HSV-1 infection induces brain cofilin hyperphosphorylation in the 5×FAD Alzheimer’s Disease mouse model

Alzheimer’s disease (AD) is a degenerative neurological disease characterized by various biological signatures, including synaptic dysfunction, β-amyloid plaques, hyperphosphorylated Tau, cofilin-actin rods, and Hirano bodies, all of which are linked to the actin cytoskeleton and its regulators. Additionally, the presence of herpes simplex virus type 1 (HSV-1) in the brains of AD patients has long been suggested as a contributing factor for AD. However, mechanisms by which HSV-1 accelerates AD pathogenesis remain poorly understood. Here we report that HSV-1 infection induces hyperphosphorylation of cofilin in the brains of 5×FAD mice. Cofilin is an actin depolymerizing factor, and its S3 phosphorylation inactivates cofilin’s activity to depolymerize actin filaments. These findings facilitate the understanding of impacts of HSV-1 infection on the development of Alzheimer’s disease and have implications in AD therapeutics.