Herpes simplex virus-1 induces complement-mediated microglial phagocytosis of synapses in murine primary brain cultures and tissues.

Herpes simplex virus type 1 (HSV-1), a neurotropic and widespread pathogen, has been suggested as a potential risk factor for Alzheimer’s disease (AD), the most common form of dementia in elderly people. However, the molecular mechanisms triggered by the virus remain to be fully elucidated. Increasing evidence suggests that the innate immune system, particularly the complement cascade, plays a key role in early synapse loss, a hallmark of AD progression. Here, we demonstrate that HSV-1 infection of brain cells induces upregulation of complement components, promoting complement-dependent microglia engulfment, thus contributing to synaptic loss. Our results support a causative role of complement in HSV-1-induced synaptic pruning thus providing a novel understanding of how HSV-1 infection contributes to synaptic loss in AD.