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Structure-Function Relationships in Viral Polymerases

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A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (15 October 2017) | Viewed by 55189

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Special Issue Editor

Dr. Olve Peersen

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Guest Editor

Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA
Interests: RNA virus replication complexes; polymerase fidelity; structural biology; enzyme kinetics

Special Issue Information

Dear Colleague,

Over the past decade our structural biology knowledge of viral polymerases and the detailed molecular interactions involved in viral genome replication has increased dramatically. We are well poised for a global comparison of these structures that highlights both commonalities among and within virus families and the unique and important aspects of individual structures. Thus, this Special Issue of Viruses is focused on viral polymerase structures and our understanding of their molecular mechanisms. The manuscripts will embrace structural biology, but they need not be strictly structure based; for example, a biochemically oriented research or review paper that leans more toward the function side of structure-function studies would be welcome.

This issue will be accompanied by an extensive collection of on-line materials in the form of movies that illustrate key elements of individual polymerase structures and comparisons of multiple structures. This is perhaps the most effective way to instil an appreciation for structure, especially for a more general virologist audience. As editor, I will work closely with the authors to develop a consistent set of molecular representations that facilitate comparisons of different polymerases. Examples of common themes to be highlighted are downstream and upstream nucleic acid interactions, strand separation mechanisms, initiation mechanisms, active site interactions and dynamics during catalysis, nucleotide selectivity, and translocation events. Suggestions for additional themes are welcome.
Guidelines for manuscript submission are shown below and authors specifically interested in partaking in the multimedia aspects of this Special Issue should contact the guest editor directly ([email protected]) for initial guidance about manuscript sections and organization.

Dr. Olve Peersen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

polymerase structure
replication

Related Special Issues

Viral Replication Complexes: Structures, Functions, Applications and Inhibitors in Viruses (18 articles)
Viral Replication Complexes in Viruses (12 articles)

Published Papers (7 papers)

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Review

17 pages, 8642 KiB

Open AccessReview

A Comprehensive Superposition of Viral Polymerase Structures

by Olve B. Peersen

Viruses 2019, 11(8), 745; https://doi.org/10.3390/v11080745 - 13 Aug 2019

Cited by 32 | Viewed by 5626

Abstract

Nucleic acid polymerases are essential enzymes that replicate the genomes of both RNA and DNA viruses. These enzymes are generally encoded by viruses themselves so as to provide biochemical functions and control elements that differ from those of the host cell polymerases. The core active site structure used by all replicative polymerases is highly conserved and composed of two key aspartate residues from the conserved motifs A and C, but beyond this there is significant divergence among structures. These differences can make it difficult to select which portions of structures to align for comparisons, yet there are extended structural similarities within different groups of viral polymerases that should clearly be considered to generate optimal alignments. This manuscript describes a comprehensive structure-based superposition of every viral polymerase structure solved thus far based on an alignment-tree approach wherein aligned regions grow in complexity as similarity among polymerases increases. The result is a set of 646 structures that have been aligned into a single common orientation. This provides a convenient resource for directly comparing viral polymerases and illustrating structural conservation among them. It also sets the stage for detailed bioinformatics analysis to further assess common structural features. The full set of protein data bank (PDB) formatted files is publicly available via the Polymerase Structures community page at the Zenodo.org open data repository. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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29 pages, 6111 KiB

Open AccessReview

Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine

by Luis Martínez-Sobrido, Olve Peersen and Aitor Nogales

Viruses 2018, 10(10), 560; https://doi.org/10.3390/v10100560 - 15 Oct 2018

Cited by 32 | Viewed by 6518

Abstract

Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures. These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans. In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases. Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses. Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections. For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV. In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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23 pages, 3015 KiB

