Intracellular detection of viral nucleic acids

Sparrer, Konstantin M. J.; Gack, Michaela U.

doi:10.1016/j.mib.2015.03.001

Cited by 99 publications

(93 citation statements)

References 85 publications

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“…In the last number of years, the cytoplasmic DExD/H box helicase family members, RIG-I and MDA5, have been shown to be critical determinants of the development of the innate immune response against numerous RNA viruses (Brubaker et al, 2015; Sparrer and Gack, 2015; Weber and Weber, 2014; Wilkins and Gale, 2010). These proteins, termed RIG-I-like receptors, are the primary sensors of virus-specific dsRNA ligands, and their activation initiates signaling cascades through the MAVS adaptor, which ultimately induce type I IFN expression.…”

Section: Resultsmentioning

confidence: 99%

Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

2016

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Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5.

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Section: Resultsmentioning

confidence: 99%

Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

2016

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“…Such structures include peptidoglycans, zymosan, lipopolysaccharides, flagellin, double-stranded and single-stranded RNA, and CpG-containing DNA (1). So far, an ever-increasing number of receptors with the capacity to sense and respond to these PAMPs have been identified and are broadly categorized into distinct receptor families: Toll-like receptors (TLR), RIG-1 (retinoic acid-inducible gene I)-like receptors (RLR), NOD-like receptors, and C-type lectin receptors (2–4). Following engagement, these pattern-recognition receptors trigger the activation of several inflammatory pathways essential to mediate robust anti-microbial activity and induce sustained immune responses.…”

mentioning

confidence: 99%

The Role and Function of Fcγ Receptors on Myeloid Cells

2016

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A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes. By directly linking the innate and the adaptive components of immunity, Fc receptors play a central role in host defense and the maintenance of tissue homeostasis through the induction of diverse proinflammatory, anti-inflammatory, and immunomodulatory processes that are initiated upon engagement by the Fc domain. In this chapter, we discuss the mechanisms that regulate Fc domain binding to the various types of Fc receptors and provide an overview of the astonishing diversity of effector functions that are mediated through Fc-FcR interactions on myeloid cells. Lastly, we discuss the impact of FcR-mediated interactions in the context of IgG-mediated inflammation, autoimmunity, susceptibility to infection, and responsiveness to antibody-based therapeutics.

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“…In animals, Toll-interleukin 1-like receptors (TLRs), which are structurally similar to plant RLKs and NB-LRRs, perceive viral RNA and DNA in endosomes and on cell membranes (55). In addition, RIG-I and MDA5 for viral RNA and IFI16 and cGAS for viral DNA have been identified as receptors that perceive PAMPs in the cytoplasm and nucleus (56). A NOD-like receptor and other host factors have been implicated in recognition of viral infection (56).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, RIG-I and MDA5 for viral RNA and IFI16 and cGAS for viral DNA have been identified as receptors that perceive PAMPs in the cytoplasm and nucleus (56). A NOD-like receptor and other host factors have been implicated in recognition of viral infection (56). However, no CaM or CaM-like protein (CML) has previously been identified to be an immune receptor.…”

Section: Discussionmentioning

confidence: 99%

rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming

Jeon

Tadamura

Murakami

et al. 2017

J Virol

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Primary infection of a plant with a pathogen that causes high accumulation of salicylic acid in the plant typically via a hypersensitive response confers enhanced resistance against secondary infection with a broad spectrum of pathogens, including viruses. This phenomenon is called systemic acquired resistance (SAR), which is a plant priming for adaption to repeated biotic stress. However, the molecular mechanisms of SAR-mediated enhanced inhibition, especially of virus infection, remain unclear. Here, we show that SAR against cucumber mosaic virus (CMV) in tobacco plants (Nicotiana tabacum) involves a calmodulin-like protein, rgs-CaM. We previously reported the antiviral function of rgs-CaM, which binds to and directs degradation of viral RNA silencing suppressors (RSSs), including CMV 2b, via autophagy. We found that rgs-CaM-mediated immunity is ineffective against CMV infection in normally growing tobacco plants but is activated as a result of SAR induction via salicylic acid signaling. We then analyzed the effect of overexpression of rgsCaM on salicylic acid signaling. Overexpressed and ectopically expressed rgs-CaM induced defense reactions, including cell death, generation of reactive oxygen species, and salicylic acid signaling. Further analysis using a combination of the salicylic acid analogue benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and the Ca 2ϩ ionophore A23187 revealed that rgs-CaM functions as an immune receptor that induces salicylic acid signaling by simultaneously perceiving both viral RSS and Ca 2ϩ influx as infection cues, implying its autoactivation. Thus, secondary infection of SAR-induced tobacco plants with CMV seems to be effectively inhibited through 2b recognition and degradation by rgs-CaM, leading to reinforcement of antiviral RNA silencing and other salicylic acid-mediated antiviral responses.IMPORTANCE Even without an acquired immune system like that in vertebrates, plants show enhanced whole-plant resistance against secondary infection with pathogens; this so-called systemic acquired resistance (SAR) has been known for more than half a century and continues to be extensively studied. SAR-induced plants strongly and rapidly express a number of antibiotics and pathogenesis-related proteins targeted against secondary infection, which can account for enhanced resistance against bacterial and fungal pathogens but are not thought to control viral infection. This study showed that enhanced resistance against cucumber mosaic virus is caused by a tobacco calmodulin-like protein, rgs-CaM, which detects and counteracts the major viral virulence factor (RNA silencing suppressor) after SAR induction. rgs-CaM-mediated SAR illustrates the growth versus defense trade-off in plants, as it targets the major virulence factor only under specific biotic stress conditions, thus avoiding the cost of constitutive activation while reducing the damage from virus infection.

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Intracellular detection of viral nucleic acids

Cited by 99 publications

References 85 publications

Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

The Role and Function of Fcγ Receptors on Myeloid Cells

rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming

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