title: Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell-mediated antiviral defense.
abstract: 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.
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Verma
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Bryan
authors.initials: B
authors.lastname: McDonald
authors.affiliation: Microbiology and Immunology, School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Alec
authors.initials: A
authors.lastname: Redwood
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology / Q000378:metabolism; D041681:NIH 3T3 Cells; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D014764:Viral Proteins