PMID- 30728262
OWN - NLM
STAT- MEDLINE
DCOM- 20200128
LR  - 20200309
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 8
DP  - 2019 Apr 15
TI  - Infectious Herpes Simplex Virus in the Brain Stem Is Correlated with Reactivation 
      in the Trigeminal Ganglia.
LID - 10.1128/JVI.02209-18 [doi]
LID - e02209-18
AB  - Herpes simplex virus (HSV) establishes latency in neurons of the peripheral and 
      central nervous systems (CNS). Evidence is mounting that HSV latency and 
      reactivation in the nervous system has the potential to promote neurodegenerative 
      processes. Understanding how this occurs is an important human health goal. In 
      the mouse model, in vivo viral reactivation in the peripheral nervous system, 
      triggered by hyperthermic stress, has been well characterized with respect to 
      frequency and cell type. However, characterization of in vivo reactivation in the 
      CNS is extremely limited. Further, it remains unclear whether virus reactivated 
      in the peripheral nervous system is transported to the CNS in an infectious form, 
      how often this occurs, and what parameters underlie the efficiency and outcomes 
      of this process. In this study, reactivation was quantified in the trigeminal 
      ganglia (TG) and the brain stem from the same latently infected animal using 
      direct assays of equivalent sensitivity. Reactivation was detected more 
      frequently in the TG than in the brain stem and, in all but one case, the amount 
      of virus recovered was greater in the TG than that detected in the brain stem. 
      Viral protein positive neurons were observed in the TG, but a cellular source for 
      reactivation in the brain stem was not identified, despite serially sectioning 
      and examining the entire tissue (0/6 brain stems). These findings suggest that 
      infectious virus detected in the brain stem is primarily the result of transport 
      of reactivated virus from the TG into the brain stem.IMPORTANCE Latent herpes 
      simplex virus (HSV) DNA has been detected in the central nervous systems (CNS) of 
      humans postmortem, and infection with HSV has been correlated with the 
      development of neurodegenerative diseases. However, whether HSV can directly 
      reactivate in the CNS and/or infectious virus can be transported to the CNS 
      following reactivation in peripheral ganglia has been unclear. In this study, 
      infectious virus was recovered from both the trigeminal ganglia and the brain 
      stem of latently infected mice following a reactivation stimulus, but a higher 
      frequency of reactivation and increased titers of infectious virus were recovered 
      from the trigeminal ganglia. Viral proteins were detected in neurons of the 
      trigeminal ganglia, but a cellular source of infectious virus could not be 
      identified in the brain stem. These results suggest that infectious virus is 
      transported from the ganglia to the CNS following reactivation but do not exclude 
      the potential for direct reactivation in the CNS.
CI  - Copyright (c) 2019 Doll et al.
FAU - Doll, Jessica R
AU  - Doll JR
AUID- ORCID: 0000-0001-5225-801X
AD  - University of Cincinnati, Department of Molecular Genetics, Biochemistry, and 
      Microbiology, Cincinnati, Ohio, USA jessica.doll@cchmc.org.
AD  - Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, 
      Cincinnati, Ohio, USA.
FAU - Thompson, Richard L
AU  - Thompson RL
AD  - University of Cincinnati, Department of Molecular Genetics, Biochemistry, and 
      Microbiology, Cincinnati, Ohio, USA.
FAU - Sawtell, Nancy M
AU  - Sawtell NM
AD  - Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, 
      Cincinnati, Ohio, USA.
LA  - eng
GR  - R01 AI093614/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190403
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Animals
MH  - Biological Transport, Active
MH  - Brain Stem/*metabolism/pathology/virology
MH  - Female
MH  - Herpes Simplex/*metabolism/pathology
MH  - Herpesvirus 1, Human/*physiology
MH  - Male
MH  - Mice
MH  - Rabbits
MH  - Trigeminal Ganglion/*metabolism/pathology/virology
MH  - Viral Proteins/*metabolism
MH  - Virus Activation/*physiology
MH  - Virus Latency/*physiology
PMC - PMC6450102
OTO - NOTNLM
OT  - hypercellular cuff
OT  - hyperthermic stress
OT  - in vivo reactivation
OT  - mouse ocular model
OT  - sensory neuron
OT  - viral latency
OT  - virus recovery
EDAT- 2019/02/08 06:00
MHDA- 2020/01/29 06:00
PMCR- 2019/04/03
CRDT- 2019/02/08 06:00
PHST- 2018/12/12 00:00 [received]
PHST- 2019/01/23 00:00 [accepted]
PHST- 2019/02/08 06:00 [pubmed]
PHST- 2020/01/29 06:00 [medline]
PHST- 2019/02/08 06:00 [entrez]
PHST- 2019/04/03 00:00 [pmc-release]
AID - JVI.02209-18 [pii]
AID - 02209-18 [pii]
AID - 10.1128/JVI.02209-18 [doi]
PST - epublish
SO  - J Virol. 2019 Apr 3;93(8):e02209-18. doi: 10.1128/JVI.02209-18. Print 2019 Apr 
      15.