PMID- 20573821
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 84
IP  - 17
DP  - 2010 Sep
TI  - Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a 
      true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in 
      the trigeminal ganglion.
PG  - 8811-20
LID - 10.1128/JVI.00496-10 [doi]
AB  - Following herpes simplex virus type 1 (HSV-1) ocular infection of C57BL/6 mice, 
      activated CD8(+) T cells specific for an immunodominant epitope on HSV-1 
      glycoprotein B (gB-CD8 cells) establish a stable memory population in HSV-1 
      latently infected trigeminal ganglia (TG), whereas non-HSV-specific CD8(+) T 
      cells are lost over time. The retention and activation of gB-CD8 cells appear to 
      be influenced by persistent viral antigenic exposure within the latently infected 
      TG. We hypothesized that the low-level expression of gB from its native promoter 
      before viral DNA synthesis is critical for the retention and activation of gB-CD8 
      cells in the TG during HSV-1 latency and for their ability to block HSV-1 
      reactivation from latency. To test this, we created a recombinant HSV-1 in which 
      gB is expressed only after viral DNA synthesis from the true late gC promoter 
      (gCp-gB). Despite minor growth differences compared to its rescuant in infected 
      corneas, gCp-gB was significantly growth impaired in the TG and produced a 
      reduced latent genome load. The gCp-gB- and rescuant-infected mice mounted 
      similar gB-CD8 effector responses, but the size and activation phenotypes of the 
      memory gB-CD8 cells were diminished in gCp-gB latently infected TG, suggesting 
      that the stimulation of gB-CD8 cells requires gB expression before viral DNA 
      synthesis. Surprisingly, late gB expression did not compromise the capacity of 
      gB-CD8 cells to inhibit HSV-1 reactivation from latency in ex vivo TG cultures, 
      suggesting that gB-CD8 cells can block HSV-1 reactivation at a very late stage in 
      the viral life cycle. These data have implications for designing better 
      immunogens for vaccines to prevent HSV-1 reactivation.
FAU - Ramachandran, Srividya
AU  - Ramachandran S
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, Pennsylvania 15213, USA.
FAU - Davoli, Katherine A
AU  - Davoli KA
FAU - Yee, Michael B
AU  - Yee MB
FAU - Hendricks, Robert L
AU  - Hendricks RL
FAU - Kinchington, Paul R
AU  - Kinchington PR
LA  - eng
GR  - EY08098/EY/NEI NIH HHS/United States
GR  - EY05945/EY/NEI NIH HHS/United States
GR  - EY015291/EY/NEI NIH HHS/United States
GR  - P30 EY008098/EY/NEI NIH HHS/United States
GR  - R01 EY005945/EY/NEI NIH HHS/United States
GR  - R01 EY015291/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100623
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (glycoprotein B, Simplexvirus)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology/virology
MH  - Chlorocebus aethiops
MH  - Female
MH  - *Gene Expression Regulation, Viral
MH  - Herpes Simplex/genetics/*immunology/virology
MH  - Herpesvirus 1, Human/genetics/immunology/*pathogenicity
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Trigeminal Ganglion/*immunology/virology
MH  - Vero Cells
MH  - Viral Envelope Proteins/*genetics/immunology
MH  - Virulence
PMC - PMC2919033
EDAT- 2010/06/25 06:00
MHDA- 2010/09/18 06:00
PMCR- 2011/03/01
CRDT- 2010/06/25 06:00
PHST- 2010/06/25 06:00 [entrez]
PHST- 2010/06/25 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - JVI.00496-10 [pii]
AID - 0496-10 [pii]
AID - 10.1128/JVI.00496-10 [doi]
PST - ppublish
SO  - J Virol. 2010 Sep;84(17):8811-20. doi: 10.1128/JVI.00496-10. Epub 2010 Jun 23.