Science: Sun Yat-sen University's Shu Yuelong team solved the mystery of H7N9 avian influenza infection

Influenza virus species, a wide host range, widely distributed in wild birds, waterfowl and land birds and other natural hosts, in recent years, more and more bird flu virus spread across a host infected humans, serious harm to human health, and to global public Health and safety pose major challenges.
At present, the avian influenza viruses that can infect humans mainly include H5N1, H5N6, H7N9, and H9N2
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The continuous cross-species transmission of these viruses reminds us that the threat of another influenza pandemic always exists, and the World Health Organization has always regarded the influenza pandemic as one of the top ten public health threats facing mankind

Avian influenza infection

In the spring of 2013, the team of Professor Shu Yuelong of Sun Yat-sen University reported for the first time in the world that a new type of low pathogenic avian influenza A (H7N9) virus (LPAI H7N9) can cause human infection and death (NEJM 2013).
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The H7N9 avian influenza virus has caused five waves of epidemics in the population, resulting in the infection of 1,537 people in the mainland of China, including 612 deaths, with a case fatality rate of about 39.

Then, under the same exposure conditions, why only a few people will be infected with the H7N9 avian influenza virus, while most people are not infected, is still an unsolved mystery
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In order to overcome this problem, Professor Shu Yuelong's team speculated that host genetic factors may have played an important role
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In order to prove this hypothesis, the team adopted a case-control study method and included a total of 217 confirmed cases of H7N9 avian influenza (real time RT-PCR test positive) and 116 occupational exposure controls (real time RT-PCR) that are epidemiologically related to the confirmed cases.

The research was titled: Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus, and was published online on August 20, 2021 in the journal Science
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Myxovirus resistant (Mx) gene is one of the first interferon-induced antiviral genes discovered.
The human MX1 gene can encode human myxovirus resistance protein A (Human myxovirus resistance protein A, MxA), which is a dynamic protein.
GTPase, a class of macromolecules in the superfamily, has antiviral effects on a variety of RNA viruses and DNA viruses, including influenza A viruses and hepatitis B viruses
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Further research results showed that a total of 17 rare MX1 mutations were found in H7N9 avian influenza cases, including 15 missense mutations, 1 nonsense mutation and 1 splice site mutation
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In vitro experimental verification shows that 14 of these mutations will affect protein function

After a first-generation sequencing verification, the rare MX1 mutations carried by H7N9 cases are all heterozygous mutations, so does wild-type MxA continue to exert its antiviral effect in the body?

The research team further carried out a study on the dominant negative effect of MxA mutants on wild-type MxA, and the results showed that 12 MxA mutants that lost antiviral activity had a dominant negative effect on wild-type MxA, indicating that MX1 heterozygotes were not protected
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This study found for the first time the MX1 gene mutation that is associated with the increased risk of human infection with the H7N9 avian influenza virus.

The results of the study explained for the first time why only a small number of people would be infected with the H7N9 avian influenza virus under the same exposure conditions.
At the same time, these mutations are rare mutations, and the mutation frequency in the population is less than 0.
5%, which indirectly indicates H7N9.
The current risk of avian influenza virus causing an influenza pandemic is low; the research results also provide a scientific basis for possible future surveillance of high-risk populations, and further promote the precise prevention and control of infectious diseases
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Precise

Schematic diagram of rare variants of MX1 found in H7N9 avian influenza cases

Schematic diagram of the rare variants of MX1 found in H7N9 avian influenza cases

Dr.
Chen Yongkun, School of Public Health, Sun Yat-sen University (Shenzhen), Laura Graf, a postdoctoral fellow at the University of Freiburg, Germany, Liao Qijun, a doctoral student in the School of Public Health, Sun Yat-sen University (Shenzhen), and Chen Tao, Associate Researcher from the Institute of Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, are the joint firsts of the paper The authors, Professor Shu Yuelong from the School of Public Health, Sun Yat-sen University (Shenzhen), Professor Martin Schwemmle from the University of Freiburg, Germany, and Researcher Wang Dayan from the Institute of Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention are the co-corresponding authors
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This research is supported by the National Key R&D Program and Shenzhen Science and Technology Program

prevention

Original source:

Original source:

Yongkun Chen, et al.

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