H7N7 avian influenza viruses (AIVs) can evolve from low pathogenic (LPAI) to highly pathogenic (HPAI) forms, most often through acquisition of multibasic residues at the haemagglutinin (HA) cleavage site. Understanding how these transitions occur in poultry, and how hosts respond during early infection, is essential for improving surveillance and outbreak preparedness. This thesis examines the evolutionary, virological, and immunological differences between LPAI and HPAI H7N7 viruses circulating during European outbreaks in 2015. Two virus pairs were selected to represent distinct evolutionary stages: an early‑evolution pair reflecting a waterfowl‑to‑poultry host shift (A/mallard/Netherlands/19/2015 LPAI and A/chicken/England/26352/2015 HPAI) and a late‑evolution pair representing a confirmed LPAI‑to‑HPAI transition on a single poultry premises (A/chicken/Germany/AR915/2015 LPAI and A/chicken/Germany/AR1385/2015 HPAI).

Viruses were propagated in embryonated eggs and cell culture, and infections were conducted both in vivo (chickens) and in vitro (chicken and duck embryo fibroblasts). Viral replication dynamics, tissue distribution, histopathological changes, antigen localisation, and innate immune gene expression were assessed across multiple tissues and timepoints. Genomic and phylogenetic analyses further characterised evolutionary relationships among circulating H7N7 viruses.

Across both evolutionary pairs, LPAIV and HPAIV infections produced broadly similar early innate immune activation profiles and comparable replication patterns in several tissues. However, HPAIV strains showed more consistent systemic dissemination. Detection of viral RNA in the brains of some LPAI‑infected chickens suggests transient neurotropism or the presence of intermediate evolutionary phenotypes. In vitro studies revealed species‑specific fibroblast responses but no major differences between LPAIV and HPAIV within each matched pair.

Overall, the findings suggest that the emergence of HPAI H7N7 is driven by subtle genetic changes interacting with host‑specific factors, rather than dramatic phenotypic shifts detectable early in infection. This work advances understanding of the molecular and immunological determinants shaping H7N7 evolution and pathogenicity in avian hosts.