Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense

PLoS Pathogens

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