The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B.

Abstract	The Us3 kinase is part of the antiapoptotic arsenal that salvages herpes simplex virus (HSV)-1-infected cells from damage caused by different stimuli. We demonstrate that Us3 protects HSV-1-infected cells from lysis by MHC class I-restricted CD8T cells without affecting antigen presentation. Expression of Us3 was associated with inhibition of caspase activation and reduced cleavage of the proapoptotic protein Bid. Recombinant granzyme B (GrB) failed to cleave Bid in cytosolic extracts from Us3 positive cells, while recombinant Bid served as substrate for Us3 phosphorylation, suggesting that modification of Bid by Us3 blocks its processing by GrB. Our data illustrate a new strategy of viral escape, where modification of a cellular proapoptotic substrate may prevent lysis of the infected cells without affecting other T-cell functions.
Authors	A Cartier, E Broberg, T Komai, M Henriksson, M G Masucci
Journal	Cell death and differentiation (Cell Death Differ) Vol. 10 Issue 12 Pg. 1320-8 (Dec 2003) ISSN: 1350-9047 [Print] England
PMID	12934063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BH3 Interacting Domain Death Agonist Protein BID protein, human Carrier Proteins Recombinant Proteins Tumor Necrosis Factor-alpha Viral Proteins Protein Serine-Threonine Kinases US3 protein, Human herpesvirus 1 GZMB protein, human Granzymes Serine Endopeptidases Caspases
Topics	Antigen Presentation Apoptosis BH3 Interacting Domain Death Agonist Protein Blotting, Western CD8-Positive T-Lymphocytes (metabolism) Carrier Proteins (metabolism) Caspases (metabolism) Cell Line Cytosol (metabolism) Dose-Response Relationship, Drug Enzyme Activation Granzymes Humans Lymphocytes (metabolism) Major Histocompatibility Complex Microscopy, Fluorescence Mutation Phosphorylation Protein Binding Protein Serine-Threonine Kinases (metabolism, physiology) Recombinant Proteins (chemistry, metabolism) Serine Endopeptidases (pharmacology) T-Lymphocytes, Cytotoxic (metabolism) Tumor Necrosis Factor-alpha (metabolism) Viral Proteins

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