Inhibition of the TRAIL death receptor by CMV reveals its importance in NK Cell-Mediated antiviral defense

Verma, S., Loewendorf, A., Wang, Q., McDonald, B., Redwood, A. and Benedict, C.A. (2014) Inhibition of the TRAIL death receptor by CMV reveals its importance in NK Cell-Mediated antiviral defense. PLoS Pathogens, 10 (8). e1004268.

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.

Item Type:	Journal Article
Publisher:	Public Library of Science
Copyright:	© 2014 Verma et al.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/30868

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