PMID- 16051826
OWN - NLM
STAT- MEDLINE
DCOM- 20050908
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 79
IP  - 16
DP  - 2005 Aug
TI  - Gamma interferon can block herpes simplex virus type 1 reactivation from latency, 
      even in the presence of late gene expression.
PG  - 10339-47
AB  - Herpes simplex virus type 1 (HSV-1)-specific CD8+ T cells and the cytokine gamma 
      interferon (IFN-gamma) are persistently present in trigeminal ganglia (TG) 
      harboring latent HSV-1. We define "latency" as the retention of functional viral 
      genomes in sensory neurons without the production of infectious virions and 
      "reactivation" as a multistep process leading from latency to virion assembly. 
      CD8+ T cells can block HSV-1 reactivation in ex vivo mouse TG cultures and appear 
      to be the sole source of IFN-gamma in these cultures. Here we demonstrate that 
      IFN-gamma alone can block HSV-1 reactivation in some latently infected neurons, 
      and we identify points of intervention in the life cycle of the reactivating 
      virus. Cell suspensions of TG that were latently infected with recombinant RE 
      HSV-1 expressing enhanced green fluorescent protein from the promoter for 
      infected cell protein 0 (ICP0) or glycoprotein C (gC) were depleted of endogenous 
      CD8+ or CD45+ cells and cultured in the presence or absence of IFN-gamma. Our 
      results demonstrate that IFN-gamma acts on latently infected neurons to inhibit 
      (i) HSV-1 reactivation, (ii) ICP0 promoter activity, (iii) gC promoter activity, 
      and (iv) reactivation in neurons in which the ICP0 or gC promoter is active. 
      Interestingly, we detected transcripts for ICP0, ICP4, and gH in neurons that 
      expressed the ICP0 promoter but were prevented by IFN-gamma from reactivation and 
      virion formation. Thus, the IFN-gamma blockade of HSV-1 reactivation from latency 
      in neurons is associated with an inhibition of the expression of the ICP0 gene 
      (required for reactivation) and a blockade of a step that occurs after the 
      expression of at least some viral structural genes.
FAU - Decman, Vilma
AU  - Decman V
AD  - University of Pittsburgh, Department of Ophthalmology, 203 Lothrop Street, 
      Pittsburgh, PA 15213, USA.
FAU - Kinchington, Paul R
AU  - Kinchington PR
FAU - Harvey, Stephen A K
AU  - Harvey SA
FAU - Hendricks, Robert L
AU  - Hendricks RL
LA  - eng
GR  - R01 EY005945/EY/NEI NIH HHS/United States
GR  - R01 EY015291/EY/NEI NIH HHS/United States
GR  - EY008098/EY/NEI NIH HHS/United States
GR  - EY005945/EY/NEI NIH HHS/United States
GR  - EY015291/EY/NEI NIH HHS/United States
GR  - P30 EY008098/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 0 (Immediate-Early Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Vmw110 protein, Human herpesvirus 1)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Female
MH  - Herpesvirus 1, Human/*drug effects/genetics/physiology
MH  - Immediate-Early Proteins/genetics
MH  - Interferon-gamma/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Promoter Regions, Genetic
MH  - Ubiquitin-Protein Ligases
MH  - Virus Activation/*drug effects
MH  - Virus Latency
MH  - Virus Replication/drug effects
PMC - PMC1182646
EDAT- 2005/07/30 09:00
MHDA- 2005/09/09 09:00
PMCR- 2005/08/01
CRDT- 2005/07/30 09:00
PHST- 2005/07/30 09:00 [pubmed]
PHST- 2005/09/09 09:00 [medline]
PHST- 2005/07/30 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - 79/16/10339 [pii]
AID - 0455-05 [pii]
AID - 10.1128/JVI.79.16.10339-10347.2005 [doi]
PST - ppublish
SO  - J Virol. 2005 Aug;79(16):10339-47. doi: 10.1128/JVI.79.16.10339-10347.2005.