Discriminating self from non-self in nucleic acid sensing

Abstract

Innate immunity against pathogens relies on an array of immune receptors to detect molecular patterns that are characteristic of the pathogens, including receptors that are specialized in the detection of foreign nucleic acids. In vertebrates, nucleic acid sensing is the dominant antiviral defence pathway. Stimulation of nucleic acid receptors results in antiviral immune responses with the production of type I interferon (IFN), as well as the expression of IFN-stimulated genes, which encode molecules such as cell-autonomous antiviral effector proteins. This Review summarizes the tremendous progress that has been made in understanding how this sophisticated immune sensory system discriminates self from non-self nucleic acids in order to reliably detect pathogenic viruses.

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

“…As shown above, RIG‐I, which recognizes relatively short (< 300 bp) cytoplasmic dsRNA (Schlee & Hartmann, 2016), serves as the main mediator of the interferon response upon HNRNPC KD, while MDA5, which senses longer dsRNA (DeWitte‐Orr & Mossman, 2010; Wu et al , 2013; Reikine et al , 2014), was not involved (Fig 5). Therefore, we are interested in the pool of short (< 500 bp) dsRNA species and developed a strategy to pull down the short dsRNA with the anti‐dsRNA J2 antibody from the total RNA.…”

Double-stranded RNA innate immune response activation from long-term adeno-associated virus vector transduction

“…In addition to the transmembrane TLRs, cytoplasmic PRRs can also detect viral nucleic acids or proteins from viral infection. Generally, RIG-I and MDA5 are able to sense cytosolic dsRNA from RNA viruses, and several DNA sensors in cytoplasm have been identified (24). NLR proteins are also involved in the innate immune response to virus infection (32).…”

“…MDA5 and RIG-I share high sequence similarity and a common signaling adaptor, mitochondrial antiviral signaling (MAVS), but they play nonredundant functions in antiviral immunity by recognizing different viruses or viral RNA (23,24). RIG-I recognizes 5′-triphosphorylated blunt-ended, short dsRNA or ss RNA hairpins that are often present in a variety of positive-and negative-strand viruses (25)(26)(27).…”

The RIG‐I‐like receptor LGP2 inhibits Dicer‐dependent processing of long double‐stranded RNA and blocks RNA interference in mammalian cells

“…In mammals, the type I interferon (IFN) response constitutes an effective means to halt viral intruders. This innate immune response is initiated by the recognition of virally derived nucleic acids within the host cells by a dedicated group of receptors, which signal to induce a transcriptional response resulting in the production and secretion of type I IFNs (mainly IFN‐α and IFN‐β; Goubau et al , 2013; Schneider et al , 2014; Wu & Chen, 2014; Schlee & Hartmann, 2016). These key antiviral cytokines signal in an autocrine and paracrine fashion via the type I interferon receptor (IFNAR) to induce the expression of hundreds of interferon‐stimulated genes (ISGs) that encode proteins that inhibit viral replication and dissemination (Goubau et al , 2013; Schneider et al , 2014).…”

“…This family of DExH/D helicases encompasses RIG‐I (retinoic acid‐inducible gene I), MDA5 (melanoma differentiation‐associated gene 5) and LGP2 (laboratory of genetics and physiology 2; Goubau et al , 2013; Wu & Chen, 2014; Schlee & Hartmann, 2016). RIG‐I and MDA5 share a similar domain organisation.…”