Influenza A virus (IAV) infection can lead to cerebral manifestations, potentially increasing the risk for neurodegenerative diseases. Some IAV strains, such as avian H7N7 subtype, are neurotropic and capable of invading and infecting resident cells in the brain. IAV-induced production of proinflammatory cytokines leads to activation of microglia, thereby potentially triggering neuronal damage and dysfunction. Microglial characteristics such as phagocytosis rate, activity and morphology are sex-dependent. Therefore, a better understanding of IAV neurotropism and the mechanisms leading to deleterious neurological manifestations in a sex-specific manner is of great importance. Here, we performed in vitro experiments using primary hippocampal cultures from male and female mice. To analyze the role of microglia and to be closer to the hippocampal physiology, we added microglia of the respective sex to the cultures. In this project, we aim to characterize the neuropathological mechanisms of IAV infection in detail. Three distinct microglial morphology types with sex-specific densities, including ramified, bushy, and amoeboid forms, were observed in female and male cultures following IAV infection. In cultures prepared from male mice, a lower infection rate compared to cultures derived from females were observable. To further characterize the neurovirulence of H7N7 IAV, we are currently investigating synaptic stripping by analyzing neuronal spine density as well as the frequency of dendritic spine types following H7N7 IAV infection. The results of this study may pave the way for a better understanding of the mechanisms involved in the immediate and long-term neurological consequences of IAV infection to develop appropriate prevention strategies.