Viral modulation of synaptic pruning: implications for neuropathology and brain function

Synaptic pruning is an essential neurodevelopmental process that refines neural circuits by eliminating superfluous or weak synapses, thereby enhancing cognitive functions, including learning and memory. Emerging evidence indicates that viral infections can profoundly influence synaptic processes throughout the nervous system. Viral pathogens have been shown to disrupt synaptic plasticity, alter synaptic protein expression, and dysregulate mechanisms responsible for synaptic elimination. These disruptions are often mediated through the activation of the complement system, inflammatory cytokines, and aberrant expression of postsynaptic density proteins. Depending on the nature and extent of infection, viral interference with synaptic pruning may result in either excessive synapse loss or synaptic retention, both of which are implicated in neuropathological outcomes, such as cognitive decline and neurodevelopmental disorders. This review examines the molecular and cellular mechanisms of synaptic pruning and highlights the impact of various neurotropic viruses on these processes. By elucidating the interplay between viral infections and synaptic pruning, we aim to provide insights into virus-associated neuropathology and inform future research directions and therapeutic strategies in the context of virology and neuroimmunology.