is rare for it to carry the virus. In the long evolutionary process, bats have become natural hosts for hundreds of viruses.
In the 1990s, there were two serious zoonotic virus infectious diseases, which broke out in Australia and Southeast Asia, respectively. The root cause came from the same animal-bats. This raises the possibility for the research team to track the source of SARS virus, and whether the source of SARS is also bats.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: The first sample was taken from Guangxi. At that time, our experts were advised that the work they did was another virus. We called Nipah and Hendra, a virus that was also transmitted by bats. At that time, the virus was mainly found in fruit bats, so We basically picked fruit bats. After we took the samples back, we did a genetic test. After 8 months of testing, nothing was found.
Stumbled across the team's hopes
Eight months of hard work has yielded nothing. After all, there are more than 1,300 bats in the world, and more than 130 in China alone. Fruit bats, are there other bats? How to find it? It's a haystack.
At that time, the entire team was very frustrated, and Shi Zhengli was almost giving up, but just at this juncture, an accidental discovery made them hope again.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: The neighbor ’s research group was doing SARS virus detection in the early stage. They have some kits that can detect antibodies to SARS virus. We also took sera from bats at the time and found that there were Several (bat) species do have antibodies to SARS virus in their sera.
By detecting 408 bats from different families and monitoring antibodies and nucleic acids, the targets became clearer. Finally, a coronavirus similar to the SARS virus was found in bats. Daisy-headed bats are named for their complex horseshoe-shaped nasal leaves and are important hosts for many animal-derived viruses such as rabies. The discovery was published in the scientific journal of the international authoritative academic journal of the year, which aroused many concerns. But soon, doubts came again.
Shi Zhengli, Wuhan Institute of Virology, Chinese Academy of Sciences: Many experts have questioned that you still detected similar to it (SARS virus), but did not find a direct source,
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: Although it is similar to SARS virus and belongs to a family, it has a large difference in many genes in the genome, such as the S gene.
The "S gene" is also called spike protein gene, which is responsible for the binding of the virus to the receptor. When the virus infects the cell, it must first bind to the receptor on the cell surface to invade the cell and cause the infection.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: It ’s like the relationship between the key and the lock. What key unlocks what lock? If the S genes are different, the virus may use different receptors. We cannot infect humans and civet cats like the SARS virus, so we have to keep looking.
Shi Zhengli, Researcher, Wuhan Institute of Virology, Chinese Academy of Sciences: Guizhou, Guangxi, Guangdong, Hubei, Hunan, Henan, Henan, running around, wherever there is a bat cave , we go
Because SARS is a highly pathogenic and potent virus, after 2005, as the epidemic went away, there were fewer domestic researchers. But Shi Zhengli and her team did not stop tracking the source of the virus. They went southwest, south, and middle of China to find bat virus samples across the country. The farthest people have been to Motu, Tibet, Xishuangbanna, Yunnan, old forests in deep mountains, and bat caves in the wilderness.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: where there are bats, one is not easy to find. Second, it has a relatively long road and a steep terrain. Sometimes there is no road.
Luo Dongsheng, Ph.D. student, Wuhan Institute of Virology, Chinese Academy of Sciences: when catching bats in Guangdong, the water was deep in the cave. When I went in, my shoes didn't take off, and the water was almost at the waist. Net, you can hit the net, there is a hole that needs to be pushed in, you have to go in one or two hundred meters.
Bats are mostly in dark, humid, inaccessible caves, walking through deep mountains and dense forests, and often encounter some unknown dangers.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: We still made sufficient preparations. We put on socks and tied the socks to our knees, but that did n’t work. We walked along the road, and we found that there was blood in the bathtub Only then did I know that the moth has entered the body.
Luo Dongsheng, Ph.D. student, Wuhan Institute of Virology, Chinese Academy of Sciences: the most thrilling trip I took was to slide down the top of a cave next to the Yarlung Zangbo River Grand Canyon. Below is the waterfall. What I thought at the time was that I would not swim. It's over in the water.
The bats appear day and night, and in the evening, researchers will enter the bat cave fully or capture the bats at the mouth of the cave. After returning, they will take a virus sample on the workbench temporarily set up in the wild. Despite wearing gloves, the risk of being bitten by a bat remains.
Cui Jie, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: You can bite your hand through gloves, just like a needle.
Can be bitten by bats before being vaccinated
Bats carry a variety of severe viruses, including rabies. For this reason, before each field sampling, the team members will be vaccinated against rabies in advance. Wherever they go, they insist on non-invasive sampling. Minimize damage to bats and habitats.
Yunnan Xiaoshan Cave finds "key" for SARS virus
The samples were taken back to the laboratory and stored in a freezer at minus 80 ? C. Until 2011, a SARS-like coronavirus S gene closer to the SARS virus was first detected in a bat cave in Yunnan. In 2013, the Laboratory of Wuhan Institute of Virology, Chinese Academy of Sciences, isolated the first live virus of bat SARS-like coronavirus from the sample, and a more similar S gene, allowing this virus to use the same receptor as SARS virus and to Infect human cells. It was named "WIV1" by the English abbreviation of Wuhan Virus Research Institute to highlight the important value of this discovery. The results were published in the November 2013 issue of Nature. The "key" was finally found. But the secret uncovered by this small cave is far more than researchers expected.
