No evidence for aberrant expression of amyloid β and phosphorylated tau proteins in herpes simplex virus-infected human neurons in vivo

ABSTRACT Increasing evidence implicates the 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 in trigeminal ganglia was identical between AD patients and controls, and latently HSV-infected neurons did not express amyloid β (Aβ) or hyperphosphorylated tau (pTau). Some HSE patient brains presented with ageing-related intraneuronal Aβ accumulations, neurofibrillary tangles (NFT) or extracellular Aβ plaques, 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 Aβ plaques and NFT, but did not exacerbate AD-related pathology in relation to HSV infection. HSE-associated neuroinflammation was not associated with specific Aβ or pTau phenotypes. Collectively, the data indicate that neither latent nor lytic HSV infection of human neurons in vivo is directly associated with aberrant Aβ or pTau protein expression.