Biogenesis and Dynamics of the Coronavirus Replicative Structures

Hagemeijer, Marne C.; Rottier, Peter J. M.; Haan, Cornelis A. M. de

doi:10.3390/v4113245

Cited by 69 publications

(86 citation statements)

References 152 publications

(260 reference statements)

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“…A possible model proposes that DMVs may be the initial sites of active RNA synthesis early in infection, whereas at later times, after membrane connections are lost, RNA synthesis shifts to the CMs, and DMVs become end-stage products that sequester nonfunctional dsRNAs to prevent the stimulation of the innate immune response (51, 52). …”

Section: Role Of Double-membrane Vesiclesmentioning

confidence: 99%

Continuous and Discontinuous RNA Synthesis in Coronaviruses

et al. 2015

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Replication of the coronavirus genome requires continuous RNA synthesis, whereas transcription is a discontinuous process unique among RNA viruses. Transcription includes a template switch during the synthesis of subgenomic negative-strand RNAs to add a copy of the leader sequence. Coronavirus transcription is regulated by multiple factors, including the extent of base-pairing between transcription-regulating sequences of positive and negative polarity, viral and cell protein–RNA binding, and high-order RNA-RNA interactions. Coronavirus RNA synthesis is performed by a replication-transcription complex that includes viral and cell proteins that recognize cis-acting RNA elements mainly located in the highly structured 5′ and 3′ untranslated regions. In addition to many viral nonstructural proteins, the presence of cell nuclear proteins and the viral nucleocapsid protein increases virus amplification efficacy. Coronavirus RNA synthesis is connected with the formation of double-membrane vesicles and convoluted membranes. Coronaviruses encode proofreading machinery, unique in the RNA virus world, to ensure the maintenance of their large genome size.

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Section: Role Of Double-membrane Vesiclesmentioning

confidence: 99%

Continuous and Discontinuous RNA Synthesis in Coronaviruses

et al. 2015

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“…The core of the nidovirus RTC likely consists of the RdRp domaincontaining nsp and other viral RNA-binding proteins, like nsp7-10 and nsp13-16 in the case of CoVs. In the infected cell, these subunits assemble into a membrane-bound complex that is associated with a network of modified host membranes, presumably derived from the endoplasmic reticulum (reviewed in (Hagemeijer et al, 2012;Neuman et al, 2014;van der Hoeven et al, 2016)). An alternative approach to assay nidovirus RNA synthesis in vitro, without the use of purified recombinant proteins, is based on the isolation of the membrane-associated RTCs from infected cells (van Hemert et al, 2008a(van Hemert et al, , 2008b.…”

Section: Faithful Nidovirus Replication and Transcription In Vitro Anmentioning

confidence: 99%

“…in Sections 8 and 11 in more detail). Imaging and biochemical characterization of nidovirus nsps have shown that they are targeted to specific virus-induced membrane structures (reviewed in (Hagemeijer et al, 2012;Neuman et al, 2014;van der Hoeven et al, 2016)) where they assemble into a so-called replication and transcription complex (RTC; see (Neuman et al, 2014;Snijder et al, 2016;Subissi et al, 2014a) for reviews).…”

Section: Introductionmentioning

confidence: 99%

Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes

2017

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Coronaviruses and arteriviruses are distantly related human and animal pathogens that belong to the order Nidovirales. Nidoviruses are characterized by their polycistronic plus-stranded RNA genome, the production of subgenomic mRNAs and the conservation of a specific array of replicase domains, including key RNA-synthesizing enzymes. Coronaviruses (26-34 kilobases) have the largest known RNA genomes and their replication presumably requires a processive RNA-dependent RNA polymerase (RdRp) and enzymatic functions that suppress the consequences of the typically high error rate of viral RdRps. The arteriviruses have significantly smaller genomes and form an intriguing package with the coronaviruses to analyse viral RdRp evolution and function. The RdRp domain of nidoviruses resides in a cleavage product of the replicase polyprotein named non-structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all nidoviruses, the C-terminal RdRp domain is linked to a conserved N-terminal domain, which has been coined NiRAN (nidovirus RdRp-associated nucleotidyl transferase). Although no structural information is available, the functional characterization of the nidovirus RdRp and the larger enzyme complex of which it is part, has progressed significantly over the past decade. In coronaviruses several smaller, non-enzymatic nsps were characterized that direct RdRp function, while a 3'-to-5' exoribonuclease activity in nsp14 was implicated in fidelity. In arteriviruses, the nsp1 subunit was found to maintain the balance between genome replication and subgenomic mRNA production. Understanding RdRp behaviour and interactions during RNA synthesis and subsequent processing will be key to rationalising the evolutionary success of nidoviruses and the development of antiviral strategies.

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“…IBV and SARS-CoV nsp6 have been shown to activate autophagy, inducing vesicles containing Atg5 and LC3-II (Cottam et al, 2011). MHV Nsp6 colocalizes with nsp4 when co-expressed (Hagemeijer et al, 2012), suggesting that the two proteins may interact. SARS-CoV nsp6 has also been shown to interact with nsp2, nsp8, nsp9 and accessory protein 9b via yeast two-hybrid assays (von Brunn et al, 2007).…”

Section: Nsp6mentioning

confidence: 99%

Bioinformatics and functional analyses of coronavirus nonstructural proteins involved in the formation of replicative organelles

Neuman

2016

Antiviral Research

104

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Replication of eukaryotic positive-stranded RNA viruses is usually linked to the presence of membrane-associated replicative organelles. The purpose of this review is to discuss the function of proteins responsible for formation of the coronavirus replicative organelle. This will be done by identifying domains that are conserved across the order Nidovirales, and by summarizing what is known about function and structure at the level of protein domains.

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Biogenesis and Dynamics of the Coronavirus Replicative Structures

Cited by 69 publications

References 152 publications

Continuous and Discontinuous RNA Synthesis in Coronaviruses

Continuous and Discontinuous RNA Synthesis in Coronaviruses

Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes

Bioinformatics and functional analyses of coronavirus nonstructural proteins involved in the formation of replicative organelles

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