Sun Yat-sen University's Shu Yuelong and other teams discovered for the first time that MX1 mutations increase human susceptibility to zoonotic H7N9 influenza viruses

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iNature avian influenza virus H7N9 rarely infects humans, but once it occurs, the mortality rate exceeds 30%, far exceeding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
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Exposure to poultry is the main risk factor for human productive H7N9 infection, but occupational poultry workers account for only 7% of all cases, indicating that genetic factors may play a role in virus susceptibility
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The continued transmission of these IAVs between humans has not been observed, which indicates the role of host genes
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On August 20, 2021, Shu Yuelong of Sun Yat-sen University and Martin Schwemmle of University of Freiburg, Germany, jointly published a research paper entitled "Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus" in Science Online, which uses whole-genome sequencing Comparing avian IAV H7N9 patients with healthy controls, it was observed that there is a strong association between H7N9 infection and the rare heterozygous single nucleotide variation in the MX1 gene
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MX1 encodes myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase, which is known to control IAV infection in transgenic mice
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 Most MxA variants have lost the ability to inhibit avian IAV in the transfected human cell line, including H7N9
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Almost all inactive MxA variants have a dominant negative effect on the antiviral function of wild-type MxA, indicating that there is an invalid MxA phenotype in heterozygous carriers
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This study provides genetic evidence for the key role of MX1-based antiviral defense in controlling human zoonotic IAV infection
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The Avian Influenza Virus (IAV) regularly crosses the species barrier and infects humans
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Although such spills are rare, they may represent the source of new pandemic virus strains
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One of the major poultry IAV zoonotic diseases in recent decades is caused by the H7N9 subtype
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In the spring of 2013, the first fatal case was reported in the Yangtze River Delta of China
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As of the end of 2020, a total of 1,568 confirmed laboratory cases have been reported, with a case fatality rate of approximately 39%
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The zoonotic H7N9 virus has acquired several characteristics necessary to adapt to a mammalian host, including altered hemagglutinin (HA) receptor specificity and enhanced viral polymerase activity
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Despite this, the molecular mechanisms that achieve cross-species transmission of avian IAVs are still not fully understood
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Exposure to poultry is the main risk factor for human productive H7N9 infection, but occupational poultry workers account for only 7% of all cases, indicating that genetic factors may play a role in virus susceptibility
.

The study used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare heterozygous single-nucleotide variants in the MX1 gene
.

MX1 encodes myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase, which is known to control IAV infection in transgenic mice
.

 Most MxA variants lose the ability to inhibit avian IAV in the transfected human cell line, including H7N9
.

Almost all inactive MxA variants have a dominant negative effect on the antiviral function of wild-type MxA, indicating that there is an invalid MxA phenotype in heterozygous carriers
.

This study provides genetic evidence for the key role of MX1-based antiviral defense in controlling human zoonotic IAV infection
.

Reference message: https://science.
sciencemag.
org/content/373/6557/918