Herpes Simplex Virus -1 (HSV-1) and Alzheimer’s disease: more than a hypothesis

Description

Abstract HSV is a DNA virus causing life-long latent infection in humans with multiple reactivations. Starting from the pioneering studies showing evidence of HSV-1 genome in Alzheimer’s disease (AD) brains, a growing body of epidemiological and experimental reports have proposed a possible connection between AD risk and HSV-1 recurrent infections. However, a cause-effect relationship between virus reactivations and this disorder has yet to be definitely proved. For this reason, we investigated a mouse model of recurrent HSV-1 infection for the appearance over time of AD markers, including brain accumulation of amyloid-β and hyperphosphorylated tau proteins, oxidative damages and neuroinflammation. Biochemical analysis of mouse brains revealed that multiple HSV-1 reactivations induced all these hallmarks. Specific oxidative damages were: increased levels of 4-hydroxynonenal (HNE, marker of lipid peroxidation), protein nytrosylation and carboxylation; alteration in the level of 13 HNE-modified proteins involved in important intracellular processes, suggesting that their oxidation may affect brain physiology. Finally, behavioral tests evidenced cognitive deficits that increased with multiple virus reactivations. Overall, our data suggest that recurrent HSV-1 infections concur to AD neurodegeneration also through oxidative damages.