No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain

Increasing evidence supports the role of neurotropic herpes simplex virus 1 (HSV-1) in the pathogenesis of Alzheimer's disease (AD). However, it is unclear whether previously reported findings in HSV-1 cell culture and animal models can be translated to humans. Here, we analyzed clinical specimens from latently HSV-1 infected individuals and individuals with lytic HSV infection of the brain (herpes simplex encephalitis; HSE). Latent HSV-1 DNA load and latency-associated transcript (LAT) expression were identical between trigeminal ganglia (TG) of AD patients and controls. Amyloid p (Am and hyperphosphorylated tau (pTau) were not detected in latently HSV-infected TG neurons. Aging-related intraneuronal A beta accumulations, neurofibrillary tangles (NFT), and/or extracellular A beta plaques were observed in the brain of some HSE patients, but these were neither restricted to HSV-infected neurons nor brain regions containing virus-infected cells. Analysis of unique brain material from an AD patient with concurrent HSE showed that HSV-infected cells frequently localized close to A beta plaques and NFT, but were not associated with exacerbated AD-related pathology. HSE-associated neuroinflammation was not associated with specific A beta or pTau phenotypes. Collectively, we observed that neither latent nor lytic HSV infection of human neurons is directly associated with aberrant A beta or pTau protein expression in ganglia and brain.

Automated summary

The findings suggest that latent or lytic HSV infection in human neurons is not directly associated with aberrant A beta or pTau protein expression. Some aging-related abnormalities were observed in the brains of HSE patients, but they were not limited to HSV-infected cells or brain regions.