Filovirus helical nucleocapsid structures

Hu, Shangfan; Noda, Takeshi

doi:10.1093/jmicro/dfac049

Cited by 4 publications

(13 citation statements)

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“…Additional reviews with more specific information related to the nucleocapsid and RNP structure of viruses within this family can be found in [ 23 , 24 ].…”

Section: Structure Of the Nucleocapsid Of -Ssrnavmentioning

confidence: 99%

CryoEM of Viral Ribonucleoproteins and Nucleocapsids of Single-Stranded RNA Viruses

Modrego

Carlero

Arranz

et al. 2023

Viruses

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Single-stranded RNA viruses (ssRNAv) are characterized by their biological diversity and great adaptability to different hosts; traits which make them a major threat to human health due to their potential to cause zoonotic outbreaks. A detailed understanding of the mechanisms involved in viral proliferation is essential to address the challenges posed by these pathogens. Key to these processes are ribonucleoproteins (RNPs), the genome-containing RNA-protein complexes whose function is to carry out viral transcription and replication. Structural determination of RNPs can provide crucial information on the molecular mechanisms of these processes, paving the way for the development of new, more effective strategies to control and prevent the spread of ssRNAv diseases. In this scenario, cryogenic electron microscopy (cryoEM), relying on the technical and methodological revolution it has undergone in recent years, can provide invaluable help in elucidating how these macromolecular complexes are organized, packaged within the virion, or the functional implications of these structures. In this review, we summarize some of the most prominent achievements by cryoEM in the study of RNP and nucleocapsid structures in lipid-enveloped ssRNAv.

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“…Additional reviews with more specific information related to the nucleocapsid and RNP structure of viruses within this family can be found in [ 23 , 24 ].…”

Section: Structure Of the Nucleocapsid Of -Ssrnavmentioning

confidence: 99%

CryoEM of Viral Ribonucleoproteins and Nucleocapsids of Single-Stranded RNA Viruses

Modrego

Carlero

Arranz

et al. 2023

Viruses

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“…LLOV possesses a nonsegmented, single-stranded, negative-sense RNA genome. Its viral genomic RNA (vRNA) encodes at least seven proteins: a nucleoprotein (NP), a polymerase cofactor (viral protein 35 [VP35]), a matrix protein (VP40), a glycoprotein (GP), a transcriptional activator (VP30), a nucleocapsid associated protein (VP24), and an RNA-dependent RNA polymerase (L) ( 1 , 5 , 6 ). A morphological analysis of the virus-like particles (VLPs) of the LLOV showed that the virus has a characteristic filamentous structure, like other filoviruses ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…A morphological analysis of the virus-like particles (VLPs) of the LLOV showed that the virus has a characteristic filamentous structure, like other filoviruses ( 7 ). The nucleocapsid, which is located at the center of the filamentous particles, comprises a helical structure of the NP–vRNA complex associated with VP35, VP30, VP24, and L and is responsible for transcribing and replicating the vRNA ( 6 , 8–10 ).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the overall structure of the EBOV nucleocapsid in virions was visualized at a nanometer resolution using cryoelectron tomography, demonstrating that the helical NP–RNA complex constitutes the core of the nucleocapsid ( 11 , 12 ). Single-particle cryoelectron microscopy (cryo-EM) was used to explore high-resolution structures of a C-terminally truncated EBOV NP (1–450 residues)–RNA helix and a C-terminally truncated MARV NP (1–395 residues)–RNA helix ( 6 , 13–15 ). Studies have shown that both the EBOV and MARV NPs comprise four domains: an N-terminal arm, a core domain responsible for RNA binding, a disordered linker, and a C-terminal tail that is required for the interactions with other nucleocapsid components ( 6 , 13–17 ).…”

Section: Introductionmentioning

confidence: 99%

“…Single-particle cryoelectron microscopy (cryo-EM) was used to explore high-resolution structures of a C-terminally truncated EBOV NP (1–450 residues)–RNA helix and a C-terminally truncated MARV NP (1–395 residues)–RNA helix ( 6 , 13–15 ). Studies have shown that both the EBOV and MARV NPs comprise four domains: an N-terminal arm, a core domain responsible for RNA binding, a disordered linker, and a C-terminal tail that is required for the interactions with other nucleocapsid components ( 6 , 13–17 ). However, the structural details of the LLOV NP–RNA complex remained unknown.…”

