PMID- 17977973
OWN - NLM
STAT- MEDLINE
DCOM- 20080124
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 2
DP  - 2008 Jan
TI  - Downregulation of the T-cell receptor complex and impairment of T-cell activation 
      by human herpesvirus 6 u24 protein.
PG  - 602-8
AB  - We have performed a screen aimed at identifying human herpesvirus 6 
      (HHV-6)-encoded proteins that modulate immune recognition. Here we show that the 
      U24 protein encoded by HHV-6 variant A downregulates cell surface expression of 
      the T-cell receptor (TCR)/CD3 complex, a complex essential to T-cell activation 
      and the generation of an immune adaptive response. In the presence of U24, the 
      TCR/CD3 complex is endocytosed but is not recycled back to the plasma membrane. 
      Instead, it accumulates in early and late endosomes. Interestingly, whereas CD3 
      downregulation from the cell surface is normally associated with T-cell 
      activation, U24 downregulates CD3 independently of T-cell activation. Moreover, 
      we found that U24-expressing T cells are resistant to activation by 
      antigen-presenting cells. HHV-6 has evolved a unique mechanism of inhibition of 
      T-cell activation that may impair the establishment of an adaptive immune 
      response. Furthermore, lymphocyte activation creates an environment favorable to 
      the reactivation and replication of lymphotropic herpesviruses. Thus, by 
      inhibiting T-cell activation, HHV-6 might limit its reactivation and thus 
      minimize immune recognition.
FAU - Sullivan, Brian M
AU  - Sullivan BM
AD  - Department of Molecular and Cell Biology, Division of Immunology, 142 LSA, 
      University of California, Berkeley, CA 94720-3200, USA.
FAU - Coscoy, Laurent
AU  - Coscoy L
LA  - eng
PT  - Journal Article
DEP - 20071031
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Antigen-Presenting Cells/immunology
MH  - Cell Membrane/chemistry
MH  - *Down-Regulation
MH  - Endoplasmic Reticulum/chemistry
MH  - Herpesvirus 6, Human/*immunology
MH  - Humans
MH  - *Lymphocyte Activation
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - T-Lymphocytes/*immunology
MH  - Viral Proteins/*immunology
PMC - PMC2224597
EDAT- 2007/11/06 09:00
MHDA- 2008/01/25 09:00
PMCR- 2008/05/01
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2008/01/25 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - JVI.01571-07 [pii]
AID - 1571-07 [pii]
AID - 10.1128/JVI.01571-07 [doi]
PST - ppublish
SO  - J Virol. 2008 Jan;82(2):602-8. doi: 10.1128/JVI.01571-07. Epub 2007 Oct 31.