PMID- 22512280
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20211021
IS  - 1557-8976 (Electronic)
IS  - 0882-8245 (Print)
IS  - 0882-8245 (Linking)
VI  - 25
IP  - 3
DP  - 2012 Jun
TI  - The herpes simplex virus type 1 latency-associated transcript inhibits phenotypic 
      and functional maturation of dendritic cells.
PG  - 204-15
LID - 10.1089/vim.2011.0091 [doi]
AB  - We recently found that the herpes simplex virus-1 (HSV-1) latency-associated 
      transcript (LAT) results in exhaustion of virus-specific CD8(+) T cells in 
      latently-infected trigeminal ganglia (TG). In this study we sought to determine 
      if this impairment may involve LAT directly and/or indirectly interfering with DC 
      maturation. We found that a small number of HSV-1 antigen-positive DCs are 
      present in the TG of latently-infected CD11c/eYFP mice; however, this does not 
      imply that these DCs are acutely or latently infected. Some CD8(+) T cells are 
      adjacent to DCs, suggesting possible interactions. It has previously been shown 
      that wild-type HSV-1 interferes with DC maturation. Here we show for the first 
      time that this is associated with LAT expression, since compared to LAT(-) virus: 
      (1) LAT(+) virus interfered with expression of MHC class I and the co-stimulatory 
      molecules CD80 and CD86 on the surface of DCs; (2) LAT(+) virus impaired DC 
      production of the proinflammatory cytokines IL-6, IL-12, and TNF-alpha; and (3) DCs 
      infected in vitro with LAT(+) virus had significantly reduced the ability to 
      stimulate HSV-specific CD8(+) T cells. While a similar number of DCs was found in 
      LAT(+) and LAT(-) latently-infected TG of CD11c/eYFP transgenic mice, more HSV-1 
      Ag-positive DCs and more exhausted CD8 T cells were seen with LAT(+) virus. 
      Consistent with these findings, HSV-specific cytotoxic CD8(+) T cells in the TG of 
      mice latently-infected with LAT(+) virus produced less IFN-gamma and TNF-alpha than those 
      from TG of LAT(-)-infected mice. Together, these results suggest a novel 
      immune-evasion mechanism whereby the HSV-1 LAT increases the number of HSV-1 
      Ag-positive DCs in latently-infected TG, and interferes with DC phenotypic and 
      functional maturation. The effect of LAT on TG-resident DCs may contribute to the 
      reduced function of HSV-specific CD8(+) T cells in the TG of mice latently infected 
      with LAT(+) virus.
FAU - Chentoufi, Aziz Alami
AU  - Chentoufi AA
AD  - Laboratory of Cellular and Molecular Immunology, School of Medicine, University 
      of California-Irvine, Irvine, California, USA.
FAU - Dervillez, Xavier
AU  - Dervillez X
FAU - Dasgupta, Gargi
AU  - Dasgupta G
FAU - Nguyen, Chelsea
AU  - Nguyen C
FAU - Kabbara, Khaled W
AU  - Kabbara KW
FAU - Jiang, Xianzhi
AU  - Jiang X
FAU - Nesburn, Anthony B
AU  - Nesburn AB
FAU - Wechsler, Steven L
AU  - Wechsler SL
FAU - Benmohamed, Lbachir
AU  - Benmohamed L
LA  - eng
GR  - EY14017/EY/NEI NIH HHS/United States
GR  - EY019896/EY/NEI NIH HHS/United States
GR  - EY018171/EY/NEI NIH HHS/United States
GR  - R01 EY019896/EY/NEI NIH HHS/United States
GR  - R01 EY014900/EY/NEI NIH HHS/United States
GR  - EY013191/EY/NEI NIH HHS/United States
GR  - EY14900/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 - 20120418
PL  - United States
TA  - Viral Immunol
JT  - Viral immunology
JID - 8801552
RN  - 0 (MicroRNAs)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/immunology/virology
MH  - Cell Differentiation/*drug effects
MH  - Dendritic Cells/cytology/*drug effects
MH  - Herpes Simplex/*immunology/virology
MH  - Herpesvirus 1, Human/*physiology
MH  - *Immune Evasion
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/immunology/*physiology
MH  - Phenotype
MH  - Trigeminal Ganglion/immunology/virology
MH  - Virus Latency/immunology
PMC - PMC3366336
EDAT- 2012/04/20 06:00
MHDA- 2012/10/12 06:00
PMCR- 2012/06/01
CRDT- 2012/04/20 06:00
PHST- 2012/04/20 06:00 [entrez]
PHST- 2012/04/20 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - 10.1089/vim.2011.0091 [pii]
AID - 10.1089/vim.2011.0091 [doi]
PST - ppublish
SO  - Viral Immunol. 2012 Jun;25(3):204-15. doi: 10.1089/vim.2011.0091. Epub 2012 Apr 
      18.