The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing

Snijder, Eric J.; Decroly, Étienne; Ziebuhr, John

doi:10.1016/bs.aivir.2016.08.008

Cited by 537 publications

(643 citation statements)

References 224 publications

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“…that most likely were acquired independently of the capping enzymes of other RNA viruses. Nidoviruses also gained ribonucleases and other accessory proteins that are involved in genome replication, virulence, and other aspects of the infection cycle of these largest known RNA viruses (61,(74)(75)(76).…”

Section: Evolution Of the 5 Major Branches Of Rna Viruses And Reconstmentioning

confidence: 99%

Origins and Evolution of the Global RNA Virome

Wolf

Kazlauskas

Iranzo

et al. 2018

mBio

429

333

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Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (ϩ) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (Ϫ) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from ϩRNA viruses on at least two independent occasions, whereas ϪRNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of ϩRNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy. IMPORTANCE The majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

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Section: Evolution Of the 5 Major Branches Of Rna Viruses And Reconstmentioning

confidence: 99%

Origins and Evolution of the Global RNA Virome

Wolf

Kazlauskas

Iranzo

et al. 2018

mBio

429

333

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“…Cleavage of the pp1a and pp1ab polyproteins by multiple intrinsic protease activities, in combination with −1 and −2 frameshifting in the nsp2 coding region in most arteriviruses with the exception of equine arteritis virus (EAV), results in the production of 13 to 17 non-structural proteins (nsps) (Fang et al, 2012;Li et al, 2014b;Ziebuhr et al, 2000). The common ancestry of the extremely diverged nidovirus lineages is primarily reflected in the conservation of an array of 'core replicase domains' Lauber et al, 2013;Snijder et al, 2016), which is composed of two trans-membrane proteins, the viral main protease, and -encoded downstream of the ORF1a/1b frameshift site -the RNA-dependent RNA polymerase (RdRp)-and helicase-containing subunits (Fig. 1B), with the canonical RdRp domain residing in CoV nsp12 and AV nsp9.…”

Section: Introductionmentioning

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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“…Apart from RdRP, the other nsps coded by the replicase gene also play a crucial role in CoV replication and transcription. The nsp12 encodes the RdRP domain, nsp13 encodes the helicase (Hel) domain, while the remaining nsps encode other enzyme domain and proteins such as proteinases, a putative RNA primase, a superfamily 1 helicase, an exo-and an endoribonuclease, single-stranded RNA (ssRNA)-binding proteins, and two methyltransferases (Adedeji et al, 2012;Subissi et al, 2014;Snijder et al, 2016).…”

Section: Introductionmentioning

confidence: 99%