PMID- 21715478
OWN - NLM
STAT- MEDLINE
DCOM- 20111004
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 17
DP  - 2011 Sep
TI  - The herpes simplex virus 1 latency-associated transcript promotes functional 
      exhaustion of virus-specific CD8+ T cells in latently infected trigeminal 
      ganglia: a novel immune evasion mechanism.
PG  - 9127-38
LID - 10.1128/JVI.00587-11 [doi]
AB  - Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, 
      HSV-specific (HSV-gB(498-505) tetramer(+)) CD8(+) T cells are induced, 
      selectively retained in latently infected trigeminal ganglia (TG), and appear to 
      decrease HSV-1 reactivation. The HSV-1 latency-associated transcript (LAT) gene, 
      the only viral gene that is abundantly transcribed during latency, increases 
      reactivation. Previously we found that during latency with HSV-1 strain 
      McKrae-derived viruses, more of the total TG resident CD8 T cells expressed 
      markers of exhaustion with LAT(+) virus compared to LAT(-) virus. Here we extend 
      these findings to HSV-1 strain 17syn+-derived LAT(+) and LAT(-) viruses and to a 
      virus expressing just the first 20% of LAT. Thus, the previous findings were not 
      an artifact of HSV-1 strain McKrae, and the LAT function involved mapped to the 
      first 1.5 kb of LAT. Importantly, to our knowledge, we show here for the first 
      time that during LAT(+) virus latency, most of the HSV-1-specific TG resident CD8 
      T cells were functionally exhausted, as judged by low cytotoxic function and 
      decreased gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) 
      production. This resulted in LAT(-) TG having more functional HSV-gB(498-505) 
      tetramer(+) CD8(+) T cells compared to LAT(+) TG. In addition, LAT expression, in 
      the absence of other HSV-1 gene products, appeared to be able to directly or 
      indirectly upregulate both PD-L1 and major histocompatibility complex class I 
      (MHC-I) on mouse neuroblastoma cells (Neuro2A). These findings may constitute a 
      novel immune evasion mechanism whereby the HSV-1 LAT directly or indirectly 
      promotes functional exhaustion (i.e., dysfunction) of HSV-specific CD8(+) T cells 
      in latently infected TG, resulting in increased virus reactivation.
FAU - Chentoufi, Aziz A
AU  - Chentoufi AA
AD  - Laboratory of Cellular and Molecular Immunology, The Gavin Herbert Eye Institute, 
      University of California Irvine, School of Medicine, Irvine, California 92697, 
      USA.
FAU - Kritzer, Elizabeth
AU  - Kritzer E
FAU - Tran, Michael V
AU  - Tran MV
FAU - Dasgupta, Gargi
AU  - Dasgupta G
FAU - Lim, Chang Hyun
AU  - Lim CH
FAU - Yu, David C
AU  - Yu DC
FAU - Afifi, Rasha E
AU  - Afifi RE
FAU - Jiang, Xianzhi
AU  - Jiang X
FAU - Carpenter, Dale
AU  - Carpenter D
FAU - Osorio, Nelson
AU  - Osorio N
FAU - Hsiang, Chinhui
AU  - Hsiang C
FAU - Nesburn, Anthony B
AU  - Nesburn AB
FAU - Wechsler, Steven L
AU  - Wechsler SL
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
LA  - eng
GR  - R01 EY019896/EY/NEI NIH HHS/United States
GR  - R21 AI110902/AI/NIAID NIH HHS/United States
GR  - R03 EY014017/EY/NEI NIH HHS/United States
GR  - R01 EY014900/EY/NEI NIH HHS/United States
GR  - R01 EY024618/EY/NEI NIH HHS/United States
GR  - EY013191/EY/NEI NIH HHS/United States
GR  - EY14900/EY/NEI NIH HHS/United States
GR  - EY14017/EY/NEI NIH HHS/United States
GR  - R01 EY026103/EY/NEI NIH HHS/United States
GR  - R01 EY013191/EY/NEI NIH HHS/United States
GR  - EY019896/EY/NEI NIH HHS/United States
GR  - R01 EY018171/EY/NEI NIH HHS/United States
GR  - EY018171/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 - 20110629
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (MicroRNAs)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - Herpesvirus 1, Human/*immunology/*pathogenicity
MH  - *Immune Evasion
MH  - Interferon-gamma/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Trigeminal Ganglion/*virology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Virus Latency
PMC - PMC3165846
EDAT- 2011/07/01 06:00
MHDA- 2011/10/05 06:00
PMCR- 2012/03/01
CRDT- 2011/07/01 06:00
PHST- 2011/07/01 06:00 [entrez]
PHST- 2011/07/01 06:00 [pubmed]
PHST- 2011/10/05 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - JVI.00587-11 [pii]
AID - 0587-11 [pii]
AID - 10.1128/JVI.00587-11 [doi]
PST - ppublish
SO  - J Virol. 2011 Sep;85(17):9127-38. doi: 10.1128/JVI.00587-11. Epub 2011 Jun 29.