Abstract
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-RNA58) that mimics abortive HIV-1 RNA transcripts. HIV-1 Cap-RNA58 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-RNA58 induced comparable levels of type I IFN responses, identifying HIV-1 Cap-RNA58 as a potent trigger of antiviral immunity. In monocyte-derived DCs, HIV-1 Cap-RNA58 activated the transcription factors IRF3 and NF-κB. Moreover, HIV-1 Cap-RNA58 induced DC maturation and the expression of pro-inflammatory cytokines. HIV-1 Cap-RNA58-stimulated DCs induced proliferation of CD4+ and CD8+ T cells and differentiated naïve T helper (TH) cells toward a TH2 phenotype. Importantly, treatment of DCs with HIV-1 Cap-RNA58 resulted in an efficient antiviral innate immune response that reduced ongoing HIV-1 replication in DCs. Our data strongly suggest that HIV-1 Cap-RNA58 induces potent innate and adaptive immune responses, making it an interesting addition in vaccine design strategies.
Highlights
Evoking potent and tailored antiviral responses by the host is paramount in combating viral infections [1]
We investigated whether human immunodeficiency virus 1 (HIV-1) Cap-RNA58 induced type I IFN responses in monocyte-derived Dendritic cells (DCs) (DCs) by treating DCs with HIV-1 Cap-RNA58 complexed with transfection reagent lyovec to facilitate cytoplasmic delivery [27]
RNA helicase DDX3 is important for the transport of HIV1 Tat mRNA as well as the formation of translation initiation complexes required for HIV-1 translation [30,31,32]
Summary
Evoking potent and tailored antiviral responses by the host is paramount in combating viral infections [1]. Dendritic cells (DCs) induce antiviral immune responses by recognizing invading viruses via pattern recognition receptors (PRRs). PRR triggering by viral pathogen-associated molecular patterns (PAMPs) induces DC maturation and activation as well as differentiation of naïve T cells [2,3,4]. Certain PRRs such as the RIG-I-like receptors (RLRs) induce strong antiviral innate immune responses initiated by expression of type I interferon (IFN) responses. RIG-I (DDX58) and MDA5 are two well-described RLRs and important in antiviral immunity to e.g., Influenza viruses, Dengue virus, and West Nile virus [7,8,9].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
