Cytosolic Sensing of Viruses.

Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Immunity (Impact Factor: 19.75). 05/2013; 38(5):855-869. DOI: 10.1016/j.immuni.2013.05.007
Source: PubMed

ABSTRACT Cells are equipped with mechanisms that allow them to rapidly detect and respond to viruses. These defense mechanisms rely partly on receptors that monitor the cytosol for the presence of atypical nucleic acids associated with virus infection. RIG-I-like receptors detect RNA molecules that are absent from the uninfected host. DNA receptors alert the cell to the abnormal presence of that nucleic acid in the cytosol. Signaling by RNA and DNA receptors results in the induction of restriction factors that prevent virus replication and establish cell-intrinsic antiviral immunity. In light of these formidable obstacles, viruses have evolved mechanisms of evasion, masking nucleic acid structures recognized by the host, sequestering themselves away from the cytosol or targeting host sensors, and signaling adaptors for deactivation or degradation. Here, we detail recent advances in the molecular understanding of cytosolic nucleic acid detection and its evasion by viruses.

1 Follower
  • Source
    • "RLRs initiate signaling through IFNb-promoter stimulator-1 (IPS-1, also named Cardif, MAVS or VISA), leading to the activation of IFN regulatory factor (IRF) and nuclear factor-jB (NF-jB) pathways. Activation of the transcription factors IRF3, IRF7 and NF-jB is responsible for the transcription of genes coding for type I IFNs (IFNa and IFNb) and pro-inflammatory cytokines like IL-6 or TNFa, respectively [5]. These processes constitute the first steps of the innate response giving rise to an anti-viral defense within infected tissues, prior the intervention of the adaptive immune system. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Viral triggering of the innate immune response in infected cells aims at delaying viral replication and prevents tissue spreading. Viral replication is delayed by host protein synthesis inhibition and infected cell apoptosis on one hand, while infection spreading is controlled by the synthesis of specific proteins like type-I interferons (IFNs) and pro-inflammatory cytokines on the other hand. How do these two apparent conflicting responses cooperate within the same infected cells to mount effective defenses against pathogens? What are the molecules or the complexes resolving this contradiction over time? Some recent studies reveal unanticipated connections between innate immunity and stress pathways, giving important clues on how the cellular responses are orchestrated to limit infection efficiently. Copyright © 2015. Published by Elsevier B.V.
    FEBS letters 05/2015; 11. DOI:10.1016/j.febslet.2015.05.006 · 3.34 Impact Factor
  • Source
    • "Host innate immune system provides protection against virus attack by recognizing pathogen-associated molecular patterns (PAMPs) and generates both inflammatory and antiviral responses through pattern recognition receptors (PRRs) [1] [2]. PRRs are classified into several families. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nodamura virus (NoV) lethally infects suckling mice and contains a segmented positive-strand RNA genome that encodes a potent suppressor of RNA interference (RNAi). Recent studies have demonstrated immune detection and subsequent processing of NoV dsRNA replicative intermediates by the mouse RNAi machinery. However, diverse RNA viruses, including Encephalomyocarditis virus that also triggers Dicer-dependent biogenesis of viral siRNAs in mouse cells, are targeted in mammals by RIG-I-like receptors that initiate an IFN-dependent antiviral response. Using mouse embryonic fibroblasts (MEFs) for NoV infection, here we show that MEFs derived from mice knockout for RIG-I, but not those knockout for MDA5, LGP2, TLR3 or TLR7, exhibited an enhanced susceptibility to NoV. Further studies indicate that NoV infection induced an IFN-dependent antiviral response mediated by RIG-I. Our findings suggest that RIG-I directs a typical IFN-dependent antiviral response against an RNA virus capable of suppressing the RNAi response. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 04/2015; 460(4). DOI:10.1016/j.bbrc.2015.03.145 · 2.28 Impact Factor
  • Source
    • "Among these PRRs, TLRs and RLRs play important role in recognition of viruses or viral PAMPs [3] [4]. Upon activation by viral components, TLRs or RLRs transmit signals to the downstream adaptor molecules, which induce a large scale amplification of signaling cascade to activate interferons (IFNs) or nuclear factor-í µí¼…B (NF-í µí¼…B) pathways via IFN regulatory factors (IRFs) [5] [6]. Subsequently , IFN-I along with IFN-stimulated genes (ISGs) mediated the first antiviral defense [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Global fish production from aquaculture has rapidly grown over the past decades, and grass carp shares the largest portion. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in tremendous loss of grass carp (Ctenopharyngodon idella) industry. During the past years, development of molecular biology and cellular biology technologies has promoted significant advances in the understanding of the pathogen and the immune system. Immunoprophylaxis based on stimulation of the immune system of fish has also got some achievements. In this review, authors summarize the recent progresses in basic researches on GCRV; viral nucleic acid sensors, high-mobility group box proteins (HMGBs); pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and retinoic acid inducible gene I-(RIG-I-) like receptors (RLRs); antiviral immune responses induced by PRRs-mediated signaling cascades of type I interferon (IFN-I) and IFN-stimulated genes (ISGs) activation. The present review also notices the potential applications of molecule genetic markers. Additionally, authors discuss the current preventive and therapeutic strategies (vaccines, RNAi, and prevention medicine) and highlight the importance of innate immunity in long term control for grass carp hemorrhagic disease.
    Journal of Immunology Research 02/2015; 2015:Article ID 670437. DOI:10.1155/2015/670437 · 2.93 Impact Factor
Show more