PMID- 21307196
OWN - NLM
STAT- MEDLINE
DCOM- 20110614
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 9
DP  - 2011 May
TI  - The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice 
      latently infected with herpes simplex virus 1.
PG  - 4184-97
LID - 10.1128/JVI.02290-10 [doi]
AB  - Herpes simplex virus (HSV) infection is a classic example of latent viral 
      infection in humans and experimental animal models. The HSV-1 latency-associated 
      transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and 
      thus in recurrent disease. Whether the presence of LAT leads to generation of 
      dysfunctional T cell responses in the trigeminal ganglia (TG) of latently 
      infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] 
      and LAT-deficient [LAT(-)] viruses to evaluate the effect of LAT on CD8 T cell 
      exhaustion in TG of latently infected mice. The amount of latency as determined 
      by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG 
      extracts was 3-fold higher with LAT(+) than with LAT(-) virus. LAT expression and 
      increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. 
      PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, 
      and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) 
      TG contain both more CD8(+) T cells and more CD8(+) T cells expressing the 
      exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses 
      of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8(+) T cell pentamer (specific for 
      a peptide derived from residues 498 to 505 of glycoprotein B [gB(498-505)]), 
      interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha). The functional 
      significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the 
      significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. 
      Together, these results may suggest that both PD-1 and Tim-3 are mediators of 
      CD8(+) T cell exhaustion and latency in HSV-1 infection.
FAU - Allen, Sariah J
AU  - Allen SJ
AD  - Center for Neurobiology and Vaccine Development, D2024, Cedars-Sinai Burns and 
      Allen Research Institute, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
FAU - Hamrah, Pedram
AU  - Hamrah P
FAU - Gate, David
AU  - Gate D
FAU - Mott, Kevin R
AU  - Mott KR
FAU - Mantopoulos, Dimosthenis
AU  - Mantopoulos D
FAU - Zheng, Lixin
AU  - Zheng L
FAU - Town, Terrence
AU  - Town T
FAU - Jones, Clinton
AU  - Jones C
FAU - von Andrian, Ulrich H
AU  - von Andrian UH
FAU - Freeman, Gordon J
AU  - Freeman GJ
FAU - Sharpe, Arlene H
AU  - Sharpe AH
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
FAU - Ahmed, Rafi
AU  - Ahmed R
FAU - Wechsler, Steven L
AU  - Wechsler SL
FAU - Ghiasi, Homayon
AU  - Ghiasi H
LA  - eng
GR  - 1P20RR15635/RR/NCRR NIH HHS/United States
GR  - R01 EY013191/EY/NEI NIH HHS/United States
GR  - R01 EY013615/EY/NEI NIH HHS/United States
GR  - K08 EY020575-01/EY/NEI NIH HHS/United States
GR  - EY13615/EY/NEI NIH HHS/United States
GR  - EY13191/EY/NEI NIH HHS/United States
GR  - R01 AI069259/AI/NIAID NIH HHS/United States
GR  - P01 56299/PHS HHS/United States
GR  - K08 EY020575/EY/NEI NIH HHS/United States
GR  - P20 RR015635/RR/NCRR 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, Non-P.H.S.
DEP - 20110209
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CD8 Antigens)
RN  - 0 (Havcr2 protein, mouse)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (MicroRNAs)
RN  - 0 (Pdcd1 protein, mouse)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Receptors, Virus)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation/biosynthesis
MH  - CD8 Antigens/biosynthesis
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Flow Cytometry
MH  - Gene Expression Profiling
MH  - Hepatitis A Virus Cellular Receptor 2
MH  - Herpes Simplex/*immunology/virology
MH  - Herpesvirus 1, Human/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Programmed Cell Death 1 Receptor
MH  - Receptors, Virus/biosynthesis
MH  - Trigeminal Ganglion/*immunology
MH  - *Virus Latency
PMC - PMC3126262
EDAT- 2011/02/11 06:00
MHDA- 2011/06/15 06:00
PMCR- 2011/11/01
CRDT- 2011/02/11 06:00
PHST- 2011/02/11 06:00 [entrez]
PHST- 2011/02/11 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - JVI.02290-10 [pii]
AID - 2290-10 [pii]
AID - 10.1128/JVI.02290-10 [doi]
PST - ppublish
SO  - J Virol. 2011 May;85(9):4184-97. doi: 10.1128/JVI.02290-10. Epub 2011 Feb 9.