High pathogenicity avian influenza virus emergence: Blame it on chickens or on humans raising chickens?

Low pathogenicity avian influenza viruses (LPAIV) of H5 and H7 subtypes can naturally evolve to replicate systemically in birds, acquiring a high pathogenicity avian influenza virus (HPAIV) phenotype. As well as having a considerable impact in veterinary medicine, HPAIVs jeopardize food safety and public health because of their zoonotic potential. A number of genetic mechanisms have been identified as being responsible for the evolution from LPAIV to HPAIV. The determinant change is the acquisition of a furin-like protease-dependent hemagglutinin multibasic cleavage site (MBCS), via non-synonymous nucleotide substitutions, nucleotide insertions, or recombination with cellular or viral RNAs caused by viral polymerase template switching. In addition, other mutations in the hemagglutinin and other viral gene segments are sometimes required for the acquisition of a high pathogenicity phenotype. The molecular mechanisms underlying genetic changes leading to HPAIV emergence, including its restriction to H5 and H7 subtypes, will not be discussed further, as the aim of this article is to provide a multi-faceted analysis of the role of the host in the emergence of HPAIV. It is commonly accepted that conversion from LPAIV to HPAIV occurs in terrestrial poultry belonging to the Galliformes order, particularly in chickens and turkeys. In the following sections of this article, we will describe supporting evidence for a decisive role of Galliformes in HPAIV emergence, and also delineate the factors that could promote HPAIV emergence in Galliformes compared to other bird species.