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Viruses
Special Issues
Regulatory Mechanisms of Viral UTRs
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Regulatory Mechanisms of Viral UTRs

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

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 14392

Special Issue Editor

Prof. Dr. Blanton S. Tolbert

E-Mail Website
Guest Editor
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
Interests: NMR spectroscopy; isothermal titration calorimetry; differential scanning calorimetry; protein chromatography; X-ray crystallography and molecular dynamics simulations

Special Issue Information

Dear Colleagues,

Viral untranslated regions (UTRs) fold into complex structures to regulate cellular stages of the replication cycles of RNA and related retroviruses. These RNA structural elements are often the most phylogenetically conserved regions of viral genomes. Viral UTRs function as control centers to coordinate a myriad of RNA–RNA, protein–RNA, and small molecule–RNA interactions that confer spatiotemporal regulation on the molecular biology of viral RNA replication. Functions such as viral RNA synthesis, viral protein translation, genome packaging, splicing, innate immunity, and others are regulated through viral UTR interactions. As such, the structures, dynamics, and interaction partners of viral UTRs represent biological systems to better understand molecular virology and targets for therapeutic interventions.

In this Special Issue, we aim to highlight the multifunctional roles of viral UTRs that lead us to posit that they act as regulatory hubs to condition the cell for optimal replication. By looking at viral UTRs through this wider lens, we anticipate that chemical biological strategies can be developed that target specific viral RNA–host interfaces and, as such, pathways.

Prof. Dr. Blanton S. Tolbert
Guest Editor

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Keywords

  • RNA viruses
  • retroviruses
  • untranslated regions
  • noncoding RNAs
  • RNA structure
  • RNA dynamics
  • protein–RNA interactions
  • IRES
  • RNA binding proteins
  • genome packaging
  • splicing
  • innate immunity

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Published Papers (4 papers)

