Should we worry about the mutation of the new coronavirus in Japan?
——Interview with Umi Kitasato, a virologist at Nagasaki University, Japan
International war "epidemic" operation
Chen Chao, our reporter in Japan
The latest research of the National Institute of Infectious Diseases in Japan found that the March epidemic in Japan was mainly caused by the new coronavirus with related gene sequences in Europe, but the epidemic has temporarily subsided in late May. Since mid-June, a large number of mutant viruses with new gene sequences have appeared with Tokyo as the center, and they have spread rapidly across Japan. Most of the patients infected after June are infected with this mutated new coronavirus.
Research shows that from a global perspective, from the end of 2019 to July this year, the new coronavirus genome has an average of about 15 base mutations randomly. What is the impact of virus mutation? With this question, a reporter from the Science and Technology Daily interviewed Dr. Kitasato, a virologist at Nagasaki University in Japan.
The pathogenicity of the mutant virus is weakened and the infectivity is enhanced
Kitasato told the Science and Technology Daily reporter that based on virus samples collected from 3,700 people infected with the new coronavirus in Japan, genome sequence analysis revealed that the mutation of the European virus genome has also been confirmed in Japan. After the emergency was lifted across Japan in early June, infections began to increase rapidly again, showing a second wave of epidemic trends, which are still expanding, and the virus has been found to have mutated. These variations are different from those of the European subtype in March.
Kitasato believes that although the impact of these mutations on the virus needs further research and verification, judging from the current situation, Japan's new coronavirus mutation does not need to be particularly worried. Because these mutated virus strains are mainly formed in the recessive transmission of asymptomatic or mild virus infections, that is to say, these mutated viruses have not caused the infected persons to become severely ill through continuous transmission, and also show the pathogenicity of these viruses. Weakening.
At the same time, the rapid spread of the epidemic in Japan after June shows that the infectivity of these mutant viruses has increased significantly, leading to rapid spread of the virus. Especially as the temperature gradually rises, the virus infection is still expanding. It can be speculated that these mutations may have an impact on the stability of virus particles under high temperature conditions, which means that these mutations may increase the stability of the virus and make it relatively stable. It can also maintain the ability to survive and infect for a period of time in high temperature environments.
Not only Japan, but the global trend of new coronavirus mutation
Kitasato said that, according to research reports in Japan, these mutations are different from the virus subtypes currently circulating in Europe and the United States, and are mutations that have emerged independently after the second wave of large-scale epidemics in Japan. Strangely, intermediate variants between these variants and the early European epidemic strains were not found. According to the virus gene sequence analysis of the database, it is closer to the virus strain isolated in Florida, USA. One possibility is a subtype that became popular in Japan after being imported from the United States. As for whether these mutations have appeared globally, there is no final conclusion, and more virus analysis is needed to confirm in the future.
In addition, according to recent research reports in the United States and China, the aspartic acid (D) at position 614 of the membrane surface spike protein (S protein) of the currently circulating new coronavirus strains has mutated into glycine (G), and the D614G mutation This leads to a change in the conformation of the virus S protein, because the mutation of D614G makes the S protein a new cut point of elastase-2. Elastase-2 is a protease widely distributed in the pancreas and white blood cells. If the virus S protein has this enzyme cutting point, the virus S protein will be cut into two fragments S1 and S2 in the blood by this enzyme, so that non-infectious virus particles can be activated into infectious virus particles, or Virus particles are more infectious. Because the new coronavirus is a protease-dependent virus, the infection is mainly determined by the S protein, and the S protein must be cleaved by protease into two subunits of S1 and S2 virus to be infectious. The S1 subunit is responsible for binding its cell receptor ACE2, and the S2 subunit has a membrane fusion function, responsible for the fusion of the viral envelope and the cytoplasmic membrane, so that the viral nucleic acid and protein are released in the cell.
It has been experimentally confirmed that this D614G mutation increases the virus's ability to infect cells by nearly 10 times. This mutation first appeared in Europe in March, and most of the new coronaviruses currently circulating in the world are this mutation. The National Institute of Infectious Diseases of Japan also confirmed that the virus strains currently circulating in Japan also include this mutation. As the infected population continues to expand, virus mutations tend to be more infectious but less pathogenic. This tendency has appeared all over the world.
Mutation may have a certain effect on the vaccine, but it will not make the vaccine completely ineffective
According to Kitori, among several vaccines currently developed in the world, the most important and leading one is the vaccine that uses adenovirus vectors to express the virus S protein developed by the Chinese and British teams. This vaccine can induce the production of neutralizing antibodies to S1, mainly targeting the receptor binding domain (RBD) at the binding site of S1 and its cell receptor ACE2, preventing the virus from binding to cell surface receptors and playing a role in preventing infection.
At present, these new mutations discovered in Japan cannot confirm whether it will affect the combination of virus S1 and ACE2. If its impact is great, it may have a certain impact on the vaccine, but it will not make the vaccine completely ineffective. The reason is that the vaccine expressed by the viral vector is equivalent to a live vaccine. It can not only induce the immune system to produce antibodies, but also induce cellular immunity to the virus. These cellular immune responses will eventually completely remove the infected virus from the body. In addition, there are many kinds of antibodies induced by the vaccine. In addition to the antibodies that bind to RBD, antibodies that bind to other positions of the virus S protein may also inhibit or affect the binding of the virus to the receptor and play a role in inhibiting virus infection.
The development of vaccines is to compete with the virus
Kita-ri told the Science and Technology Daily that the gene mutation of the RNA virus is very cunning. The continuous spread of RNA viruses in the population is the process of fighting against different human immune systems. The virus will continue to mutate and evolve to produce variants that can evade recognition and attack by the immune system, and ultimately successfully defeat the immune system. . The surviving virus will form a dominant group and continue to spread among the population. And these viruses that can survive and continue to spread have the ability to resist different human immunity. Therefore, as long as the virus continues to spread in the population, it will cause the virus to continue to accumulate new mutations. By effectively suppressing the spread of the virus as early as possible, the emergence of new mutant viruses can be suppressed, which can also buy precious time for vaccine development. The development of vaccines is a race against the virus for time and speed.
Kitasato said that the various measures and efforts China has taken to fight the epidemic have proved to be effective and set a model for the world. Looking at the world, it is regrettable that the epidemic situation in the United States, Brazil, India and other countries is not well controlled. The global epidemic situation continues to spread and cannot be effectively controlled. The struggle between humans and the new crown virus may last for a long time, as short as two to three years, or a longer-term and protracted war needs to be planned. Although with the spread of the epidemic, it is not ruled out that new mutant viruses will appear in the future, leading to severe infections and increased deaths. However, Kitari still believes that as long as the whole world unites and gathers the power of human wisdom and technology, humanity will eventually defeat this virus.