Open AccessReview

RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution

by Sangita Venkataraman, Burra V. L. S. Prasad and Ramasamy Selvarajan

Viruses 2018, 10(2), 76; https://doi.org/10.3390/v10020076 - 10 Feb 2018

Cited by 239 | Viewed by 16716

Abstract

RNA dependent RNA polymerase (RdRp) is one of the most versatile enzymes of RNA viruses that is indispensable for replicating the genome as well as for carrying out transcription. The core structural features of RdRps are conserved, despite the divergence in their sequences. The structure of RdRp resembles that of a cupped right hand and consists of fingers, palm and thumb subdomains. The catalysis involves the participation of conserved aspartates and divalent metal ions. Complexes of RdRps with substrates, inhibitors and metal ions provide a comprehensive view of their functional mechanism and offer valuable insights regarding the development of antivirals. In this article, we provide an overview of the structural aspects of RdRps and their complexes from the Group III, IV and V viruses and their structure-based phylogeny. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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24 pages, 5188 KiB

Open AccessReview

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases

by Barbara Selisko, Nicolas Papageorgiou, François Ferron and Bruno Canard

Viruses 2018, 10(2), 59; https://doi.org/10.3390/v10020059 - 30 Jan 2018

Cited by 42 | Viewed by 5272

Abstract

Viral RNA-dependent RNA polymerases (RdRps) play a central role not only in viral replication, but also in the genetic evolution of viral RNAs. After binding to an RNA template and selecting 5′-triphosphate ribonucleosides, viral RdRps synthesize an RNA copy according to Watson-Crick base-pairing rules. The copy process sometimes deviates from both the base-pairing rules specified by the template and the natural ribose selectivity and, thus, the process is error-prone due to the intrinsic (in)fidelity of viral RdRps. These enzymes share a number of conserved amino-acid sequence strings, called motifs A–G, which can be defined from a structural and functional point-of-view. A co-relation is gradually emerging between mutations in these motifs and viral genome evolution or observed mutation rates. Here, we review our current knowledge on these motifs and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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Figure 1

7 pages, 1090 KiB

Open AccessReview

Visualizing the Nucleotide Addition Cycle of Viral RNA-Dependent RNA Polymerase

by Jiqin Wu and Peng Gong

Viruses 2018, 10(1), 24; https://doi.org/10.3390/v10010024 - 04 Jan 2018

Cited by 12 | Viewed by 5609

Abstract

Viral RNA-dependent RNA polymerases (RdRPs) are a class of nucleic acid polymerases bearing unique features from global architecture to catalytic mechanisms. In recent years, numerous viral RdRP crystal structures have improved the understanding of these molecular machines, in particular, for how they carry out each nucleotide addition cycle (NAC) as directed by the RNA template. This review focuses on a visual introduction of viral RdRP NAC mechanisms through a combination of static pictures of structural models, a user-friendly software-based assembly of the structural models, and two videos illustrating key conformational changes in the NAC. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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3322 KiB

Open AccessReview

Structure and Function of Caliciviral RNA Polymerases

by Ji-Hye Lee, Mi Sook Chung and Kyung Hyun Kim

Viruses 2017, 9(11), 329; https://doi.org/10.3390/v9110329 - 06 Nov 2017

Cited by 14 | Viewed by 6517

Abstract

Caliciviruses are a leading agent of human and animal gastroenteritis and respiratory tract infections, which are growing concerns in immunocompromised individuals. However, no vaccines or therapeutics are yet available. Since the rapid rate of genetic evolution of caliciviruses is mainly due to the error-prone nature of RNA-dependent RNA polymerase (RdRp), this article focuses on recent studies of the structures and functions of RdRp from caliciviruses. It also provides recent advances in the interactions of RdRp with virion protein genome-linked (VPg) and RNA and the structural and functional features of its precursor. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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969 KiB

Open AccessReview

The Battle of RNA Synthesis: Virus versus Host

by Alex Harwig, Robert Landick and Ben Berkhout

Viruses 2017, 9(10), 309; https://doi.org/10.3390/v9100309 - 21 Oct 2017

Cited by 26 | Viewed by 7902

Abstract

Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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