TY - JOUR
T1 - No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain
AU - Tran, Diana N.
AU - Bakx, Amy T. C. M.
AU - van Dis, Vera
AU - Aronica, Eleonora
AU - Verdijk, Robert M.
AU - Ouwendijk, Werner J. D.
N1 - Funding Information: We thank Dr. Georges Verjans for the critical discussion of the data and Tamana Khemai‐Mehraban for technical assistance. Research reported in this publication was in part supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI151290 (W.J.D.O.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was funded in part by a Human Disease Model Award 2020 (Erasmus MC). Publisher Copyright: © 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
PY - 2021
Y1 - 2021
N2 - 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 β (Aβ) and hyperphosphorylated tau (pTau) were not detected in latently HSV-infected TG neurons. Aging-related intraneuronal Aβ accumulations, neurofibrillary tangles (NFT), and/or extracellular Aβ 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 Aβ plaques and NFT, but were not associated with exacerbated AD-related pathology. HSE-associated neuroinflammation was not associated with specific Aβ or pTau phenotypes. Collectively, we observed that neither latent nor lytic HSV infection of human neurons is directly associated with aberrant Aβ or pTau protein expression in ganglia and brain.
AB - 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 β (Aβ) and hyperphosphorylated tau (pTau) were not detected in latently HSV-infected TG neurons. Aging-related intraneuronal Aβ accumulations, neurofibrillary tangles (NFT), and/or extracellular Aβ 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 Aβ plaques and NFT, but were not associated with exacerbated AD-related pathology. HSE-associated neuroinflammation was not associated with specific Aβ or pTau phenotypes. Collectively, we observed that neither latent nor lytic HSV infection of human neurons is directly associated with aberrant Aβ or pTau protein expression in ganglia and brain.
KW - Alzheimer's disease
KW - amyloid β
KW - herpes simplex encephalitis
KW - herpes simplex virus
KW - neurofibrillary tangles
KW - varicella-zoster virus
UR - http://www.scopus.com/inward/record.url?scp=85121377682&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bpa.13044
DO - https://doi.org/10.1111/bpa.13044
M3 - Article
C2 - 34913212
SN - 1015-6305
JO - Brain pathology (Zurich, Switzerland)
JF - Brain pathology (Zurich, Switzerland)
ER -