Comparative analysis of viral RNA signatures on different RIG-I-like receptors

David, Raul Y. Sanchez; Combredet, Chantal; Sismeiro, Odile; Dillies, Marie‐Agnès; Jagla, Bernd; Coppée, Jean‐Yves; Mura, Marie; Galla, Mathilde Guerbois; Desprès, Philippe; Tangy, Frédéric; Komarova, Anastassia V.

doi:10.7554/elife.11275

Cited by 84 publications

(115 citation statements)

References 76 publications

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“…It can recognize a panel of viruses, including vesicular stomatitis virus, Sendai virus, influenza virus, Ebola virus, and EBV, etc. [37][38][39] . It has been demonstrated that short dsRNAs with a triphosphate-or diphosphate-motif at the 5 ′ end are major ligands for RIG-I.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Lu¹,

Qin²,

Jia³

et al. 2017

J Innate Immun

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Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance.

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Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Lu¹,

Qin²,

Jia³

et al. 2017

J Innate Immun

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show abstract

“…The dynamic nature of host-pathogen molecular interactions may result in potentially radical changes over time in the specific pathogen-associated molecules recognized by host immune receptors. Viral RNA sequences can change extremely rapidly, and although structural analyses and early functional studies have suggested that RLR-RNA interactions are not strongly affected by sequence variation [52, 84], changes in viral RNA sequences might impact RLR immune signaling under some circumstances [105–107]. Many viruses biochemically ‘hide’ their RNAs to avoid host detection [108–110], and viruses are known to antagonize various aspects of the RLR system [111–113].…”

Section: Discussionmentioning

confidence: 99%

Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference

et al. 2016

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BackgroundAlthough resurrecting ancestral proteins is a powerful tool for understanding the molecular-functional evolution of gene families, nearly all studies have examined proteins functioning in relatively stable biological processes. The extent to which more dynamic systems obey the same ‘rules’ governing stable processes is unclear. Here we present the first detailed investigation of the functional evolution of the RIG-like receptors (RLRs), a family of innate immune receptors that detect viral RNA in the cytoplasm.ResultsUsing kinetic binding assays and molecular dynamics simulations of ancestral proteins, we demonstrate how a small number of adaptive protein-coding changes repeatedly shifted the RNA preference of RLRs throughout animal evolution by reorganizing the shape and electrostatic distribution across the RNA binding pocket, altering the hydrogen bond network between the RLR and its RNA target. In contrast to observations of proteins involved in metabolism and development, we find that RLR-RNA preference ‘flip flopped’ between two functional states, and shifts in RNA preference were not always coupled to gene duplications or speciation events. We demonstrate at least one reversion of RLR-RNA preference from a derived to an ancestral function through a novel structural mechanism, indicating multiple structural implementations of similar functions.ConclusionsOur results suggest a model in which frequent shifts in selection pressures imposed by an evolutionary arms race preclude the long-term functional optimization observed in stable biological systems. As a result, the evolutionary dynamics of immune receptors may be less constrained by structural epistasis and historical contingency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0818-6) contains supplementary material, which is available to authorized users.

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“…The CHIKV RNA genome can trigger host pattern recognition receptors (PRRs) including endosomal Toll-like (TLR3 and TLR7) and cytoplasmic RIG-I-like (RIG-I and MDA5) receptors, which activate downstream adaptor molecules ( e.g ., TRIF, MyD88, and MAVS) to induce nuclear translocation of IRF3 and type I interferon (IFN)-dependent antiviral responses (27–29). While this scheme generally is accepted for many viruses, there are conflicting reports as to the necessity of individual PRRs in the antiviral response against CHIKV in mice.…”

Section: Innate Immune Response To Chikv Infectionmentioning

confidence: 99%

Immune-Mediated Protection and Pathogenesis of Chikungunya Virus

Fox

Diamond

2016

The Journal of Immunology

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Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes debilitating acute and chronic arthritis. Infection by CHIKV induces a robust immune response that is characterized by production of type I interferons, recruitment of innate and adaptive immune cells, and development of neutralizing antibodies. Despite this response, chronic arthritis can develop in some individuals, which may be due to a failure to eliminate viral RNA and antigen and/or persistent immune responses that cause chronic joint inflammation. In this review, based primarily on advances from recent studies in mice, we discuss the innate and adaptive immune factors that control CHIKV dissemination and clearance or contribute to pathogenesis.

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Comparative analysis of viral RNA signatures on different RIG-I-like receptors

Cited by 84 publications

References 76 publications

Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference

Immune-Mediated Protection and Pathogenesis of Chikungunya Virus

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