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Cell Rep. 2015 Feb 12. pii: S2211-1247(15)00054-6. doi: 10.1016/j.celrep.2015.01.029. [Epub ahead of print]

Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA∗008 to Escape Elimination by NK Cells.

Author information

1
The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
2
Institute for Virology of the University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
3
Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and the Chanock Center for Virology, IMRIC, Jerusalem 9112001, Israel.
4
The Institute for Drug Research, Hebrew University Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
5
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8886, USA.
6
Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Hermann-Herder Strasse 11, Freiburg 79104, Germany.
7
The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel. Electronic address: oferm@ekmd.huji.ac.il.

Abstract

Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host allele illustrates the dynamic co-evolution of host and pathogen.

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