Avian Influenza A Viruses: Evolution and Zoonotic Infection

Abstract

Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics.

Fig. 1

Reservoir of influenza viruses. It is known that wild aquatic birds are the source of all influenza viruses in other species. Although transmission between humans and pigs had already been demonstrated and confirmed, direct transmission of avian-to-humans have been less frequent (such as those with H9N2 and H5N1 subtypes) but sometimes with fatal outcome.

Fig. 2

Schematic diagram model of multiple reassortment events of human infected novel influenza viruses from avian (H7N9, H10N8 and H6N1). The colors of the eight gene segments in the ovals represent origin viruses. As the diagram show, same colors is same linage (H9N2) and different colors is different viruses.

Fig. 3

Pigs promote the generation of novel viruses with pandemic potential. Pigs are potential reservoir of old virus strains for subsequent infection of human populations. Avian influenza viruses that infect humans could undergo adaptation altering its receptor-binding affinity to those for human epithelial receptors. Lastly, coinfection of an avian and mammalian virus in a single host cell could generate novel virus genotypes (∼256 recombinant viruses could be generated from two parental viruses), one of which could cause the next pandemic.