According to recent research, rare, single-nucleotide variants in the MX1 gene increase the human susceptibility to zoonotic H7N9 avian influenza infection. The results of the study offer genetic evidence for a vital role of the MX1-based antiviral defense in controlling zoonotic influenza A virus (IAV) infections in humans.
Avian Influenza. Image Credit: Fahroni/Shutterstock.com
The results also show that people with such genetic vulnerabilities can act as incubators for the transmission of virulent novel IAV subtypes.
Even though zoonotic avian influenza infections are uncommon, spillover events persist as a concern as they can depict a source of novel pandemic virus strains. The most recent outbreak was triggered by the H7N9 avian influenza virus, first found in humans in 2013.
Although human infections of H7N9 remain relatively rare and constant transmission of the virus between humans has not yet been noted, this influenza subtype can be exceptionally deadly, with a mortality rate of around 39%, outpacing that of SARS-CoV-2.
In spite of their potential risks, the molecular mechanisms that facilitate cross-species transmissions of IAVs are not fully understood. At present, exposure to poultry is the major risk factor for human H7N9 infection. This being said, occupational poultry workers represent only 7% of all cases reported. These observations indicate that human genetic factors might have a role to play in zoonotic virus susceptibility.
Yongkun Chen and co-workers employed whole-genome sequencing to identify the role of rare gene mutations in H7N9 infection in 220 Han Chinese patients who had H7N9 infection from 2013 to 2017 and among a population of healthy poultry workers who can be greatly exposed to the virus, as controls.
In the case of workers with laboratory-confirmed H7N9 infections, Chen et al. found multiple defective single-nucleotide variants in the MX1 gene, which codes for an interferon-induced antiviral protein recognized to control IAV infections in mice. The researchers state that most of the recognized MX1 variants (14 out of 17) had lost the capability to inhibit avian IAV, including H7N9, in in vitro infection experiments in human cells.
The researchers add, “In the future to decrease the risk of pandemic viruses, it will be important for disease surveillance ... to screen vulnerable human populations for deleterious variations in MX1.”
Chen, Y., et al. (2021) Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus. Science. doi.org/10.1126/science.abg5953.