title: Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA∗008 to Escape Elimination by NK Cells.
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, MICA∗008, 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 MICA∗008 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.
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Einat
authors: E
authors: Seidel
authors: Institute for Virology of the University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
authors: Vu Thuy Khanh
authors: VTK
authors: Le
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Yotam
authors: Y
authors: Bar-On
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Pinchas
authors: P
authors: Tsukerman
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Jonatan
authors: J
authors: Enk
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Rachel
authors: R
authors: Yamin
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Natan
authors: N
authors: Stein
authors: The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
authors: Dominik
authors: D
authors: Schmiedel
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and the Chanock Center for Virology, IMRIC, Jerusalem 9112001, Israel.
authors: Esther
authors: E
authors: Oiknine Djian
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and the Chanock Center for Virology, IMRIC, Jerusalem 9112001, Israel.
authors: Yiska
authors: Y
authors: Weisblum
authors: The Institute for Drug Research, Hebrew University Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
authors: Boaz
authors: B
authors: Tirosh
authors: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8886, USA.
authors: Peter
authors: P
authors: Stastny
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center and Department of Biochemistry and the Chanock Center for Virology, IMRIC, Jerusalem 9112001, Israel.
authors: Dana G
authors: DG
authors: Wolf
authors: Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Hermann-Herder Strasse 11, Freiburg 79104, Germany.
authors: Hartmut
authors: H
authors: Hengel
authors: 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.
authors: Ofer
authors: O
authors: Mandelboim