Pathological evidence of neurotropism and oculotropism in wild black-headed gulls naturally infected with H5N1 high pathogenicity avian influenza.

Clade 2.3.4.4b H5Nx high pathogenicity avian influenza viruses (HPAIVs) have caused extensive mortality in wild birds, particularly colonial seabirds, since 2020. Among them, black-headed gulls (Chroicocephalus ridibundus) are abundant, synanthropic birds widely distributed across Europe and northern Asia that exploit diverse habitats, raising questions about their role in AIVs ecology. Recent field observations have reported post-HPAI ocular abnormalities in some marine birds, suggesting a potential contribution of the eye to disease expression. However, the nature of these changes, viral tissue distribution and the underlying pathogenesis remain unclear. To address this, 13 black-headed gulls from a cohort of 49 confirmed HPAI cases in France underwent clinico-pathological assessment, immunohistochemistry and molecular analysis. Affected birds commonly exhibited emaciation and central neurological signs. Histopathology and immunostaining revealed marked neurotropism and consistent involvement of intraocular structures, including anterior uveitis and retinal degeneration. Viral antigen was detected in neuronal tissue, visceral and integumentary epithelial cells, with no evidence of endotheliotropism. This pattern resembles that reported in domestic ducks and may influence viral diffusion, persistence, intra- and interspecific transmissions. Our results suggest the eye is an underestimated target organ in HPAI infection, and provide new insights into the pathogenesis of HPAI-induced ocular abnormalities in seabirds.