AG Hosseini

Neuroinfectiology and Neuroinflammation

My research is centered on elucidating how acute and persistent viral infections impact the central nervous system (CNS) and contribute to both transient and long-term neurological dysfunction. Viral neuroinvasion, even when efficiently controlled, induces robust innate immune responses that can disrupt neuronal homeostasis. In cases of persistent or latent infection, low-level viral activity and sustained immune signaling may establish a chronic neuroinflammatory milieu, which is increasingly recognized as a key driver of progressive synaptic and cognitive alterations, particularly in the aging brain.

A major focus of my work is the role of microglial cells as critical mediators at the interface of immunity and neural circuit regulation. Microglia are highly dynamic cells that continuously monitor the CNS microenvironment and contribute to synaptic remodeling through activity-dependent synaptic pruning. This process is tightly regulated under physiological conditions and involves molecular pathways such as complement-mediated tagging of synapses (e.g., C1q and C3) and subsequent phagocytic elimination. However, during viral infection, microglia undergo profound phenotypic and functional changes in response to pathogen-associated signals and inflammatory cytokines.

I am particularly interested in how infection-induced microglial activation alters synaptic pruning mechanisms, potentially leading to excessive or aberrant elimination of functional synapses. Emerging evidence suggests that viral infections can amplify complement signaling and disrupt the balance between synaptic maintenance and removal, thereby contributing to impaired neuronal connectivity. These effects are especially relevant in the hippocampus, a brain region essential for learning and memory and highly susceptible to inflammatory insults.

By integrating approaches from neuroimmunology and virology, my research aims to dissect the cellular and molecular mechanisms linking viral infection to synaptic dysfunction and cognitive decline. A deeper understanding of how microglia-mediated synaptic remodeling is modulated during acute versus persistent infection will provide critical insights into the pathogenesis of infection-associated neurological disorders and may reveal novel therapeutic strategies to mitigate long-term consequences of neuroinflammation.