Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) K3 and K5 proteins dramatically downregulate MHC class I molecules. However, although MHC class I downregulation may protect KSHV-infected cells from cytotoxic T lymphocyte recognition, these cells become potential targets for natural killer (NK) cell-mediated lysis. We now show that K5 also downregulates ICAM-1 and B7-2, which are ligands for NK cell-mediated cytotoxicity receptors. As a consequence, K5 expression drastically inhibits NK cell-mediated cytotoxicity. Conversely, de novo expression of B7-2 and ICAM-1 resensitizes the K5-expressing cells to NK cell-mediated cytotoxicity. This is a novel viral immune evasion strategy where KSHV K5 achieves immune avoidance by downregulation of cellular ligands for NK cell-mediated cytotoxicity receptors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / physiology
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B7-2 Antigen
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Cell Membrane / immunology
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Cell Membrane / virology
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Cytoplasm / immunology
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Cytoplasm / virology
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Cytotoxicity, Immunologic / immunology*
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Down-Regulation / immunology
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Drug Synergism
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Herpesvirus 8, Human / immunology*
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Humans
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Immediate-Early Proteins / biosynthesis
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Immediate-Early Proteins / physiology*
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Immunity, Innate
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Immunosuppressive Agents / pharmacology*
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Intercellular Adhesion Molecule-1 / biosynthesis
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Intercellular Adhesion Molecule-1 / physiology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / virology
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Lymphocyte Activation / immunology
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / physiology
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Tumor Cells, Cultured / immunology
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / virology
Substances
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Antigens, CD
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B7-2 Antigen
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CD86 protein, human
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Immediate-Early Proteins
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Immunosuppressive Agents
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K5 protein, Human herpesvirus 8
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Membrane Glycoproteins
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Intercellular Adhesion Molecule-1