RNA Packaging 2.0

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 12908

Special Issue Editors


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Guest Editor
Retroviral RNA Dynamics and Delivery (R2D2), Institut d’Infectiologie de Monpellier du Centre National de la Recherche, Université de Montpellier, Montpellier, France
Interests: retroviruses; RNA metabolism and trafficking

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Guest Editor
Department of Pathogen Molecular Biology, London School of Hygiene, Tropical Medicine, London, UK
Interests: molecular and structural biology orbiviruses, host-virus interaction, novel vaccines
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Baltimore Countydisabled, University of Maryland, Baltimore, MD, USA
Interests: retroviruses; RNA; packaging; genome; structure; mechanism; HIV

Special Issue Information

Dear Colleagues,

The importance of RNA viruses in global health is manifested by the pandemics they have caused in the past, and by the COVID-19 pandemic they are causing now. Their genetic diversity underlies their zoonotic potential, and makes effective vaccines and drugs a constant challenge. How RNA genomes are packaged into newly assembled virus particles remains one of the less understood aspects of RNA viruses, yet offers the potential for a shared process that could be of immense value as a therapeutic target. It is central to the virus life cycle, yet is highly challenging, as a single genome or set of genomic segments must be packaged into the confined space of the virus capsid when all other nucleic acid is excluded. In some viruses, a binding site in the viral capsid protein recognizes a specific sequence of the genome. For more complex viruses however, this simple model breaks down as many different binding sites have to be invoked, for example for multi-segmented genomes, in order to ensure one copy of each of the multiple segments is incorporated. Alternate models and supporting data for these examples are urgently needed. An emerging concept is that RNA–RNA interactions via complementarities between the segments form a complex that is packaged, rather than each RNA segment individually. Although this critical step of the virus life cycle is becoming clearer, the dynamic nature of the RNA–RNA and RNA–protein interactions required and how they are regulated remains a cutting edge field of research. How, where, and when aspects of the targeting of viral RNAs to their site of assembly remain intriguing questions.

Addressing this topic is the goal of this Special Issue of Viruses. It will serve to highlight advances in our understanding of the current and in-progress packaging mechanisms with a stimulating mix of review and original research articles that stand out from the crowd and ensure prolific citation for many years to come.

Dr. Marylène Mougel
Prof. Dr. Polly Roy
Prof. Dr. Michael Summers
Guest Editors

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Keywords

  • viral RNA
  • capsid
  • RNA–protein interaction
  • RNA–RNA interaction
  • RNA folding
  • RNA trafficking
  • nuclear export
  • RNA packaging
  • virus assembly
  • inhibition

Published Papers (4 papers)

