Virus “self-cultivation”

Although the virus is hateful, from its point of view, its living environment is also very dangerous. If you don’t pay attention, it is easy to be attacked by the host’s immune system and even “killed.” Therefore, their main way of survival is mutation, and fickleness is also the most difficult part of the virus to deal with. There are two main ways of virus mutation: one is genetic recombination, that is, different viruses “marry” to form a new virus; the other is genetic mutation to achieve self-upgrading. The purpose of these two kinds of mutations is to continuously improve themselves, in order to achieve the “continuation” of the virus family.

Gene recombination produces new virus

There are many types of viruses, and the genomes of viruses of different species vary greatly. Even if there are 90% similarities between different subtypes of viruses of the same species, there may be many significant differences in genetics, and these genetic differences often determine the characteristics of the virus. When viruses of different subtypes occasionally infect the same host, genetic recombination or rearrangement occurs between these genetically similar viruses. In other words, two or more unique sequences from different subtypes of viruses may be integrated into the same virus to form a “hybrid” virus, and suddenly have some new special abilities.

Gene recombination is a natural phenomenon in the process of gene replication. Infecting the same host cell with viruses of different subtypes, it is necessary to use the host’s nucleic acid replication system and protein synthesis system to synthesize new virus particles. In synthetic virus particles, gene fragments of viruses of different subtypes may be mixed together to recombine new viruses. Most of the time, this mismatch is not a good thing for the virus, and it may even be fatal. But sometimes it may produce a new virus with a certain special ability, such as the ability to cross species boundaries, that is, it can only infect a certain kind of animal, and after genetic recombination, it can infect another animal, even humans. Of course, gene recombination between viruses can also produce the same effects as gene mutations, such as enhancing virulence and infectivity, increasing the types of cells that can be infected, evading host immune system attack, enhancing antiviral resistance, etc., and even helping viruses Reverse the adverse effects of genetic mutations.

Virus recombination process

In nature, almost every virus undergoes different degrees of genetic recombination during evolution. AIDS has caused more than 32 million deaths worldwide, and the human immunodeficiency virus (HIV) that causes AIDS is a retrovirus whose evolution mainly relies on gene recombination, and its gene recombination rate is even higher than the gene mutation rate. There is definite evidence that the HIV virus that infects humans is evolved from the simian immunodeficiency virus that originally only infects non-primates through recombination and mutation. The earliest recombination may be the apes of African green monkeys and black-brow monkeys. Occurs between immunodeficiency viruses. In 2009, the influenza A virus (H1N1pdm09), which first broke out in the United States, infected more than 60 million people worldwide and killed about 18,500 people. Genetic analysis shows that the H1N1pdm09 influenza virus is a recombination of a swine influenza virus circulating in North America and a swine influenza virus circulating in Eurasia. The former contributes 6 gene segments and the latter is 2 There are at least four gene segments, and at least 4 gene segments are formed by multiple gene recombination from human, avian and swine influenza viruses.

Mutations promote virus upgrade

Gene mutation is the basic way of species evolution, and viral gene mutation is no exception. Gene mutation generally refers to the change of a single base or a few bases during DNA or RNA replication. For organisms or viruses, genetic mutations are also disadvantageous in most cases, even fatal, and only in rare cases are they beneficial.

Different viruses have different gene mutation rates. In general, the mutation rate of RNA viruses is much higher than that of DNA viruses. For example, the average mutation rate of a base in DNA viruses per generation is one in 100 million to one million, while the mutation rate of RNA viruses is one in million. To one in 10,000, retroviruses are the highest. For example, the average mutation rate of human immunodeficiency virus (HIV) is about one in 30,000. In contrast, the average mutation rate of human cell DNA is comparable to the lowest mutation rate of DNA viruses.

If the virus does not cause much harm to the host, then the host immune system will not put too much pressure on the virus. At this time, the genome mutations of different generations of viruses are usually not too large, and the virus and the host will be fine. For example, the relationship between bats and viruses is relatively “harmonious.” Bats are a super virus library in nature and can be infected with hundreds of viruses, such as coronavirus, Ebola, rabies, and other deadly human viruses, but bats are safe and sound. If the host cell immune system is relatively powerful, or if it is assisted by some antiviral drugs or vaccines, the virus will face greater pressure to survive. At this time, viruses with special genetic mutations may show competitive advantages under similar pressures, such as Demonstrate resistance to drugs and vaccines, evade host immune system attacks, enhance the ability to infect host cells, adapt to new tissues and organs, and even new hosts, so as to survive in new environments or new pressures Opportunity to go down.

