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

Increasing evidence implicates the neurotropic herpes simplex virus 1 (HSV-1) in the pathogenesis of Alzheimers 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 {beta} (A{beta}) or hyperphosphorylated tau (pTau). Some HSE patient brains presented with ageing-related intraneuronal A{beta} accumulations, neurofibrillary tangles (NFT) or extracellular A{beta} 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 A{beta} plaques and NFT, but did not exacerbate AD-related pathology in relation to HSV infection. HSE-associated neuroinflammation was not associated with specific A{beta} or pTau phenotypes. Collectively, the data indicate that neither latent nor lytic HSV infection of human neurons in vivo is directly associated with aberrant A{beta} or pTau protein expression.