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Review

20 pages, 943 KiB  
Review
Visualization of Retroviral Gag-Genomic RNA Cellular Interactions Leading to Genome Encapsidation and Viral Assembly: An Overview
by Serena Bernacchi
Viruses 2022, 14(2), 324; https://doi.org/10.3390/v14020324 - 05 Feb 2022
Cited by 2 | Viewed by 2351
Abstract
Retroviruses must selectively recognize their unspliced RNA genome (gRNA) among abundant cellular and spliced viral RNAs to assemble into newly formed viral particles. Retroviral gRNA packaging is governed by Gag precursors that also orchestrate all the aspects of viral assembly. Retroviral life cycles, [...] Read more.
Retroviruses must selectively recognize their unspliced RNA genome (gRNA) among abundant cellular and spliced viral RNAs to assemble into newly formed viral particles. Retroviral gRNA packaging is governed by Gag precursors that also orchestrate all the aspects of viral assembly. Retroviral life cycles, and especially the HIV-1 one, have been previously extensively analyzed by several methods, most of them based on molecular biology and biochemistry approaches. Despite these efforts, the spatio-temporal mechanisms leading to gRNA packaging and viral assembly are only partially understood. Nevertheless, in these last decades, progress in novel bioimaging microscopic approaches (as FFS, FRAP, TIRF, and wide-field microscopy) have allowed for the tracking of retroviral Gag and gRNA in living cells, thus providing important insights at high spatial and temporal resolution of the events regulating the late phases of the retroviral life cycle. Here, the implementation of these recent bioimaging tools based on highly performing strategies to label fluorescent macromolecules is described. This report also summarizes recent gains in the current understanding of the mechanisms employed by retroviral Gag polyproteins to regulate molecular mechanisms enabling gRNA packaging and the formation of retroviral particles, highlighting variations and similarities among the different retroviruses. Full article
(This article belongs to the Special Issue RNA Packaging 2.0)
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14 pages, 5799 KiB  
Review
RNA Origami: Packaging a Segmented Genome in Orbivirus Assembly and Replication
by Po-Yu Sung and Polly Roy
Viruses 2021, 13(9), 1841; https://doi.org/10.3390/v13091841 - 15 Sep 2021
Cited by 4 | Viewed by 2615
Abstract
Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent progress and describe the advancements made in understanding the genome packaging mechanism of a model nonenveloped virus, Bluetongue virus [...] Read more.
Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent progress and describe the advancements made in understanding the genome packaging mechanism of a model nonenveloped virus, Bluetongue virus (BTV), with a 10-segment (S1–S10) double-strand RNA (dsRNA) genome. BTV (multiple serotypes), a member of the Orbivirus genus in the Reoviridae family, is a notable pathogen for livestock and is responsible for significant economic losses worldwide. This has enabled the creation of an extensive set of reagents and assays, including reverse genetics, cell-free RNA packaging, and bespoke bioinformatics approaches, which can be directed to address the packaging question. Our studies have shown that (i) UTRs enable the conformation of each segment necessary for the next level of RNA–RNA interaction; (ii) a specific order of intersegment interactions leads to a complex RNA network containing all the active components in sorting and packaging; (iii) networked segments are recruited into nascent assembling capsids; and (iv) select capsid proteins might be involved in the packaging process. The key features of genome packaging mechanisms for BTV and related dsRNA viruses are novel and open up new avenues of potential intervention. Full article
(This article belongs to the Special Issue RNA Packaging 2.0)
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14 pages, 3534 KiB  
Review
Interplay between Host tRNAs and HIV-1: A Structural Perspective
by Jinwei Zhang
Viruses 2021, 13(9), 1819; https://doi.org/10.3390/v13091819 - 13 Sep 2021
Cited by 6 | Viewed by 2838
Abstract
The cellular metabolism of host tRNAs and life cycle of HIV-1 cross paths at several key virus–host interfaces. Emerging data suggest a multi-faceted interplay between host tRNAs and HIV-1 that plays essential roles, both structural and regulatory, in viral genome replication, genome packaging, [...] Read more.
The cellular metabolism of host tRNAs and life cycle of HIV-1 cross paths at several key virus–host interfaces. Emerging data suggest a multi-faceted interplay between host tRNAs and HIV-1 that plays essential roles, both structural and regulatory, in viral genome replication, genome packaging, and virion biogenesis. HIV-1 not only hijacks host tRNAs and transforms them into obligatory reverse transcription primers but further commandeers tRNAs to regulate the localization of its major structural protein, Gag, via a specific interface. This review highlights recent advances in understanding tRNA–HIV-1 interactions, primarily from a structural perspective, which start to elucidate their underlying molecular mechanisms, intrinsic specificities, and biological significances. Such understanding may provide new avenues toward developing HIV/AIDS treatments and therapeutics including small molecules and RNA biologics that target these host–virus interfaces. Full article
(This article belongs to the Special Issue RNA Packaging 2.0)
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20 pages, 2126 KiB  
Review
RNA Structures and Their Role in Selective Genome Packaging
by Liqing Ye, Uddhav B. Ambi, Marco Olguin-Nava, Anne-Sophie Gribling-Burrer, Shazeb Ahmad, Patrick Bohn, Melanie M. Weber and Redmond P. Smyth
Viruses 2021, 13(9), 1788; https://doi.org/10.3390/v13091788 - 08 Sep 2021
Cited by 6 | Viewed by 4031
Abstract
To generate infectious viral particles, viruses must specifically select their genomic RNA from milieu that contains a complex mixture of cellular or non-genomic viral RNAs. In this review, we focus on the role of viral encoded RNA structures in genome packaging. We first [...] Read more.
To generate infectious viral particles, viruses must specifically select their genomic RNA from milieu that contains a complex mixture of cellular or non-genomic viral RNAs. In this review, we focus on the role of viral encoded RNA structures in genome packaging. We first discuss how packaging signals are constructed from local and long-range base pairings within viral genomes, as well as inter-molecular interactions between viral and host RNAs. Then, how genome packaging is regulated by the biophysical properties of RNA. Finally, we examine the impact of RNA packaging signals on viral evolution. Full article
(This article belongs to the Special Issue RNA Packaging 2.0)
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