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ncRNA
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Non-Coding RNAs in Viral Infections
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Non-Coding RNAs in Viral Infections

A special issue of Non-Coding RNA (ISSN 2311-553X). This special issue belongs to the section "Detection and Biomarkers of Non-Coding RNA".

Deadline for manuscript submissions: closed (21 September 2018) | Viewed by 52789

Special Issue Editors

Dr. Rebecca Skalsky

E-Mail Website
Guest Editor
Vaccine and Gene Therapy Institute, Beaverton, OR, USA
Interests: microRNAs; non-coding RNAs; virus–host interactions; DNA tumor viruses
Dr. Eva Gottwein

E-Mail Website
Guest Editor
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Interests: microRNAs; human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV)

Special Issue Information

Dear Colleagues,

Non-coding RNAs (ncRNAs) are key regulators in anti-viral responses and play diverse roles in various aspects of infection, including virus replication, persistence, and pathogenesis. In addition to host ncRNAs that are influenced and/or utilized during infection, both DNA and RNA viruses produce regulatory ncRNAs. These molecules can act to modulate gene expression, such as microRNAs encoded by several DNA viruses, or control RNA stability or epigenetic processes, such as some viral long ncRNAs. Ongoing questions include how viral ncRNAs contribute to immune evasion, whether ncRNAs act as virulence factors, how viruses hijack host ncRNAs, and how both viral and host ncRNAs coordinate to benefit virus replication.

This Special Issue will group together works on the latest advances in non-coding RNA studies related to virus infections in humans and animal model systems.

For this Special Issue, we will consider manuscripts on the following topics:

  • ncRNAs, including miRNAs, as regulators of cell signaling and anti-viral responses
  • novel functions of viral or host ncRNAs in virus replication
  • ncRNAs in viral pathogenesis
  • pre-clinical and clinical studies investigating the roles of ncRNAs in viral diseases

Dr. Rebecca Skalsky
Dr. Eva Gottwein
Guest Editors

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. Non-Coding RNA is an international peer-reviewed open access semimonthly 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 1800 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

  • virus
  • non-coding RNA
  • microRNAs
  • host–pathogen interactions
  • innate immunity
  • chronic infection
  • viral persistence

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (8 papers)

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Research

Jump to: Review

14 pages, 2149 KiB  
Article
Gammaherpesvirus Readthrough Transcription Generates a Long Non-Coding RNA That Is Regulated by Antisense miRNAs and Correlates with Enhanced Lytic Replication In Vivo
by Mehmet Kara, Tina O’Grady, Emily R. Feldman, April Feswick, Yiping Wang, Erik K. Flemington and Scott A. Tibbetts
Non-Coding RNA 2019, 5(1), 6; https://doi.org/10.3390/ncrna5010006 - 10 Jan 2019
Cited by 10 | Viewed by 5575
Abstract
Gammaherpesviruses, including the human pathogens Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are oncogenic viruses that establish lifelong infections in hosts and are associated with the development of lymphoproliferative diseases and lymphomas. Recent studies have shown that the majority of the mammalian [...] Read more.
Gammaherpesviruses, including the human pathogens Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are oncogenic viruses that establish lifelong infections in hosts and are associated with the development of lymphoproliferative diseases and lymphomas. Recent studies have shown that the majority of the mammalian genome is transcribed and gives rise to numerous long non-coding RNAs (lncRNAs). Likewise, the large double-stranded DNA virus genomes of herpesviruses undergo pervasive transcription, including the expression of many as yet uncharacterized lncRNAs. Murine gammaperherpesvirus 68 (MHV68, MuHV-4, γHV68) is a natural pathogen of rodents, and is genetically and pathogenically related to EBV and KSHV, providing a highly tractable model for studies of gammaherpesvirus biology and pathogenesis. Through the integrated use of parallel data sets from multiple sequencing platforms, we previously resolved transcripts throughout the MHV68 genome, including at least 144 novel transcript isoforms. Here, we sought to molecularly validate novel transcripts identified within the M3/M2 locus, which harbors genes that code for the chemokine binding protein M3, the latency B cell signaling protein M2, and 10 microRNAs (miRNAs). Using strand-specific northern blots, we validated the presence of M3-04, a 3.91 kb polyadenylated transcript that initiates at the M3 transcription start site and reads through the M3 open reading frame (ORF), the M3 poly(a) signal sequence, and the M2 ORF. This unexpected transcript was solely localized to the nucleus, strongly suggesting that it is not translated and instead may function as a lncRNA. Use of an MHV68 mutant lacking two M3-04-antisense pre-miRNA stem loops resulted in highly increased expression of M3-04 and increased virus replication in the lungs of infected mice, demonstrating a key role for these RNAs in regulation of lytic infection. Together these findings suggest the possibility of a tripartite regulatory relationship between the lncRNA M3-04, antisense miRNAs, and the latency gene M2. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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Review

