Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.

Five outbreak waves have occurred since the low-pathogenic avian influenza A(H7N9) virus (LPAI H7N9) first emerged in spring 2013 in eastern China [1]. Highly pathogenic avian influenza A(H7N9) (HPAI H7N9) viruses, derived from their LPAI H7N9 counterparts, have recently been isolated from humans and resulted in fatal outcome in Guangdong, China (A/Guangdong/17SF003/2016 (SF003) and A/Guangdong/17SF006/2017 (SF006)) [2]. Both viruses contain an insertion of four amino acids (KRTA) in the haemagglutinin (HA) proteolytic cleavage site, indicating their pathotype switch from LPAI to HPAI. Furthermore, they retain a series of genetic features contributing to the ability to infect humans (e.g. 186V in the HA protein (H3 numbering) and 627K in the PB2 protein) that raise concerns regarding their pandemic potential. Amino acid substitutions associated with resistance to neuraminidase inhibitors (NAIs) have been detected in both SF003 and SF006 viruses. Therefore, to update public health risk assessment, we investigated trypsin-dependent infectivity, receptor binding properties, antigenic alternations of the HPAI H7N9 viruses, as well as their sensitivity to antiviral drugs. All LPAI H7N9 viruses in this study were isolated from humans.