PMID- 34913212
OWN - NLM
STAT- MEDLINE
DCOM- 20220628
LR  - 20220718
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 32
IP  - 4
DP  - 2022 Jul
TI  - No evidence of aberrant amyloid beta and phosphorylated tau expression in herpes 
      simplex virus-infected neurons of the trigeminal ganglia and brain.
PG  - e13044
LID - 10.1111/bpa.13044 [doi]
LID - e13044
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 beta (Abeta) and hyperphosphorylated tau (pTau) were not 
      detected in latently HSV-infected TG neurons. Aging-related intraneuronal Abeta 
      accumulations, neurofibrillary tangles (NFT), and/or extracellular Abeta 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 Abeta plaques and NFT, 
      but were not associated with exacerbated AD-related pathology. HSE-associated 
      neuroinflammation was not associated with specific Abeta or pTau phenotypes. 
      Collectively, we observed that neither latent nor lytic HSV infection of human 
      neurons is directly associated with aberrant Abeta or pTau protein expression in 
      ganglia and brain.
CI  - (c) 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf 
      of International Society of Neuropathology.
FAU - Tran, Diana N
AU  - Tran DN
AD  - Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, the 
      Netherlands.
FAU - Bakx, Amy T C M
AU  - Bakx ATCM
AD  - Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, the 
      Netherlands.
FAU - van Dis, Vera
AU  - van Dis V
AD  - Department of Pathology, Erasmus MC, University Medical Center Rotterdam, the 
      Netherlands.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
FAU - Verdijk, Robert M
AU  - Verdijk RM
AD  - Department of Pathology, Erasmus MC, University Medical Center Rotterdam, the 
      Netherlands.
FAU - Ouwendijk, Werner J D
AU  - Ouwendijk WJD
AUID- ORCID: 0000-0001-8393-296X
AD  - Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, the 
      Netherlands.
LA  - eng
GR  - R01 AI151290/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211216
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (MAPT protein, human)
RN  - 0 (tau Proteins)
SB  - IM
MH  - *Alzheimer Disease
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - *Herpes Simplex/metabolism
MH  - *Herpesvirus 1, Human/metabolism
MH  - Humans
MH  - Neurons/metabolism
MH  - Plaque, Amyloid
MH  - Trigeminal Ganglion/metabolism
MH  - tau Proteins/*metabolism
PMC - PMC9245940
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - amyloid beta
OT  - herpes simplex encephalitis
OT  - herpes simplex virus
OT  - neurofibrillary tangles
OT  - varicella-zoster virus
COIS- The authors have no conflicts of interest to declare.
EDAT- 2021/12/17 06:00
MHDA- 2022/06/29 06:00
PMCR- 2021/12/16
CRDT- 2021/12/16 06:47
PHST- 2021/11/26 00:00 [revised]
PHST- 2021/09/27 00:00 [received]
PHST- 2021/12/03 00:00 [accepted]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2022/06/29 06:00 [medline]
PHST- 2021/12/16 06:47 [entrez]
PHST- 2021/12/16 00:00 [pmc-release]
AID - BPA13044 [pii]
AID - 10.1111/bpa.13044 [doi]
PST - ppublish
SO  - Brain Pathol. 2022 Jul;32(4):e13044. doi: 10.1111/bpa.13044. Epub 2021 Dec 16.