PMID- 19332782
OWN - NLM
STAT- MEDLINE
DCOM- 20090512
LR  - 20220330
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 15
DP  - 2009 Apr 14
TI  - Unconventional ligand activation of herpesvirus entry mediator signals cell 
      survival.
PG  - 6244-9
LID - 10.1073/pnas.0902115106 [doi]
AB  - The herpesvirus entry mediator (HVEM; TNFRSF14) activates NF-kappaB through the 
      canonical TNF-related cytokine LIGHT, serving as a costimulatory pathway during 
      activation of T cells. HVEM also functions as a ligand for the Ig superfamily 
      members B and T lymphocyte attenuator (BTLA) and CD160, both of which limit 
      inflammatory responses initiated by T cells. Emerging evidence indicates BTLA 
      also promotes T cell survival, but its structural differences from LIGHT intimate 
      BTLA is unlikely to function as an activator of HVEM. We demonstrate here that 
      BTLA, CD160, and herpes simplex virus envelope glycoprotein D (gD) function as 
      activating ligands for HVEM, promoting NF-kappaB activation and cell survival. 
      Membrane-expressed BTLA and CD160, as well as soluble dimeric receptor surrogates 
      BTLA-Fc and gD-Fc specifically activated HVEM-dependent NF-kappaB. BTLA and CD160 
      engagement induced recruitment of TNF receptor-associated factor 2 (TRAF2), but 
      not TRAF3, to HVEM that specifically activated the RelA but not the RelB form of 
      NF-kappaB in a mucosal epithelial tumor cell line. Moreover, Btla(-/-) T cells 
      survived poorly following activation but were rescued with BTLA-Fc, indicating 
      HVEM-BTLA bidirectional signaling may serve as a critical cell-survival system 
      for lymphoid and epithelial cells.
FAU - Cheung, Timothy C
AU  - Cheung TC
AD  - Divisions of Molecular Immunology and Developmental Immunology, La Jolla 
      Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, 
      USA.
FAU - Steinberg, Marcos W
AU  - Steinberg MW
FAU - Oborne, Lisa M
AU  - Oborne LM
FAU - Macauley, Matthew G
AU  - Macauley MG
FAU - Fukuyama, Satoshi
AU  - Fukuyama S
FAU - Sanjo, Hideki
AU  - Sanjo H
FAU - D'Souza, Claire
AU  - D'Souza C
FAU - Norris, Paula S
AU  - Norris PS
FAU - Pfeffer, Klaus
AU  - Pfeffer K
FAU - Murphy, Kenneth M
AU  - Murphy KM
FAU - Kronenberg, Mitchell
AU  - Kronenberg M
FAU - Spear, Patricia G
AU  - Spear PG
FAU - Ware, Carl F
AU  - Ware CF
LA  - eng
GR  - AI067890/AI/NIAID NIH HHS/United States
GR  - R24 DK080506/DK/NIDDK NIH HHS/United States
GR  - DK 080506/DK/NIDDK NIH HHS/United States
GR  - R37AI33068/AI/NIAID NIH HHS/United States
GR  - R37AI036293/AI/NIAID NIH HHS/United States
GR  - R01 AI061516/AI/NIAID NIH HHS/United States
GR  - CA069381/CA/NCI NIH HHS/United States
GR  - R37 AI033068/AI/NIAID NIH HHS/United States
GR  - U19 AI031494/AI/NIAID NIH HHS/United States
GR  - AI48073/AI/NIAID NIH HHS/United States
GR  - P01 CA069381/CA/NCI NIH HHS/United States
GR  - AI61516/AI/NIAID NIH HHS/United States
GR  - R01 AI067890/AI/NIAID NIH HHS/United States
GR  - R37 AI036293/AI/NIAID NIH HHS/United States
GR  - R01 AI048073/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090330
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 0 (BTLA protein, human)
RN  - 0 (CD160 protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Immunoglobulins)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 14)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16535-6
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Cell Line
MH  - Cell Survival/immunology
MH  - GPI-Linked Proteins
MH  - Humans
MH  - Immunoglobulins/immunology
MH  - Ligands
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Receptors, Immunologic/immunology
MH  - Receptors, Tumor Necrosis Factor, Member 14/*immunology
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/cytology/immunology
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Viral Envelope Proteins/immunology
PMC - PMC2669392
COIS- The authors declare no conflict of interest.
EDAT- 2009/04/01 09:00
MHDA- 2009/05/13 09:00
PMCR- 2009/10/14
CRDT- 2009/04/01 09:00
PHST- 2009/04/01 09:00 [entrez]
PHST- 2009/04/01 09:00 [pubmed]
PHST- 2009/05/13 09:00 [medline]
PHST- 2009/10/14 00:00 [pmc-release]
AID - 0902115106 [pii]
AID - 7587 [pii]
AID - 10.1073/pnas.0902115106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6244-9. doi: 
      10.1073/pnas.0902115106. Epub 2009 Mar 30.