PMID- 26912623
OWN - NLM
STAT- MEDLINE
DCOM- 20160825
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 9
DP  - 2016 May
TI  - Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in 
      Sensory Neurons.
PG  - 4706-4719
LID - 10.1128/JVI.02908-15 [doi]
AB  - Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of 
      trigeminal ganglia (TG), cycling between productive infection and latency. 
      Neuronal antiviral responses are driven by type I interferon (IFN) and are 
      crucial to controlling HSV-1 virulence. Autophagy also plays a role in this 
      neuronal antiviral response, but the mechanism remains obscure. In this study, 
      HSV-1 infection of murine TG neurons triggered unusual clusters of 
      autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. 
      Treatment of neurons with IFN-beta induced a similar response, and cluster formation 
      by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. 
      The autophagic clusters were decorated with both ISG15, an essential effecter of 
      the antiviral response, and p62, a selective autophagy receptor. The autophagic 
      clusters were not induced by rapamycin or starvation, consistent with a process 
      of selective autophagy. While clusters were triggered by other neurotropic 
      herpesviruses, infection with unrelated viruses failed to induce this response. 
      Following ocular infection in vivo, clusters formed exclusively in the infected 
      ophthalmic branch of the TG. Taken together, our results show that infection with 
      HSV and antiviral signaling in TG neurons produce an unorthodox autophagic 
      response. This autophagic clustering is associated with antiviral signaling, the 
      presence of viral genome, and the absence of HSV protein expression and may 
      therefore represent an important neuronal response to HSV infection and the 
      establishment of latency. IMPORTANCE: Herpes simplex virus type 1 (HSV-1) is a 
      ubiquitous virus and a significant cause of morbidity and some mortality. It is 
      the causative agent of benign cold sores, but it can also cause blindness and 
      life-threatening encephalitis. The success of HSV-1 is largely due to its ability 
      to establish lifelong latent infections in neurons and to occasionally 
      reactivate. The exact mechanisms by which neurons defend against virus infection 
      is poorly understood, but such defense is at least partially mediated by 
      autophagy, an intracellular pathway by which pathogens and other unwanted cargoes 
      are degraded. The study demonstrates and investigates a new autophagic structure 
      that appears to be specific to the interaction between neurotropic herpesviruses 
      and murine primary sensory neurons. This work may therefore have important 
      implications for our understanding of latency and reactivation.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Katzenell, Sarah
AU  - Katzenell S
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  - 2T32AI007363-21A1/AI/NIAID NIH HHS/United States
GR  - P20 RR016437/RR/NCRR NIH HHS/United States
GR  - EY09083/EY/NEI NIH HHS/United States
GR  - R01 EY009083/EY/NEI NIH HHS/United States
GR  - P01 AI098681/AI/NIAID NIH HHS/United States
GR  - AI098681/AI/NIAID NIH HHS/United States
GR  - T32 AI007363/AI/NIAID NIH HHS/United States
GR  - P30RR016437/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160414
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 77238-31-4 (Interferon-beta)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Genes, Reporter
MH  - Herpes Simplex/*metabolism/*virology
MH  - Herpesvirus 1, Human/*physiology
MH  - Interferon-beta/metabolism
MH  - Interferons/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Phagosomes/metabolism
MH  - Sensory Receptor Cells/*metabolism/*virology
MH  - *Signal Transduction
MH  - Virus Replication
PMC - PMC4836354
EDAT- 2016/02/26 06:00
MHDA- 2016/08/26 06:00
PMCR- 2016/10/14
CRDT- 2016/02/26 06:00
PHST- 2015/11/18 00:00 [received]
PHST- 2016/02/19 00:00 [accepted]
PHST- 2016/02/26 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2016/08/26 06:00 [medline]
PHST- 2016/10/14 00:00 [pmc-release]
AID - JVI.02908-15 [pii]
AID - 02908-15 [pii]
AID - 10.1128/JVI.02908-15 [doi]
PST - epublish
SO  - J Virol. 2016 Apr 14;90(9):4706-4719. doi: 10.1128/JVI.02908-15. Print 2016 May.