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Research

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8 pages, 2266 KiB  
Communication
Inhibition of Cell-Free Translation and Replication of Tobacco Mosaic Virus RNA by Exogenously Added 5′-Proximal Fragments of the Genomic RNA
by Tetsuya Yoshida, Masayuki Ishikawa and Kazuhiro Ishibashi
Viruses 2022, 14(9), 1962; https://doi.org/10.3390/v14091962 - 4 Sep 2022
Viewed by 1591
Abstract
Replication proteins of tobacco mosaic virus (TMV), a positive-sense RNA virus, co-translationally bind to a 5′-proximal ~70-nucleotide (nt) region of the genomic RNA, referred to as the nuclease-resistant (NR) region for replication template selection. Therefore, disruption of the interaction between the viral replication [...] Read more.
Replication proteins of tobacco mosaic virus (TMV), a positive-sense RNA virus, co-translationally bind to a 5′-proximal ~70-nucleotide (nt) region of the genomic RNA, referred to as the nuclease-resistant (NR) region for replication template selection. Therefore, disruption of the interaction between the viral replication proteins and viral genomic RNA is expected to inhibit the replication of TMV. In this study, we demonstrate that the addition of small RNA fragments (18–33 nts in length) derived from different regions within the NR region inhibit the binding of TMV replication proteins to viral RNA and TMV RNA replication in a cell-free system. Intriguingly, some of the small RNA fragments also inhibited the translation of mRNA in a sequence-nonspecific manner. These results highlight the pleiotropic roles of the 5′-proximal region of the TMV genome. Full article
(This article belongs to the Special Issue Regulatory Mechanisms of Viral UTRs)
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17 pages, 2618 KiB  
Article
Phosphomimetic S207D Lysyl–tRNA Synthetase Binds HIV-1 5′UTR in an Open Conformation and Increases RNA Dynamics
by William A. Cantara, Chathuri Pathirage, Joshua Hatterschide, Erik D. Olson and Karin Musier-Forsyth
Viruses 2022, 14(7), 1556; https://doi.org/10.3390/v14071556 - 16 Jul 2022
Cited by 5 | Viewed by 3245
Abstract
Interactions between lysyl–tRNA synthetase (LysRS) and HIV-1 Gag facilitate selective packaging of the HIV-1 reverse transcription primer, tRNALys3. During HIV-1 infection, LysRS is phosphorylated at S207, released from a multi-aminoacyl–tRNA synthetase complex and packaged into progeny virions. LysRS is critical for [...] Read more.
Interactions between lysyl–tRNA synthetase (LysRS) and HIV-1 Gag facilitate selective packaging of the HIV-1 reverse transcription primer, tRNALys3. During HIV-1 infection, LysRS is phosphorylated at S207, released from a multi-aminoacyl–tRNA synthetase complex and packaged into progeny virions. LysRS is critical for proper targeting of tRNALys3 to the primer-binding site (PBS) by specifically binding a PBS-adjacent tRNA-like element (TLE), which promotes release of the tRNA proximal to the PBS. However, whether LysRS phosphorylation plays a role in this process remains unknown. Here, we used a combination of binding assays, RNA chemical probing, and small-angle X-ray scattering to show that both wild-type (WT) and a phosphomimetic S207D LysRS mutant bind similarly to the HIV-1 genomic RNA (gRNA) 5′UTR via direct interactions with the TLE and stem loop 1 (SL1) and have a modest preference for binding dimeric gRNA. Unlike WT, S207D LysRS bound in an open conformation and increased the dynamics of both the PBS region and SL1. A new working model is proposed wherein a dimeric phosphorylated LysRS/tRNA complex binds to a gRNA dimer to facilitate tRNA primer release and placement onto the PBS. Future anti-viral strategies that prevent this host factor-gRNA interaction are envisioned. Full article
(This article belongs to the Special Issue Regulatory Mechanisms of Viral UTRs)
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11 pages, 7013 KiB  
Article
Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System
by Emmanuelle Bignon, Marco Marazzi, Tom Miclot, Giampaolo Barone and Antonio Monari
Viruses 2022, 14(6), 1282; https://doi.org/10.3390/v14061282 - 13 Jun 2022
Cited by 5 | Viewed by 2196
Abstract
In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. [...] Read more.
In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus is a mosquito-borne pathogen that can spread to humans and induce severe neurological problems. This RNA virus caused recent remarkable outbreaks, notably in Europe, highlighting the need to investigate the molecular mechanisms of its infection process in order to design and propose efficient antivirals. Here, we resort to all-atom Molecular Dynamics simulations to characterize the structure of the 5′-untranslated region of the West Nile Virus genome and its specific recognition by the human innate immune system via oligoadenylate synthetase. Our simulations allowed us to map the interaction network between the viral RNA and the host protein, which drives its specific recognition and triggers the host immune response. These results may provide fundamental knowledge that can assist further antivirals’ design, including therapeutic RNA strategies. Full article
(This article belongs to the Special Issue Regulatory Mechanisms of Viral UTRs)
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Review

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14 pages, 983 KiB  
Review
HIV UTR, LTR, and Epigenetic Immunity
by Jielin Zhang and Clyde Crumpacker
Viruses 2022, 14(5), 1084; https://doi.org/10.3390/v14051084 - 18 May 2022
Cited by 9 | Viewed by 6486
Abstract
The duel between humans and viruses is unending. In this review, we examine the HIV RNA in the form of un-translated terminal region (UTR), the viral DNA in the form of long terminal repeat (LTR), and the immunity of human DNA in a [...] Read more.
The duel between humans and viruses is unending. In this review, we examine the HIV RNA in the form of un-translated terminal region (UTR), the viral DNA in the form of long terminal repeat (LTR), and the immunity of human DNA in a format of epigenetic regulation. We explore the ways in which the human immune responses to invading pathogenic viral nucleic acids can inhibit HIV infection, exemplified by a chromatin vaccine (cVaccine) to elicit the immunity of our genome—epigenetic immunity towards a cure. Full article
(This article belongs to the Special Issue Regulatory Mechanisms of Viral UTRs)
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