Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112
Open Access
- 1 August 2010
- journal article
- Published by Microbiology Society in Journal of General Virology
- Vol. 91 (8), 2034-2039
- https://doi.org/10.1099/vir.0.021931-0
Abstract
Human cytomegalovirus (HCMV) UL141 induces protection against natural killer cell-mediated cytolysis by downregulating cell surface expression of CD155 (nectin-like molecule 5; poliovirus receptor), a ligand for the activating receptor DNAM-1 (CD226). However, DNAM-1 is also recognized to bind a second ligand, CD112 (nectin-2). We now show that HCMV targets CD112 for proteasome-mediated degradation by 48 h post-infection, thus removing both activating ligands for DNAM-1 from the cell surface during productive infection. Significantly, cell surface expression of both CD112 and CD155 was restored when UL141 was deleted from the HCMV genome. While gpUL141 alone is sufficient to mediate retention of CD155 in the endoplasmic reticulum, UL141 requires assistance from additional HCMV-encoded functions to suppress expression of CD112.Keywords
This publication has 47 references indexed in Scilit:
- Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motilityProceedings of the National Academy of Sciences of the United States of America, 2009
- Up on the tightrope: natural killer cell activation and inhibitionNature Immunology, 2008
- Modulation of natural killer cells by human cytomegalovirusJournal of Clinical Virology, 2008
- Cytomegalovirus Destruction of Focal Adhesions Revealed in a High-Throughput Western Blot Analysis of Cellular Protein ExpressionJournal of Virology, 2007
- Downregulation of natural killer cell–activating ligand CD155 by human cytomegalovirus UL141Nature Immunology, 2005
- DNAM-1 and PVR Regulate Monocyte Migration through Endothelial JunctionsThe Journal of Experimental Medicine, 2004
- CD226 Mediates Platelet and Megakaryocytic Cell Adhesion to Vascular Endothelial CellsJournal of Biological Chemistry, 2003
- Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICAScience, 1999
- The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the CytosolCell, 1996
- Severe Herpesvirus Infections in an Adolescent without Natural Killer CellsThe New England Journal of Medicine, 1989