[PDF][PDF] Inhibition of natural killer cell–mediated cytotoxicity by Kaposi's sarcoma–associated herpesvirus K5 protein

S Ishido, JK Choi, BS Lee, C Wang, M DeMaria… - Immunity, 2000 - cell.com
S Ishido, JK Choi, BS Lee, C Wang, M DeMaria, RP Johnson, GB Cohen, JU Jung
Immunity, 2000cell.com
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 …
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.
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