The RNA sensor MDA5 detects SARS-CoV-2 infection

Sampaio, Natália G.; Chauveau, Lise; Hertzog, Jonny; Bridgeman, Anne; Fowler, Gerissa; Moonen, Jurgen P.; Dupont, Maeva; Russel, Rebecca A; Noerenberg, Marko; Rehwinkel, Jan

doi:10.1101/2021.03.26.437180

Cited by 6 publications

(5 citation statements)

References 56 publications

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“…For most viruses, the gene expression inductor for IFN a/b is dsRNA. Many viruses generated strategies that prevent dsRNA exposure in the cytoplasm (167)(168)(169). In reoviruses, dsRNA remains inside the capsid during the whole viral cycle.…”

Section: Viral Strategies Against Ifnsmentioning

confidence: 99%

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

Mihaescu,

Chifiriuc,

Filip

et al. 2024

Front. Immunol.

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Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well as signals from damaged host cells through membrane and cytosolic receptors. The transduction of these signals triggers a personalized response, depending on the nature of the stimulus and the host’s genetics, physiological condition, and comorbidities. Interferons (IFNs) are the primary effectors of the innate immune response, and their synthesis is activated in most cells within a few hours after pathogen invasion. IFNs are primarily synthesized in infected cells, but their anti-infective effect is extended to the neighboring cells by autocrine and paracrine action. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic in 2019 was a stark reminder of the potential threat posed by newly emerging viruses. This pandemic has also triggered an overwhelming influx of research studies aiming to unveil the mechanisms of protective versus pathogenic host immune responses induced by SARS‐CoV‐2. The purpose of this review is to describe the role of IFNs as vital players in the battle against SARS‐CoV-2 infection. We will briefly characterize and classify IFNs, present the inductors of IFN synthesis, their sensors, and signaling pathways, and then discuss the role of IFNs in controlling the evolution of SARS-CoV-2 infection and its clinical outcome. Finally, we will present the perspectives and controversies regarding the prophylactic and therapeutic potential of IFNs in SARS-CoV-2 infection.

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Section: Viral Strategies Against Ifnsmentioning

confidence: 99%

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

Mihaescu,

Chifiriuc,

Filip

et al. 2024

Front. Immunol.

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“…Multiple studies reported that the RLR pathway is activated during SARS-CoV-2 infection for anti-viral responses in vitro (Kouwaki et al, 2021;Sampaio et al, 2021;Thorne et al, 2021;Wu et al, 2021;Yamada et al, 2021;Yin et al, 2021). For example, Thorne et al (2021) have reported that RNA sensing of SARS-CoV-2 in lung epithelium can contribute to robust macrophage activation, cytokine production and tissue inflammation.…”

Section: Sars-cov-2 Recognition By Rig-i-like Receptors (Rlrs) and To...mentioning

confidence: 99%

“…For example, Thorne et al (2021) have reported that RNA sensing of SARS-CoV-2 in lung epithelium can contribute to robust macrophage activation, cytokine production and tissue inflammation. Meanwhile, both Yin and Sampaio et al reported that SARS-CoV-2 is sensed by MDA5, NOD1, and LGP2, but not RIG-I and MAVS; while IRF3, IRF5, and NF-κB/p65 act as the major mediators of IFN response induction (Sampaio et al, 2021;Yin et al, 2021).…”

Section: Sars-cov-2 Recognition By Rig-i-like Receptors (Rlrs) and To...mentioning

confidence: 99%

SARS-CoV-2-mediated evasion strategies for antiviral interferon pathways

Shin

2022

J Microbiol.

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With global expansion of the COVID-19 pandemic and the emergence of new variants, extensive efforts have been made to develop highly effective antiviral drugs and vaccines against SARS-CoV-2. The interactions of coronaviruses with host antiviral interferon pathways ultimately determine successful viral replication and SARS-CoV-2-induced pathogenesis. Innate immune receptors play an essential role in host defense against SARS-CoV-2 via the induction of IFN production and signaling. Here, we summarize the recent advances in innate immune sensing mechanisms of SARS-CoV-2 and various strategies by which SARS-CoV-2 antagonizes antiviral innate immune signaling pathways, with a particular focus on mechanisms utilized by multiple SARS-CoV-2 proteins to evade interferon induction and signaling in host cell. Understanding the underlying immune evasion mechanisms of SARS-CoV-2 is essential for the improvement of vaccines and therapeutic strategies.

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“…Innate immune responses are initiated by recognizing viral PAMPs via PRRs [100] . Cytosolic RLRs including RIG-I, and MDA5, and endosomal TLRs mainly TLR-3, TLR-7, and TLR-8 are major PRRs responsible for detecting RNA virus infections such as coronaviruses and promoting the antiviral IFN pathway [101] , [102] , [103] , [104] . Ligand binding results in triggering the downstream adaptor proteins including myeloid differentiation primary response gene 88 (MyD88) and mitochondrial antiviral signaling protein (MAVS).…”

Section: Immunoediting In Sars-cov-2mentioning

confidence: 99%

Immunoediting in SARS-CoV-2: Mutual relationship between the virus and the host

Kheshtchin

Bakhshi

Arab

et al. 2022

International Immunopharmacology

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Immunoediting is a well-known concept that occurs in cancer through three steps of elimination, equilibrium, and escape (3Es), where the immune system first suppresses the growth of tumor cells and then promotes them towards the malignancy. This phenomenon has been conceptualized in some chronic viral infections such as HTLV-1 and HIV by obtaining the resistance to elimination and making a persistent form of infected cells especially in untreated patients. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a heterogeneous disease characterizing from mild/asymptomatic to severe/critical courses with some behavioral aspects in an immunoediting setting. In this context, a coordinated effort between of innate and adaptive immune system leads to detection and destruction of early infection followed by equilibrium between virus-specific responses and infected cells, which eventually end up with an uncontrolled inflammatory response in severe/critical patients. Although the SARS-CoV-2 applies several escape strategies such as mutations in viral epitopes, modulating the interferon response and inhibiting the MHC I molecules similar to the cancer cells, the 3Es hallmark may not occur in all clinical conditions. Here, we discuss how the lesson learnt from cancer immunoediting and accurate understanding of these pathophysiological mechanisms helps to develop more effective therapeutic strategies for COVID-19.

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The RNA sensor MDA5 detects SARS-CoV-2 infection

Cited by 6 publications

References 56 publications

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection

SARS-CoV-2-mediated evasion strategies for antiviral interferon pathways

Immunoediting in SARS-CoV-2: Mutual relationship between the virus and the host

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