Frequent gene mutations are observed in many viruses such as HIV, influenza, hepatitis B and C viruses, and these gene mutations also bring great challenges to vaccine development. Sometimes a point mutation of a viral base may defeat a vaccine that humans have developed over several years. Influenza vaccines are usually produced from chicken embryos. The approximate process is to inoculate pathogenic influenza viruses into aseptically cultured chicken embryos, and then collect the influenza viruses that proliferate in large quantities in the chicken embryos for inactivation treatment to prepare an inactivated or Attenuated vaccine. The protection rate of general influenza vaccines is lower than 50% to 70%, while the protection rate of influenza vaccines against H3N2 strain is only 33%. Researchers at the Scripps Research Institute in the United States carefully analyzed the genome sequence of the H3N2 strain that was passaged in chicken embryos and found that the 194th amino acid on the hemagglutinin glycoprotein of the strain was changed from leucine to proline acid. It is precisely because of this mutation that the H3N2 strain is adapted to grow rapidly in chicken embryos, which ultimately leads to a very low protection rate of influenza vaccines produced by this strain.

Of course, virus mutations are not entirely beneficial to the virus itself. Researchers from the University of Missouri School of Medicine and Japan’s National Center for Health and Medical Research discovered a point mutation in the HIV virus in an AIDS patient, which actually reduced the virus’ resistance to anti-HIV drugs.

This reminds scientists that the genetic mutations of deadly viruses should be monitored in time, because by studying these mutations, we can accurately identify the causes of drug failure, immune failure, and outbreaks, and help find effective ways to fight the virus.

Coronavirus mutation needs to be ascertained

As a coronavirus that has frequently appeared in the past ten years, the evolution of its virus family is naturally inseparable from gene recombination and mutation, especially the acute severe atypical pneumonia (SARS) coronavirus in 2003 and the Middle East respiratory syndrome in 2012 (MERS) Coronavirus and the new coronavirus (COVID-19) mutation that appeared in December 2019 are the most noticeable.

Identifying the source of the virus is essential for controlling the epidemic and preventing new outbreaks. Starting with the mutation of the coronavirus is an effective means to identify the source of the virus. Since the epidemic began in November 2002, after more than ten years of hard work, scientists finally clarified that the ultimate natural host of SARS coronavirus is bats, and the first confirmed civet cat is the intermediate host. In 2017, Shi Zhengli led a team from the Wuhan Institute of Virology, Chinese Academy of Sciences, and found all the genetic elements of the SARS virus in a bat in a cave near Kunming, Yunnan Province. Therefore, scientists speculate that human SARS coronavirus may be formed by a series of genetic recombination of bat SARS coronavirus and civet SARS-related coronavirus in this cave or elsewhere.

The natural host of the MERS coronavirus is also a bat, and the intermediate host is a camel. Scientists speculate that the MERS coronavirus is more prone to genetic recombination. Scientists have observed that the spike protein gene of MERS coronavirus and another gene are inconsistent with other genome locations. It is speculated that some MERS-related coronaviruses have undergone multiple genetic recombination between bats, camels, or between bats and camels, and finally formed MERS coronavirus that can infect humans.

As the seventh coronavirus that can infect humans, the new coronavirus (COVID-19) is more contagious than their “predecessors”. On February 3, 2020, Shi Zhengli’s team from Wuhan Institute of Virology, Chinese Academy of Sciences and Zhang Yongzhen’s team from Fudan University simultaneously published a research paper online in the journal Nature, confirming that bats may also be the natural host of the new coronavirus. At the same time, multiple research teams at home and abroad, including South China Agricultural University, Baylor College of Medicine, and the University of Hong Kong, respectively found that the pangolin coronavirus genome is more than 90% similar to the new coronavirus, and they believe that pangolin may be one of the intermediate hosts of the new coronavirus. Preliminary research results indicate that the new coronavirus may be produced by the recombination of bat coronavirus and pangolin coronavirus, but this conclusion requires more and more direct evidence.

Fortunately, however, scientists have not observed significant mutations in the new coronavirus. If the epidemic is controlled before the new crown virus mutates on a large scale, then we can quickly defeat the virus. Otherwise, it may cause a pandemic.