PLoS Pathogens | |
Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense | |
Shilpi Verma1  Chris A. Benedict1  Bryan McDonald1  Qiao Wang1  Andrea Loewendorf1  Alec Redwood2  | |
[1] Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America;Microbiology and Immunology, School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia | |
关键词: NK cells; Viral replication; NIH 3T3 cells; Spleen; Apoptosis; Cytokines; Cytomegalovirus infection; Human cytomegalovirus; | |
DOI : 10.1371/journal.ppat.1004268 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF-family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR−/− mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses.
【 授权许可】
CC BY
【 预 览 】
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RO201902018306156ZK.pdf | 2872KB | download |