EMERGENCE AND EVOLUTION OF REASSORTANT HIGHLY PATHOGENIC H5 AVIAN INFLUENZA VIRUSES

Abstract

Highly pathogenic avian influenza viruses have posed a continuous threat to public health due to zoonotic infection. Since they emerged, A/goose/Guangdong/1/1996-like (Gs/GD) H5 viruses were predominantly H5N1 subtype. In 2014, the clade 2.3.4.4 sublineage of Gs/GD with an array of different NA serotypes, including H5N6 and H5N8, emerged through virus reassortment, and have caused severe epidemics globally. This thesis aims to elucidate the process by which non-N1 subtype (H5Nx) viruses established sustained transmission in poultry. I first reconstructed the population dynamics of the three major H5N1 sublineages in their epicenter of mainland China prior to the global dissemination of H5Nx viruses. Next, I examined the HA and NA genes of H5Nx viruses in order to find adaptive signatures that may have occurred due to interactions between the HA (H5) and the newly acquired NA proteins, facilitating the emergence of the new subtypes. Lastly, I looked into the process where H5Nx viruses entered a previously unaffected area and developed endemic circulation in poultry. Collectively, the findings presented in this thesis show that human activities play an important role in the emergence and the evolution of H5Nx viruses, and also demonstrate divergent population behaviours among sublineages of Gs/GD H5N1/H5Nx viruses.