Find out the path of neurotropic pathogen invasion to help prevent and control the source of zoonotic diseases
Pay attention to national key R&D plans
◎Our reporter Ma Aiping
The key special project of “Prevention and Control of Livestock and Poultry Major Diseases and Comprehensive Technology Research and Development of Efficient and Safe Breeding” ④
The project uses neurotropic viruses such as rabies virus and Japanese encephalitis virus as models to explore their pathogenic and immune mechanisms in depth. It can not only design and source drugs for rabies, Japanese encephalitis and other neurotropic zoonotic diseases Prevention and control provide a scientific basis, and can provide an important reference for the research of other neurotropic zoonoses.
Cao Shengbo Professor of Huazhong Agricultural University
The central nervous system is the “command center” of human and animal organisms, and it is also the last line of defense of the organism. Once lost, the resistance system will collapse across the board, and life may come to an abrupt end. In life, some pathogenic microorganisms have “special hobbies” that target the invasion of the central nervous system, which we call neurotropic pathogens. There are many kinds of pathogens of this kind, which are harmful to human and animal health.
According to statistics, in recent years, about 50% of new virulent infectious diseases can cause encephalitis or severe neurological symptoms in humans and animals, and nearly 80% of them are zoonotic infectious diseases. With changes in environment, climate and other factors, the types of neurotropic pathogens that can cause neuropathic symptoms are increasing day by day, and the situation for the prevention and control of neurotropic pathogens is more severe.
On June 20, a reporter from the Science and Technology Daily learned from the China Rural Technology Development Center of the Ministry of Science and Technology that the key special project of the national key research and development plan “the research and development of comprehensive technologies for the prevention and control of major livestock and poultry diseases and efficient and safe breeding” “Important neurotropic zoonoses” Significant results and breakthroughs have been made in the study of immune and pathogenic mechanisms, and major breakthroughs have been made in the discovery of rabies virus invasion receptors, Japanese encephalitis virus and Zika virus and other mosquito-borne diseases transmission mechanisms.
“Important Neurotropic Zoonotic Disease Immunity and Pathogenic Mechanism Research” project leader, Huazhong Agricultural University professor Cao Shengbo told the reporter of Science and Technology Daily that the project uses neurotropic viruses such as rabies virus and Japanese encephalitis virus as models to go deep. Exploring its pathogenic and immune mechanisms can not only provide scientific basis for the drug design and source prevention and control of neurotropic zoonoses such as rabies and Japanese encephalitis, but also provide scientific evidence for other neurotropic zoonoses. Research provides important reference.
Focus on exploring the mechanism of pathogen-host interaction
Project researcher and Professor Zhao Ling of Huazhong Agricultural University explained that neurotropic pathogens infect many hosts, and the interaction mechanism with the host is complex, and they also have the obvious characteristics of targeting the nervous system. Its immune and pathogenic mechanisms are difficult points that need to be broken through in research. .
“For example, rabies virus targets neuronal cells, and its mechanism of infecting neuronal cells and inducing nerve damage is still unclear. Therefore, finding the key receptors for virus invading neurons and analyzing the key switch for virus-induced nerve damage is the project. The difficulty of research is also the key to breaking through the problem of rabies treatment.” Zhao Ling said.
To this end, the Zhao Ling team found a lncRNA EDAL molecule related to rabies infection and found that it has a unique function of inhibiting the replication of rabies virus in the brain, thus revealing that lncRNA EDAL is a key molecule that inhibits the replication of rabies virus in the brain.
According to Shuai Lei, an associate researcher at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, as a project participant, the Harbin Veterinary Research Institute has discovered metabotropic glutamate receptor 2 (mGluR2) in the process of rabies virus invasion according to the host genome-wide RNA interference strategy. It plays an important role and proves that it is a new receptor for rabies virus to invade the central nervous system.
“The above two studies have found key receptors for rabies virus and important targets for inhibiting rabies virus in the brain, laying the foundation for the research and development of drugs for rabies treatment, and also bringing hope for the treatment of the disease.” Zhao Ling said.
In addition, the backbone of the project and the researcher of Tsinghua University School of Medicine Cheng Gong’s group revealed that the NS1 protein of Zika virus has the function of assisting virus infecting mosquitoes, and pointed out that the mutation of the virus site caused the Asian strain of Zika virus to infect Egypt. The enhanced ability of Aedes mosquitoes provides a scientific basis for explaining the outbreak of Zika virus in recent years, and it also opens up a new way of thinking for the development of new mosquito-borne virus blocking vaccines. Related research results have been published in authoritative journals such as Nature.
Reveal the epidemiological characteristics of rabies virus and Japanese encephalitis virus in my country
According to Cao Shengbo, the project mainly focuses on the pathogen ecology and transmission mechanism of typical neurotropic pathogens such as rabies virus and Japanese encephalitis virus, infection and replication mechanism, interaction mechanism with the host immune system, invasion of the nervous system and induction of nerve damage The molecular mechanism and other four stages of research are carried out.
