Inhibition of natural killer cell-mediated cytotoxicity by Kaposi's sarcoma-associated herpesvirus K5 protein.
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.
Ishido
S
S
Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Choi
J K
JK
Lee
B S
BS
Wang
C
C
DeMaria
M
M
Johnson
R P
RP
Cohen
G B
GB
Jung
J U
JU
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D051940:B7-2 Antigen; D002462:Cell Membrane / Q000276:immunology / Q000821:virology; D003593:Cytoplasm / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D004357:Drug Synergism; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000502:physiology*; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000821:virology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D017874:Immediate-Early Proteins; D007166:Immunosuppressive Agents; C405867:K5 protein, Human herpesvirus 8; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1