Role of exosomes in HSV-1-driven neuronal damage

Introduction: Several evidence, including those from our group, support the role of Herpes Simplex Virus-1 (HSV-1) infection in Alzheimer disease (AD) pathogenesis, a neurodegenerative disorder characterized by the accumulation of misfolded proteins in the brain such as beta-amyloid peptides (Abeta) and neurofibrillary tangles. These are mainly composed by hyperphosphorylated forms of tau (ptau), an intracellular protein able to bind and stabilize microtubules only when in unphosphorylated-native form. Recent studies have demonstrated transfer of Abeta and spread of tau/ptau between neurons in the brain of transgenic mouse models of AD, indicating that these pathological proteins can be propagated in the brain. Specifically, these proteins have been found in neuron-derived exosomes, small extracellular vesicles that recently emerged as key players in cellular communication in both health and diseases, including viral infections. Herein, we investigated whether HSV-1 infection in the brain could promote tau spreading among neurons via exosomes.