Influenza A virus H7N9 is a negative sense RNA virus with two key surface glycoproteins, the haemagglutinin (HA) and the neuraminidase (NA). It is capable of undergoing both antigenic drift (driven by point mutations) and antigenic shift (as a result of co-infection and genome reassortment). The NA of H7N9 influenza viruses isolated from human cases most closely resembles that found in migrating birds from South Korea [
10]. In contrast, the HA of human H7N9 influenza viruses can be traced back to the HA of an H7N3 influenza virus from domestic ducks [
11]. Typically, the HA of avian influenza viruses shows a strong preference to bind to α-2,3 linked sialic acids whilst the HA of human influenza viruses typically binds to α-2,6 linked sialic acid [
12]. Since the upper respiratory tract of humans is rich in α-2,6 receptors, human influenza viruses are well adapted for efficient human-to-human transmission [
13]. However, via the introduction of point mutations in viral HA (Q226L/I, G186 V), the avian H7N9 influenza virus increased its avidity to human receptors [
13]. Thus, it breached the species barrier and was able to spread from poultry to humans [
14‐
16]. By retaining its ability to bind to α-2,3 linked sialic acid, the virus predominately replicated in the lower respiratory tract, limiting the efficacy of person-to-person spread [
17]. This dual receptor specificity allowed the virus to continue to circulate in poultry, including chickens and quails [
18,
19].
In the first four waves of the H7N9 outbreak, the cleavage site of the viral HA possessed only a single amino acid R (arginine), indicating a low pathogenic phenotype in poultry [
11,
20]. However, in viruses isolated from live poultry markets (LPM) in Guangdong province during the fifth wave, researchers found four amino acids (RKRT) inserted into the HA cleavage site (4 of 69 strains). This insertion was associated with the conversion of the virus from a low to high pathogenic phenotype in poultry [
21]. Moreover, an increased number of virus strains with a 588 V mutation in the PB2 were detected [
22]. The 588 V mutation has previously been associated with enhanced viral pathogenesis in mammalian species [
22,
23]. Indeed, there were at least 23 different genotypes of H7N9 influenza viruses detected by the end of December 2017. Among those, seven genotypes were genetically distinct, whilst 16 were found to have evolved from the 2013 H7N9 influenza viruses [
21]. Although the HPAI virus H7N9 was first isolated from LPMs in Guangdong, it is believed that the HPAI virus H7N9 originated from the Yangtze river delta and spread to the southeast coast via live poultry transactions [
24]. The HPAI virus H7N9 then evolved into multiple genotypes via reassortment with H9N2 influenza viruses and local low pathogenic H7N9 viruses [
24]. As of July 2017, the HPAI H7N9 influenza virus has spread to more than 12 different provinces in China [
24].