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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.

SUBMITTER: Verma S

PROVIDER: S-EPMC4133390 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell-mediated antiviral defense.

Verma Shilpi S Loewendorf Andrea A Wang Qiao Q McDonald Bryan B Redwood Alec A Benedict Chris A CA

PLoS pathogens 20140814 8

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 expre ...[more]

PMID: 25122141

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