Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus

Poultry passport to pandemic What conditions are required to nurture the seeds of a pandemic? The avian influenza virus H7N9 rarely spills over into humans, but when it does, mortality exceeds 30%, far in excess of that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chen et al . used whole-genome sequencing to investigate the contribution of rare mutations among poultry workers who can be exposed to high levels of H7N9. Multiple defective single-nucleotide variants in the myxovirus resistance Mx1 locus were prevalent in H7N9 patients. In vitro infection experiments and influenza polymerase activity assays showed that 14 of the 17 MxA protein variants had no antiviral activity. Thus, individuals with such genetic vulnerabilities, when exposed to high virus loads, may act as crucibles for transmission of virulent new influenza subtypes. —CA