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13 pages, 4243 KiB  
Review
Multifunctional miR-155 Pathway in Avian Oncogenic Virus-Induced Neoplastic Diseases
by Megha Sravani Bondada, Yongxiu Yao and Venugopal Nair
Non-Coding RNA 2019, 5(1), 24; https://doi.org/10.3390/ncrna5010024 - 13 Mar 2019
Cited by 20 | Viewed by 6084
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that fine-tune the responses of the cell by modulating the cell transcriptome and gene expression. MicroRNA 155 (miR-155) is a conserved multifunctional miRNA involved in multiple roles including the modulation of the immune responses. When deregulated, miR-155 [...] Read more.
MicroRNAs (miRNAs) are small noncoding RNAs that fine-tune the responses of the cell by modulating the cell transcriptome and gene expression. MicroRNA 155 (miR-155) is a conserved multifunctional miRNA involved in multiple roles including the modulation of the immune responses. When deregulated, miR-155 can also contribute to cancer as has been demonstrated in several human malignancies such as diffuse large B cell lymphoma, chronic lymphocytic leukemia, as well as in Epstein–Barr virus (EBV)-induced B cell transformation. Avian oncogenic viruses such as Marek’s disease virus (MDV), avian leukosis virus (ALV), and reticuloendotheliosis virus (REV) that account for more than 90% of cancers in avian species, also make use of the miR-155 pathway during oncogenesis. While oncogenic retroviruses, such as ALV, activate miR-155 by insertional activation, acutely transforming retroviruses use transduced oncogenes such as v-rel to upregulate miR-155 expression. MDV on the other hand, encodes a functional miR-155 ortholog mdv1-miR-M4, similar to the miR-155 ortholog kshv-miR-K11 present in Kaposi’s sarcoma-associated herpesvirus (KSHV). We have shown that mdv1-miR-M4 is critical for the induction of MDV-induced lymphomas further demonstrating the oncogenic potential of miR-155 pathway in cancers irrespective of the diverse etiology. In this review, we discuss on our current understanding of miR-155 function in virus-induced lymphomas focusing primarily on avian oncogenic viruses. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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25 pages, 1325 KiB  
Review
Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals
by Nkerorema Djodji Damas, Nicolas Fossat and Troels K. H. Scheel
Non-Coding RNA 2019, 5(1), 7; https://doi.org/10.3390/ncrna5010007 - 14 Jan 2019
Cited by 39 | Viewed by 6935
Abstract
Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of [...] Read more.
Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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21 pages, 1438 KiB  
Review
Herpes Simplex Virus 1 Deregulation of Host MicroRNAs
by Maja Cokarić Brdovčak, Andreja Zubković and Igor Jurak
Non-Coding RNA 2018, 4(4), 36; https://doi.org/10.3390/ncrna4040036 - 23 Nov 2018
Cited by 33 | Viewed by 7498
Abstract
Viruses utilize microRNAs (miRNAs) in a vast variety of possible interactions and mechanisms, apparently far beyond the classical understanding of gene repression in humans. Likewise, herpes simplex virus 1 (HSV-1) expresses numerous miRNAs and deregulates the expression of host miRNAs. Several HSV-1 miRNAs [...] Read more.
Viruses utilize microRNAs (miRNAs) in a vast variety of possible interactions and mechanisms, apparently far beyond the classical understanding of gene repression in humans. Likewise, herpes simplex virus 1 (HSV-1) expresses numerous miRNAs and deregulates the expression of host miRNAs. Several HSV-1 miRNAs are abundantly expressed in latency, some of which are encoded antisense to transcripts of important productive infection genes, indicating their roles in repressing the productive cycle and/or in maintenance/reactivation from latency. In addition, HSV-1 also exploits host miRNAs to advance its replication or repress its genes to facilitate latency. Here, we discuss what is known about the functional interplay between HSV-1 and the host miRNA machinery, potential targets, and the molecular mechanisms leading to an efficient virus replication and spread. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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12 pages, 1051 KiB  
