Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis

• DOI: 10.1038/srep22550
• Publication Date: 2016-03-03T10:12:56Z
• Authors: Wei Wang; Wei-Hua Wang; Kazem M. Azadzoi; Ning Su; Peng Dai; Jianbin Sun; Qin Wang; Ping Liang; Wentao Zhang; Xiaoying Lei; Zhen Yan; Jing-Hua Yang
• Keywords: RNA Silencing

Abstract Viruses induce double-stranded RNA (dsRNA) in the host cells. The mammalian system has developed dsRNA-dependent recognition receptors such as RLRs that recognize long stretches of dsRNA PAMPs to activate interferon-mediated antiviral pathways and apoptosis severe infection. Here we report an efficient immune response through RLR receptor-mediated necroptosis against infections from different classes viruses. We demonstrated virus-infected A549 cells were efficiently killed presence a chimeric receptor, dsCARE. It measurably suppressed interferon pathway but promoted IL-1β production. Canonical cell death analysis by morphologic assessment, phosphatidylserine exposure, caspase cleavage chemical inhibition excluded involvement consistently suggested underlying mechanism infected death. necroptotic was augmented formation RIP1-RIP3 necrosome, recruitment MLKL protein activation cathepsin D. Contributing roles RIP1 RIP3 confirmed gene knockdown. Furthermore, inhibitor necrostatin-1 not pan-caspase zVAD impeded dsCARE-dependent Our data provides compelling evidence receptor shifts common responses leads rapid This could be targeted strategy.