Targeting liquid–liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity

Wang, Shuai; Dai, Tong; Qin, Ziran; Pan, Ting; Feng, Cuiping; Lou, Lingfeng; Zhang, Long; Yang, Bing; Huang, Huizhe; Lu, Huasong; Zhou, Fangfang

doi:10.1038/s41556-021-00710-0

Cited by 167 publications

(155 citation statements)

References 76 publications

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“…Another study showed that the Mpro shows similar proteasome functionality as the main protease of SARS-CoV-2 (Wu et al, 2020). Recently, a study identified that SARS-CoV-2 nucleocapsid protein induces innate immune evasion by inhibiting K63-linked poly-ubiquitination and aggregation of MAVS (Wang et al, 2021). These works indicate MAVS plays an important role in the host against SARS-Cov-2 infection.…”

Section: Virus Immune Evasion Against Rig-i-mavsmentioning

confidence: 94%

MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

Chen

Shi

et al. 2021

Front. Microbiol.

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Mitochondrial antiviral signaling protein (MAVS) functions as a “switch” in the immune signal transduction against most RNA viruses. Upon viral infection, MAVS forms prion-like aggregates by receiving the cytosolic RNA sensor retinoic acid-inducible gene I-activated signaling and further activates/switches on the type I interferon signaling. While under resting state, MAVS is prevented from spontaneously aggregating to switch off the signal transduction and maintain immune homeostasis. Due to the dual role in antiviral signal transduction and immune homeostasis, MAVS has emerged as the central regulation target by both viruses and hosts. Recently, researchers show increasing interest in viral evasion strategies and immune homeostasis regulations targeting MAVS, especially focusing on the post-translational modifications of MAVS, such as ubiquitination and phosphorylation. This review summarizes the regulations of MAVS in antiviral innate immune signaling transduction and immune homeostasis maintenance.

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Section: Virus Immune Evasion Against Rig-i-mavsmentioning

confidence: 94%

MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

Chen

Shi

et al. 2021

Front. Microbiol.

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“…where V is the measured volume of the object. The index ranges from 1 (perfect sphere) to 0 (elongated shape) [47].…”

Section: Stacks Processing and Quantificationmentioning

confidence: 99%

“…LLPS has been reported as a mechanism for the assembly of virus-induced intracellular compartments for viruses of the order Mononegavirales, for the dsRNA rotaviruses, influenza viruses, coronaviruses, retroviruses and herpesviruses [29,[41][42][43][44][45]. Detailed insights into mechanisms of virus-induced assembly of cellular compartments is paramount to understand essential aspects of their biology, to learn how viruses hijack infected cells and to study fundamental mechanisms that may be common in virus-host cell interactions, which should in turn help to develop antiviral strategies and improve the use of viruses as vectors for vaccines or gene and anticancer therapies [46,47].…”

Section: Introductionmentioning

confidence: 99%

Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments

Hidalgo

Pimentel

Mojica-Santamaría

et al. 2021

Viruses

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A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions.

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“…This demonstrates that for L packaging, the biophysical properties of RNA-protein interaction are as im protein-RNA affinities. LLPS likely promotes viral assembly by enhancing i tween RNA and N protein within a privileged site [62], but may have othe replication, such as hiding viral RNA from cellular immune sensors [74,75] Coronaviruses (CoV) have extraordinarily large genomes (~30 kb) that presumably pose additional difficulties for packaging, yet genomic RNA is efficiently and selectively incorporated into virions [5,[59][60][61]. Accumulating evidence suggests that SARS-CoV-2 exploits liquid-liquid phase separation (LLPS) during its replication [62][63][64][65][66][67][68][69][70] (Figure 3).…”

Section: Packaging Signals In Rna Virusesmentioning

confidence: 99%

“…This demonstrates that for LLPS mediated packaging, the biophysical properties of RNA-protein interaction are as important as the protein-RNA affinities. LLPS likely promotes viral assembly by enhancing interaction be tween RNA and N protein within a privileged site [62], but may have other roles in vira replication, such as hiding viral RNA from cellular immune sensors [74,75].…”

Section: Packaging Signals In Rna Virusesmentioning

confidence: 99%

RNA Structures and Their Role in Selective Genome Packaging

Ambi

Olguin-Nava

et al. 2021

Viruses

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To generate infectious viral particles, viruses must specifically select their genomic RNA from milieu that contains a complex mixture of cellular or non-genomic viral RNAs. In this review, we focus on the role of viral encoded RNA structures in genome packaging. We first discuss how packaging signals are constructed from local and long-range base pairings within viral genomes, as well as inter-molecular interactions between viral and host RNAs. Then, how genome packaging is regulated by the biophysical properties of RNA. Finally, we examine the impact of RNA packaging signals on viral evolution.

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Targeting liquid–liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity

Cited by 167 publications

References 76 publications

MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments

RNA Structures and Their Role in Selective Genome Packaging

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