The HCMV membrane glycoprotein US10 selectively targets HLA-G for degradation
Name
Ploegh_The HCMV membrane.pdf
Size
3.71 MB
Format
Adobe PDF
Checksum (MD5)
e0529c9add031b542387a51306d08ffe
Author(s)
Park, Boyoun
Spooner, Eric
Houser, Brandy L.
Strominger, Jack L.
Ploegh, Hidde
Date Issued
August 2010
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press, The
Citation
Park, B., E. Spooner, B. L. Houser, J. L. Strominger, and H. L. Ploegh. “The HCMV membrane glycoprotein US10 selectively targets HLA-G for degradation.” Journal of Experimental Medicine 207, no. 9 (August 30, 2010): 2033-2041.
Version
Final published version
Abstract
Human cytomegalovirus (HCMV) encodes an endoplasmic reticulum (ER)-resident transmembrane glycoprotein, US10, expressed early in the replicative cycle of HCMV as part of the same cluster that encodes the known immunoevasins US2, US3, US6, and US11. We show that US10 down-regulates cell surface expression of HLA-G, but not that of classical class I MHC molecules. The unique and short cytoplasmic tail of HLA-G (RKKSSD) is essential in its role as a US10 substrate, and a tri-leucine motif in the cytoplasmic tail of US10 is responsible for down-regulation of HLA-G. Both the kinetics of HLA-G degradation and the mechanisms responsible appear to be distinct from those used by the US2 and US11 pathways, suggesting the existence of a third route of protein dislocation from the ER. We show that US10-mediated degradation of HLA-G interferes with HLA-G–mediated NK cell inhibition. Given the role of HLA-G in protecting the fetus from attack by the maternal immune system and in directing the differentiation of human dendritic cells to promote the evolution of regulatory T cells, HCMV likely targets the HLA-G–dependent axis of immune recognition no less efficiently than it interferes with classical class I MHC–restricted antigen presentation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1084/jem.20091793
