The new coronavirus is spreading around the world. Everyone wants to know, where does this virus come from? The job of finding the source of a disease-causing virus is called “virus tracing.”

“This is not just to satisfy curiosity, but more importantly, it is of great significance to the prevention and treatment of infectious diseases. Finding the source of the virus and understanding how the pathogen develops into A human-causing virus can only answer the question of whether the virus will recur, that is, whether everyone is concerned about whether it will make a comeback.

However, despite the painstaking exploration of scientists around the world, it seems that the origin of the new coronavirus is still confusing. “In fact, not only the new coronavirus, but many diseases in human history, such as AIDS, SARS, etc., although great progress has been made in the exploration of its source, the tracing of the virus itself is a scientific problem and very complicated. It takes a long time and there is uncertainty. “Zhao Guoping said.


Source tracing based on scientific evidence to find pathogens must meet Koch ’s law

“For tracing of unknown pathogen viruses, there are at least two steps: the first step Find the pathogen that causes the disease first; the second step is to determine which animal was the first to be infected (or the natural carrier), that is, the natural host of the virus. At this step, you also need to explore the virus from the natural host to the infected person. Then the process and mechanism of interpersonal communication. “Zhao Guoping said.

Zhao Guoping said that virus tracing requires evidence, which is the process of scientific proof. There are two main types of evidence, one type is biological evidence, including etiology, clinical medicine, and epidemiology. Its advantage is “real world” imaging, but there may be human interference during the acquisition process. , And the difficulty of the experimental process; the other type is molecular biological evidence, including genome sequencing, antibody detection, etc. Its advantage is “exact”, but it is not so easy to establish contact with biological evidence.

To find pathogens, Koch ’s Law needs to be met. Wu Guizhen, a researcher at the Institute for Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, introduced that Koch ’s rule was proposed by German bacteriologist Robert Koch. It refers to the determination of a virus as a pathogenic microorganism that requires four criteria: in each case The same microorganisms are present in the human body and do not exist in healthy people; such microorganisms should be isolated from the host and cultured purely in the culture medium;For a healthy and sensitive host, the same disease will occur repeatedly; this microorganism can be isolated and cultured again from the host with experimental disease.

When the SARS outbreak occurred, two teams at Erasmus University Rotterdam in the Netherlands used this rule to determine that SARS-CoV was the cause of SARS. They used SARS-CoV to infect crab-eating macaque monkeys, and showed symptoms similar to human infection with SARS-CoV. The virus isolated from the infected monkey was the same as the virus at the time of the initial vaccination. Specific seroconversion.

However, Wu Guizhen said that finding the pathogen is only the first step in tracing the source. Whether the Chinese chrysanthemum bat is the only natural host of SARS, and how the virus it carries mutates into the virus carried by the raccoon dog needs further study.

“It takes a long time to search for pathogens in full accordance with Koch ’s law. In today ’s era, molecular biology methods such as serum transformation and gene sequencing are required to speed up the identification of suspected pathogens. Identify the true body: what kind of species it belongs to, whether it is a new species that has not been recognized, etc. From the whole process of traceability, the information evidence obtained by the two major technologies of biology and molecular biology will eventually converge into a chain and prove each other , It is considered to have truly completed the task. “Zhao Guoping added.


“Patient No. 0” is the key to tracing and it is difficult.

“Generally speaking, there are two paths for virus tracing, one is epidemiology The investigation, the second is the investigation of the virus distribution in animals and the environment. “Said Zhao Wei, director of the Biosafety Level 3 Laboratory of Southern Medical University.

Zhao Wei said that the epidemiological survey of the traceability of general infectious diseases starts from the contact history of the first discovered patient, that is, to find the “patient zero” , But this job search can be even more difficult.

Taking AIDS as an example, from October 1980 to May 1981, five previously healthy young people in Los Angeles developed Pneumocystis carinii Pneumonia, a very rare and serious infection, usually only appears in people with severely weakened immune systems. The condition of five young people deteriorated rapidly, and two people had died when reported. This is the earliest AIDS patient discovered, but at that time it was speculated that this disease has spread in the world for a long time.

8 years later is the first in 1988The study found an earlier American patient. When the researchers tested a tissue sample left by a 15-year-old named Robert Rayford in 1968, they found HIV positive. After another 10 years, in 1998, scientists found a blood sample from 1959 in Kinshasa, Congo, and found that it contained HIV-1. This is the earliest AIDS “patient zero” that can be traced back to now. But is he really the “zero” number?

Secondly, the investigation of virus distribution in animals and the environment is the most direct and important method. Zhao Wei said that if scientists discovered that primates in southern Cameroon in Africa had a virus similar to HIV, SIV, that is, monkey immunodeficiency virus. Therefore, some scientists put forward the theory of “injured hunter”, that is, an injured hunter who was exposed to the virus in the primate was the first to be infected. Ebola hemorrhagic fever, one of the most dangerous infectious diseases in modern times, is currently believed by most scientists to be derived from fruit bats, because there are different types of fruit bats that can carry this virus throughout central Sahara and southern Africa.

In recent years, bioinformatics technology has advanced rapidly. Scientists can determine the genetic relationship and transmission process between different virus strains through gene homology comparison, and even through ” “Molecular Clock Theory” extrapolates the origin time of a virus. But in terms of traceability, these cannot replace traditional epidemiological investigations.

In Zhao Guoping ’s view, the traceability of new viruses of natural origin is like a criminal police case. When the criminal police arrived at the crime scene, they first collected evidence, and then conducted various investigations to form various hypotheses; shun vines, rule out and find new evidence and new clues, and finally find the suspect. At the same time, the suspect confessed the criminal process, and identified the first scene of the crime and the hiding place of the crime tool, and confirmed each other with the evidence obtained. Problems in any of these links may have no results.


It is difficult to trace the source and everyone should have reasonable expectations

Viruses are very cunning, especially the genes are made of ribonucleic acid (RNA) instead of deoxyribonucleic acid (DNA ) The formed virus is more prone to mutation, and the degree of mutation is higher and faster.

Zhao Guoping introduced that coronavirus is a more cunning RNA virus. The genome is relatively large (three times the HIV virus genome), and it is also prone to mutations including large fragments such as deletions and recombination; of course, most of the mutations are unfavorable for the growth and reproduction of the virusTherefore, it was naturally eliminated during the process of virus replication.

Zhao Guoping believes that in the process of cross-species transmission, the virus needs to accumulate those mutations that adapt to the new host (human) to form a “transmissive clone” that spreads among the population That is to say, it is now repeatedly tested and sequenced to spread the virus strains all over the world. However, most of the mutations in this early accumulation process have no obvious “phenotype” of human infection, and the probability of being found is naturally very low; but this is the “scientific evidence” required for traceability. .

Taking SARS as an example, Zhao Guoping explained that after its outbreak, scientists have been looking for the source. In 2005, scientists discovered SARS-like coronavirus in three bats, but the genome sequence was too different from the SARS coronavirus genome. Until 2015, the SARS-like coronavirus was found in Chinese chrysanthemum bats, with 96% similarity to the human SARS coronavirus genome sequence, and the S protein amino acid sequence similarity to the human cell receptor ACE2 reached 97%, Only to basically reveal the natural host of SARS coronavirus.

“Virus tracing is extremely difficult and contains many uncontrollable factors. Some evidence has been lost and may never be found. In many cases, it is not possible to connect the chain completely It is possible. Some of them may not be clarified by long-term research, but can only form inferences, and more still find nodal evidence. For this, everyone should have a reasonable expectation. “Zhao Guoping emphasized.

(Original title: Virus tracing is difficult and requires scientific proof)