Synthetic Abortive HIV-1 RNAs Induce Potent Antiviral Immunity.

FRONTIERS IN IMMUNOLOGY(2020)

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摘要
Strong innate and adaptive immune responses are paramount in combating viral infections. Dendritic cells (DCs) detect viral infections via cytosolic RIG-I like receptors (RLRs) RIG-I and MDA5 leading to MAVS-induced immunity. The DEAD-box RNA helicase DDX3 senses abortive human immunodeficiency virus 1 (HIV-1) transcripts and induces MAVS-dependent type I interferon (IFN) responses, suggesting that abortive HIV-1 RNA transcripts induce antiviral immunity. Little is known about the induction of antiviral immunity by DDX3-ligand abortive HIV-1 RNA. Here we synthesized a 58 nucleotide-long capped RNA (HIV-1 Cap-RNA(58)) that mimics abortive HIV-1 RNA transcripts. HIV-1 Cap-RNA(58) induced potent type I IFN responses in monocyte-derived DCs, monocytes, macrophages and primary CD1c(+) DCs. Compared with RLR agonist poly-I:C, HIV-1 Cap-RNA(58) induced comparable levels of type I IFN responses, identifying HIV-1 Cap-RNA(58) as a potent trigger of antiviral immunity. In monocyte-derived DCs, HIV-1 Cap-RNA(58) activated the transcription factors IRF3 and NF-kappa B. Moreover, HIV-1 Cap-RNA(58) induced DC maturation and the expression of pro-inflammatory cytokines. HIV-1 Cap-RNA(58)-stimulated DCs induced proliferation of CD4(+) and CD8(+) T cells and differentiated naive T helper (T-H) cells toward a T(H)2 phenotype. Importantly, treatment of DCs with HIV-1 Cap-RNA(58) resulted in an efficient antiviral innate immune response that reduced ongoing HIV-1 replication in DCs. Our data strongly suggest that HIV-1 Cap-RNA(58) induces potent innate and adaptive immune responses, making it an interesting addition in vaccine design strategies.
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关键词
abortive HIV-1 RNA,type I IFN,viral sensing,DDX3,pattern recognition receptor,dendritic cells,antiviral immunity
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