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PMID: 15864354 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of CD1d expression and function by a herpesvirus infection.

The Journal of clinical investigation ·Vol. 115 ·No. 5 ·2005-05-00 ·Pages 1369-78

Sanchez DJ, Gumperz JE, Ganem D

Abstract

Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that the lytic replication cycle of the Kaposi sarcoma-associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This is caused by expression of the 2 modulator of immune recognition (MIR) proteins of the virus, each of which promotes the loss of surface CD1d expression following transfection into uninfected cells. Inhibition of CD1d surface expression is due to ubiquitination of the CD1d alpha-chain on a unique lysine residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated MHC class I downregulation, however, CD1d downregulation does not appear to include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d results in reduced activation of CD1d-restricted T cells in vitro. KSHV modulation of CD1d expression represents a strategy for viral evasion of innate host immune responses and implicates CD1d-restricted T cells as regulators of this viral infection.

MeSH Terms
Antigens, CD1/biosynthesis,genetics,immunology Antigens, CD1d Down-Regulation/physiology Herpesviridae Infections/immunology,metabolism Herpesvirus 8, Human/immunology,metabolism Humans Ubiquitin/metabolism Viral Proteins/metabolism Virus Replication/physiology
Chemicals
Antigens, CD1 Antigens, CD1d CD1D protein, human MIR1 protein, human herpesvirus 8 MIR2 protein, human herpesvirus 8 Ubiquitin Viral Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sanchez David Jesse
George Williams Hooper Foundation, University of California, San Francisco, 94143, USA.
Gumperz Jenny E
Ganem Don
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI24041
Published
2005-05-00
Pages
1369-78
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1087176
Subset
IM
Grants
NHLBI NIH HHS · R01 HL071590 · United States
NIGMS NIH HHS · R25 GM056847 · United States
NIGMS NIH HHS · 1R25GM56847 · United States
Corrections
CommentIn
PMID: 15864346
External Links
PubMed source DOI: 10.1172/JCI24041 PMC Full Text View journal details
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