Structure and function of negative-strand RNA virus polymerase complexes

Pyle, Jesse D.; Whelan, Sean P. J.; Bloyet, Louis-Marie

doi:10.1016/bs.enz.2021.09.002

Cited by 10 publications

(10 citation statements)

References 304 publications

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“…Viral polymerases from segmented negative stranded RNA viruses (sNSVs) typically interact directly with the conserved and quasi-complementary 5′ and 3′ viral genome ends, usually referred to as the promoter 15 , 17 , 18 . We therefore sought to identify TiLV promoter regions to be able to reconstitute an active TiLV heterotrimeric complex in vitro.…”

Section: Resultsmentioning

confidence: 99%

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family

Arragain,

Pelosse,

Thompson

et al. 2023

Nat Commun

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Tilapia Lake Virus (TiLV), a recently discovered pathogen of tilapia fish, belongs to the Amnoonviridae family from the Articulavirales order. Its ten genome segments have characteristic conserved ends and encode proteins with no known homologues, apart from the segment 1, which encodes an orthomyxo-like RNA-dependent-RNA polymerase core subunit. Here we show that segments 1–3 encode respectively the PB1, PB2 and PA-like subunits of an active heterotrimeric polymerase that maintains all domains found in the distantly related influenza polymerase, despite an unprecedented overall size reduction of 40%. Multiple high-resolution cryo-EM structures of TiLV polymerase in pre-initiation, initiation and active elongation states, show how it binds the vRNA and cRNA promoters and performs RNA synthesis, with both transcriptase and replicase configurations being characterised. However, the highly truncated endonuclease-like domain appears inactive and the putative cap-binding domain is autoinhibited, emphasising that many functional aspects of TiLV polymerase remain to be elucidated.

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Section: Resultsmentioning

confidence: 99%

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family

Arragain,

Pelosse,

Thompson

et al. 2023

Nat Commun

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“…During replication, the vRNA will synthesize full-length complementary RNA (cRNA). The cRNA can be utilized as a template for synthesizing a new negative-stranded RNA from the subsequent vRNA ( Figure 1 ) [ 10 , 11 , 12 , 13 , 14 ].…”

Section: Negative-stranded Rna Virus Life Cyclesmentioning

confidence: 99%

Developments in Negative-Strand RNA Virus Reverse Genetics

Wang,

Wu,

Cao

et al. 2024

Microorganisms

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Many epidemics are caused by negative-stranded RNA viruses, leading to serious disease outbreaks that threaten human life and health. These viruses also have a significant impact on animal husbandry, resulting in substantial economic losses and jeopardizing global food security and the sustainable livelihoods of farmers. However, the pathogenic and infection mechanism of most negative-stranded RNA viruses remain unclear. Reverse genetics systems are the most powerful tools for studying viral protein function, viral gene expression regulation, viral pathogenesis, and the generation of engineered vaccines. The reverse genetics of some negative-strand viruses have been successfully constructed, while others have not. In this review, we focus on representative viruses from the Orthomyxoviridae family (IAV), the Filoviridae family (EBOV), and the Paramyxoviridae family (PPRV) to compile and summarize the existing knowledge on reverse genetics techniques for negative-strand viruses. This will provide a theoretical foundation for developing reverse genetics techniques for some negative-strand viruses.

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“…The L protein is a large, multi-domain protein, made of five globular domains linked together by flexible linkers [28,41] (for a review see [42,43]) (Figure 2B). It carries all the enzymatic activities required for transcribing and replicating the genome: RNA synthesis [5,6], mRNA cap addition [44,45], guanine-N-7-methylation of the cap, and ribose 2 O-methylation of the first nucleotide [46,47].…”

Section: Components Of the Rna Synthesis Machinerymentioning

confidence: 99%

“…Unlike the distantly related members of the Articulavirales and Bunyavirales orders for which the polymerase can directly bind the extremity of the viral genomes, the viral polymerase of mononegaviruses cannot interact with its nucleocapsid template without its cofactor P [43]. Moreover, the genomes of mononegaviruses are deeply encased in helical nucleocapsids, thus raising the question of how the polymerase accesses the RNA.…”

Section: The Nucleocapsid As a Templatementioning

confidence: 99%

The Nucleocapsid of Paramyxoviruses: Structure and Function of an Encapsidated Template

Bloyet

2021

Viruses

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Viruses of the Paramyxoviridae family share a common and complex molecular machinery for transcribing and replicating their genomes. Their non-segmented, negative-strand RNA genome is encased in a tight homopolymer of viral nucleoproteins (N). This ribonucleoprotein complex, termed a nucleocapsid, is the template of the viral polymerase complex made of the large protein (L) and its co-factor, the phosphoprotein (P). This review summarizes the current knowledge on several aspects of paramyxovirus transcription and replication, including structural and functional data on (1) the architecture of the nucleocapsid (structure of the nucleoprotein, interprotomer contacts, interaction with RNA, and organization of the disordered C-terminal tail of N), (2) the encapsidation of the genomic RNAs (structure of the nucleoprotein in complex with its chaperon P and kinetics of RNA encapsidation in vitro), and (3) the use of the nucleocapsid as a template for the polymerase complex (release of the encased RNA and interaction network allowing the progress of the polymerase complex). Finally, this review presents models of paramyxovirus transcription and replication.

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Structure and function of negative-strand RNA virus polymerase complexes

Cited by 10 publications

References 304 publications

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family

Developments in Negative-Strand RNA Virus Reverse Genetics

The Nucleocapsid of Paramyxoviruses: Structure and Function of an Encapsidated Template

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