Influenza in humans is mainly caused by two different viruses: influenza A virus (IAV) and influenza B virus. Beyond humans, IAV infects a broader range of species, including avian, equine, porcine and canine species. In contrast, influenza B virus almost exclusively infects humans. Avian IAVs are categorised in two main ways: by subtype and by pathotype. Subtyping is based on the diversity of the two major surface proteins: haemagglutinin (HA) and neuraminidase (NA). These proteins are highly diverse, with 19 HA subtypes and 11 NA subtypes, where the HA-NA combination added together make up the basic identity tag, or subtype, for example, H1N1 and H5N1. To date, only three IAV subtypes have emerged in human populations as pandemic or epidemic viruses over the last century (H1N1, H3N2 and H2N2). Within some HA subtypes, such as H5, viruses may be further characterised into clades based on genetic differences in their HA, somewhat similar to “variants” in SARS-CoV-2.
Pathotyping is based on pathogenicity in chickens. Low pathogenicity avian influenza viruses, which are frequently found in wild waterbirds, the natural reservoir for these viruses, generally cause no clinical disease in them or other wild birds. Following introduction into poultry, H5 and H7 avian IAVs may evolve and become highly virulent, causing high levels of mortality in poultry (up to 100% in chickens). Consequently, these viruses are referred to as high pathogenicity avian influenza (HPAI) viruses.