PMID- 24942587
OWN - NLM
STAT- MEDLINE
DCOM- 20141212
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 17
DP  - 2014 Sep 1
TI  - Intrinsic innate immunity fails to control herpes simplex virus and vesicular 
      stomatitis virus replication in sensory neurons and fibroblasts.
PG  - 9991-10001
LID - 10.1128/JVI.01462-14 [doi]
AB  - Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the 
      sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity 
      to reactivate. The interferon (IFN)-driven antiviral response is critical for the 
      control of HSV-1 acute replication. We therefore sought to further investigate 
      this response in TG neurons cultured from adult mice deficient in a variety of 
      IFN signaling components. Parallel experiments were also performed in fibroblasts 
      isolated concurrently. We showed that HSV-1 replication was comparable in 
      wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, 
      a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus 
      (VSV). Despite these findings, TG neurons responded to IFN-beta pretreatment with 
      STAT1 nuclear localization and restricted replication of both VSV and an HSV-1 
      strain deficient in gamma34.5, while wild-type HSV-1 replication was unaffected. This 
      was in contrast to fibroblasts in which all viruses were restricted by the 
      addition of IFN-beta. Taken together, these data show that adult TG neurons can 
      mount an effective antiviral response only if provided with an exogenous source 
      of IFN-beta, and HSV-1 combats this response through gamma34.5. These results further 
      our understanding of the antiviral response of neurons and highlight the 
      importance of paracrine IFN-beta signaling in establishing an antiviral state. 
      IMPORTANCE: Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that establishes 
      a lifelong latent infection in neurons. Reactivation from latency can cause cold 
      sores, blindness, and death from encephalitis. Humans with deficiencies in innate 
      immunity have significant problems controlling HSV infections. In this study, we 
      therefore sought to elucidate the role of neuronal innate immunity in the control 
      of viral infection. Using neurons isolated from mice, we found that the intrinsic 
      capacity of neurons to restrict virus replication was unaffected by the presence 
      or absence of innate immunity. In contrast, neurons were able to mount a robust 
      antiviral response when provided with beta interferon, a molecule that strongly 
      stimulates innate immunity, and that HSV-1 can combat this response through the 
      gamma34.5 viral gene. Our results have important implications for understanding how 
      the nervous system defends itself against virus infections.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Rosato, Pamela C
AU  - Rosato PC
AD  - Department of Microbiology and Immunology, Geisel School of Medicine at 
      Dartmouth, Lebanon, New Hampshire, USA.
FAU - Leib, David A
AU  - Leib DA
AD  - Department of Microbiology and Immunology, Geisel School of Medicine at 
      Dartmouth, Lebanon, New Hampshire, USA david.a.leib@dartmouth.edu.
LA  - eng
GR  - P20 RR016437/RR/NCRR NIH HHS/United States
GR  - 5T32AI007519/AI/NIAID NIH HHS/United States
GR  - R01 EY009083/EY/NEI NIH HHS/United States
GR  - P20RR016437/RR/NCRR NIH HHS/United States
GR  - P01 AI098681/AI/NIAID NIH HHS/United States
GR  - R01 EY09083/EY/NEI NIH HHS/United States
GR  - T32 AI007519/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140618
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Animals
MH  - Fibroblasts/*immunology/*virology
MH  - *Immunity, Innate
MH  - Interferon-beta/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Sensory Receptor Cells/*immunology/*virology
MH  - Simplexvirus/*immunology/physiology
MH  - Vesiculovirus/*immunology/physiology
MH  - Virus Replication
PMC - PMC4136337
EDAT- 2014/06/20 06:00
MHDA- 2014/12/17 06:00
PMCR- 2015/03/01
CRDT- 2014/06/20 06:00
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - JVI.01462-14 [pii]
AID - 01462-14 [pii]
AID - 10.1128/JVI.01462-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Sep 1;88(17):9991-10001. doi: 10.1128/JVI.01462-14. Epub 2014 Jun 
      18.