With regard to Japanese encephalitis virus-induced neuroinflammation, Ye Jing, a professor at Huazhong Agricultural University, discovered that the virus infection can cause significant changes in the phosphorylation level of a series of host proteins, and revealed that the JNK1 protein plays an important role in the neuroinflammation caused by the virus. Therefore, the use of JNK inhibitors can effectively alleviate the neuroinflammatory response caused by the Japanese encephalitis virus and reduce the mortality of animals. This is an in-depth analysis of the pathogenic mechanism of the Japanese encephalitis virus, the discovery of new targets for the treatment of Japanese encephalitis, and the establishment of A new method for the treatment of viral encephalitis based on inhibiting the inflammatory response of the central nervous system provides an important scientific basis.
At the same time, the project carried out research on the pathogenic ecology and molecular epidemiology of rabies virus and Japanese encephalitis virus, and revealed the epidemic characteristics of rabies virus and Japanese encephalitis virus in my country, and helped scientific prevention of rabies and Japanese encephalitis. control.
“The project found that my country’s rabies virus has a new trend of spreading from wild animals to dogs and to humans. Among them, foxes have become the second largest source of infection of rabies in our country. Through molecular epidemiological analysis, the project proposed the prevention and control of rabies in my country. Strategy, that is, the same health strategy, means that human health and animal health are closely related and inseparable.” said Feng Ye, an associate researcher at the Institute of Military Veterinary Medicine, Academy of Military Medical Sciences.
In addition, in terms of Japanese encephalitis, the project revealed the trend of spreading to the west and north in the prevalent areas of Japanese encephalitis in my country, and the changing characteristics of the dominant genotype from genotype III to type I.
In the summer of 2018, there was an outbreak of Japanese encephalitis in Ningxia, Gansu and other places in my country. The team of researcher Wang Huanyu of the Chinese Center for Disease Control and Prevention of the project participating unit quickly determined the pathogen of the epidemic, the local dominant mosquito species, the positive rate of the virus in the mosquito and its genotype, and quickly carried out emergency immunization of the population in the epidemic area.
“The project team of Chinese medicine and veterinarians cooperated closely to carry out mosquito elimination, technical training and animal immunization, etc., and timely handled and effectively prevented the Japanese encephalitis epidemic in Ningxia and other places.” Wang Huanyu said.
The pathogenic mechanism of rabies is the main direction of the future
“The project has achieved a series of breakthroughs, and the following aspects have played an important role.” Cao Shengbo said. First of all, the project team gathered 38 units from 14 units engaged in the research of neurotropic viruses such as rabies virus and Japanese encephalitis virus. Research backbone.
Secondly, the collaboration between veterinarians and human-medicine is an important organization method for carrying out research and prevention and control of zoonotic diseases. 60% of human infectious diseases are zoonotic, and 75% of new human infectious diseases originate from animals. Therefore, under the new concept of One Health, the research, prevention and control of zoonotic diseases urgently requires close cooperation between veterinarians and human doctors.
Third, interdisciplinary integration is an important way to solve scientific problems. The subject background of the project members covers multiple subject areas such as virology, neurobiology, immunology, etc., and can achieve complementary advantages, collaborative innovation, and finally work together to solve important scientific problems in the field.
“The China Rural Technology Development Center of the Ministry of Science and Technology of the project management unit plays an important guiding role in the organization, implementation and management of the project. For example, the proposed “full chain design, integrated implementation” management model, and the “performance four questions” evaluation system Etc. have effectively promoted the smooth implementation of the project and the condensing of the iconic results of the project, and enabled the research results of the project to produce better social and economic benefits.” Cao Shengbo pointed out.
Although this project has achieved many important research results, there are still many unresolved scientific problems in the research field of neurotropic zoonoses.
Rabies is an ancient zoonotic disease. The mortality rate after the onset is almost 100%. There is still no effective treatment method. “Although the important progress of this project has brought hope to the treatment of rabies, there is still a long way to go to completely solve the world problem of rabies treatment. Therefore, in-depth exploration of the pathogenic mechanism of rabies will be the main direction of the project team in the future. Later, the project team We will look for breakthroughs in metabolism and nerve damage repair, and repair the nerve damage while clearing the rabies virus in the central nervous system, in order to find a clinical treatment method for rabies.” Cao Shengbo said.
In addition, the epidemiological study of the project team showed that the distribution characteristics, genetic evolution, and transformation of dominant genotypes of Japanese encephalitis virus and rabies virus in the host are changing, and these zoonotic diseases are being tracked continuously. The spreading law of the epidemic is of great significance to the prevention and control of the source of the epidemic.
“In short, neurotropic zoonoses have a wide variety and great harm, and the prevention and control situation is still severe. We need to focus on this country’s major needs and important areas, and continue to conduct in-depth research on new scientific issues to protect this type of disease. Prevention and control provide scientific and technological support.” Cao Shengbo said.
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