Section: Introductionmentioning

confidence: 99%

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Cryoelectron microscopic structure of the nucleoprotein–RNA complex of the European filovirus, Lloviu virus

Fujita-Fujiharu

Sugita

et al. 2023

PNAS Nexus

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Lloviu virus (LLOV) is a novel filovirus detected in Schreiber’s bats in Europe. The isolation of the infectious LLOV from bats has raised public health concerns. However, the virological and molecular characteristics of LLOV remain largely unknown. The nucleoprotein (NP) of LLOV encapsidates the viral genomic RNA to form a helical NP-RNA complex, which acts as a scaffold for nucleocapsid formation and de novo viral RNA synthesis. In this study, using single-particle cryo-electron microscopy, we determined two structures of the LLOV NP-RNA helical complex, comprising a full-length and a C-terminally truncated NP. The two helical structures were identical, demonstrating that the N-terminal region determines the helical arrangement of the NP. The LLOV NP-RNA protomers displayed a structure similar to that in the Ebola and Marburg virus, but the spatial arrangements in the helix differed. Structure-based mutational analysis identified amino acids involved in the helical assembly and viral RNA synthesis. These structures advance our understanding of the filovirus nucleocapsid formation, and provide a structural basis for the development of anti-filoviral therapeutics.

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Genomic transfers help to decipher the ancient evolution of filoviruses and interactions with vertebrate hosts

Taylor,

Barnhart

2023

Preprint

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Although several filoviruses are dangerous human pathogens, there is conflicting evidence regarding their origins and interactions with animal hosts. Here we attempt to improve this understanding using the paleoviral record over a geological time scale, protein structure predictions, tests for evolutionary maintenance, and phylogenetic methods that alleviate sources of bias and error. We found evidence for long branch attraction bias in the L gene tree for filoviruses, and that using codon-specific models and protein structural comparisons of paleoviruses ameliorated conflict and bias. We found evidence for four ancient filoviral groups, each with extant viruses and paleoviruses with open reading frames. Furthermore, we found evidence of repeated transfers of filovirus-like elements to mouse-like rodents. A filovirus-like nucleoprotein ortholog with an open reading frame was detected in three subfamilies of spalacid rodents (present since the Miocene). These elements were unique among the detected filovirus-like paleoviruses in possessing open reading frames, expression products, and evidence for purifying selection. Our finding of structural conservation over geological time for paleoviruses informs virus and paleovirus discovery methods. Our results resolve a deep conflict in the evolutionary framework for filoviruses and reveal that genomic transfers to vertebrate hosts with potentially functional co-options have been more widespread than previously appreciated.Author SummaryFiloviruses are a family of RNA viruses discovered in 1967 and notorious for spillover of the dangerous pathogens, Ebola virus and Marburg virus. However, their origins, deeper relations, diversity, and interactions with animal hosts remain controversial. Part of the confusion may be that differing rates of evolution among divergent viral lineages can create a bias termed long branch attraction (LBA). We tested for this scenario in the L protein gene sequence of filoviruses and found evidence that LBA is occurring leading to a false pairing of filovirus lineages associated with a fish and a snake. We found that using nucleotides instead of amino acids when inferring trees, paleoviral sequences with open reading frames, additional conserved genes, and comparisons of predicted protein structures can resolve the LBA. We found four major groups of filoviruses, with the paleoviral record and trees being consistent with a fish origin for the family. Moreover, we found evidence of a filovirus-like element in spalacid rodents that has been evolutionarily maintained at the open-reading frame, amino acid sequence and structural level for over 20 million years. This element was also expressed in the liver, a target of filoviral infections. We conclude that genomic interactions of filoviruses with vertebrates, including the co-option of viral genes, are more important than previously appreciated.

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Filovirus helical nucleocapsid structures

Cited by 4 publications

References 97 publications

CryoEM of Viral Ribonucleoproteins and Nucleocapsids of Single-Stranded RNA Viruses

CryoEM of Viral Ribonucleoproteins and Nucleocapsids of Single-Stranded RNA Viruses

Cryoelectron microscopic structure of the nucleoprotein–RNA complex of the European filovirus, Lloviu virus

Genomic transfers help to decipher the ancient evolution of filoviruses and interactions with vertebrate hosts

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