Significance of SARS virus traceability and disease control
The successful isolation of WIV1 has allowed global scientists to diverge and debate the origin of the SARS virus. The target of this multi-year hunt became clearer-the SARS coronavirus originated from the chrysanthemum.
After years of hard work, the source of SARS has finally been traced, but scientists have not stopped, because in the bat cave where the S gene was first discovered, there are still more secrets hidden.
According to Hu Ben, there was an information gap left in the entire evidence chain at that time.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: In fact, the question about the bat origin of SARS virus has been answered almost, but because it still has some genes that are different from SARS virus, so it is still alive. Some questions are exactly how the SARS virus appeared in this bat.
The sampling of this bat cave in Yunnan continued for another 5 years. From these samples, the research team isolated 3 live viruses in succession, and obtained the full-length genomic sequences of a total of 15 bat SARS-like coronaviruses. Surprisingly, the 15 strains contained all the genome components of the SARS virus.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: We found a gene library of SARS virus in this place, that is, the different genes that make up these parts of the SARS genome can be carried by these bats in this hole. Found on the genome.
Hu Ben imported the viral genome sequence found in the bat cave of Yunnan and the genome sequence of SARFS virus into the gene recombination analysis software. As a result, it was found that the genome sequences of several strains of viruses after recombination had caused atypical pneumonia. The gene sequence of SARS virus is highly consistent.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: The fuchsia line and the dark blue line represent the two bat SARS-like coronaviruses that we found here, so the section in front of the SARS virus genome It is highly similar to the fuchsia bat virus gene. In the middle, it appeared a cross, and it became highly homologous with the dark blue bat SARS-like virus. We further speculate that the SARS virus might have been formed by recombination between these bat-like SARS-like coronaviruses that year.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: All SARS-like coronaviruses and various types of SARS-like coronaviruses were found here. And there are some viruses inside, and some viruses have potential for cross-species infection.
By comparison, the highest similarity between SARS-like coronaviruses found in bat caves and their respective genes is above 97%, which is highly homologous. Genetically, this means that the most direct ancestor of the SARS virus came from these bat viruses.
Experts said that although no virus exactly the same as SARS virus was found, the discovery fully confirmed that SARS virus originated in bats and revealed its possible way of production-genetic recombination.
Strengthen prevention and control to reduce invasion of wild animals
After 13 years of virus tracing, the origin of the SARS virus was finally found. But researchers also warned that new SARS-like viruses could emerge in the future.
In addition to increasing vigilance, reducing the invasion of wild animals and their living environment, and preventing market transactions of wild animals, we can effectively prevent the spread of new infectious viruses.
Shi Zhengli told us that there is a risk of SARS-like virus outbreaks in the future, but the study of virus traceability has found a direction for the prevention of new infectious diseases.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, the Chinese Academy of Sciences: In fact, you don't need to panic. There are actually many pathogens that wild animals carry in nature, but the chance of infecting people is very, very small, and it will not come to actively infect people. We now often see a new infectious disease in one or two years. This is a result of human activities. We humans are going to invade wild animal territories, we are going to travel, we are going to develop, we are going to cultivate, and there are many such (human activities). ), Is actually an infection caused by our human activities.
Hu Ben, an assistant researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: Minimize exposure to these infectious animals and minimize the risk of this SARS-like outbreak.
In the eyes of researchers, staying away from wildlife and protecting their habitat is the best source of prevention and control. Virus traceability can also lay the foundation for downstream prevention, diagnosis, vaccine development, and other basic research.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: The results of the work you are doing can be used for disease prevention or for future agricultural prevention. This is also something we are very happy about.
It took 13 years of research to finally answer people's questions. However, researchers tell us that for this topic, they still have to answer many unsolved mysteries related to it, such as: How did the virus on Yunnan bats spread to animals and people in distant Guangdong? Why do bats carry so many powerful viruses without getting sick? Wait, the road ahead will be even longer.
Shi Zhengli, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences: What you see is a small step, actually we have obtained many, many smaller steps. In fact, doing this basic science is inherently lonely and you need to persist, you will always be a pioneer.
Almost everyone had a scientist dream when they were young, and they felt that scientists knew more, especially powerful. I do n’t know until I grow up. Why do scientists know so much? Because when everyone starts to forget, only they are persistently searching for the answer. Their greatest strength is not the instrument in their hands, but the spirit in their hearts. For the truth of science and the well-being of mankind, they are willing to endure any loneliness.
Scientists are the people who are advancing the world. They take truth as their mission and use curiosity and the spirit of exploration to continuously expand the upper limit of human cognition. Every discovery is a new beginning, and every answer will lead to new questions . Rather than trace the source of SARS, it is better to say that it has just begun, and scientists have traveled a long way and have never stopped. For their persistence and determination, we sincerely offer our most sincere respect!
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