Review
Contemporary Ribonomics Methods for Viral microRNA Target Analysis
by Lauren A. Gay, Peter C. Turner and Rolf Renne
Non-Coding RNA 2018, 4(4), 31; https://doi.org/10.3390/ncrna4040031 - 9 Nov 2018
Cited by 5 | Viewed by 6316
Abstract
Numerous cellular processes are regulated by microRNAs (miRNAs), both cellular and viral. Elucidating the targets of miRNAs has become an active area of research. An important method in this field is cross-linking and immunoprecipitation (CLIP), where cultured cells or tissues are UV-irradiated to [...] Read more.
Numerous cellular processes are regulated by microRNAs (miRNAs), both cellular and viral. Elucidating the targets of miRNAs has become an active area of research. An important method in this field is cross-linking and immunoprecipitation (CLIP), where cultured cells or tissues are UV-irradiated to cross-link protein and nucleic acid, the RNA binding protein of interest is immunoprecipitated, and the RNAs pulled down with the protein are isolated, reverse-transcribed, and analyzed by sequencing. CLIP using antibody against Argonaute (Ago), which binds to both miRNA and mRNA as they interact in RISC, has allowed researchers to uncover a large number of miRNA targets. Coupled with high-throughput sequencing, CLIP has been useful for revealing miRNA targetomes for the γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). Variants on the CLIP protocol are described, with the benefits and drawbacks of each. In particular, the most recent methods involving RNA–RNA ligation to join the miRNA and its RNA target have aided in target identification. Lastly, data supporting biologically meaningful interactions between miRNAs and long non-coding RNAs (lncRNAs) are reviewed. In summary, ribonomics-based miRNA targetome analysis has expanded our understanding of miRNA targeting and has provided a rich resource for EBV and KSHV research with respect to pathogenesis and tumorigenesis. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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19 pages, 1508 KiB  
Review
HCMV miRNA Targets Reveal Important Cellular Pathways for Viral Replication, Latency, and Reactivation
by Nicole L. Diggins and Meaghan H. Hancock
Non-Coding RNA 2018, 4(4), 29; https://doi.org/10.3390/ncrna4040029 - 22 Oct 2018
Cited by 32 | Viewed by 5478
Abstract
It is now well appreciated that microRNAs (miRNAs) play a critical role in the lifecycles of many herpes viruses. The human cytomegalovirus (HCMV) replication cycle varies significantly depending on the cell type infected, with lytic replication occurring in fully-differentiated cells such as fibroblasts, [...] Read more.
It is now well appreciated that microRNAs (miRNAs) play a critical role in the lifecycles of many herpes viruses. The human cytomegalovirus (HCMV) replication cycle varies significantly depending on the cell type infected, with lytic replication occurring in fully-differentiated cells such as fibroblasts, endothelial cells, or macrophages, and latent infection occurring in less-differentiated CD14+ monocytes and CD34+ hematopoietic progenitor cells where viral gene expression is severely diminished and progeny virus is not produced. Given their non-immunogenic nature and their capacity to target numerous cellular and viral transcripts, miRNAs represent a particularly advantageous means for HCMV to manipulate viral gene expression and cellular signaling pathways during lytic and latent infection. This review will focus on our current knowledge of HCMV miRNA viral and cellular targets, and discuss their importance in lytic and latent infection, highlight the challenges of studying HCMV miRNAs, and describe how viral miRNAs can help us to better understand the cellular processes involved in HCMV latency. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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10 pages, 791 KiB  
Review
MicroRNA-Attenuated Virus Vaccines
by Elizabeth J. Fay and Ryan A. Langlois
Non-Coding RNA 2018, 4(4), 25; https://doi.org/10.3390/ncrna4040025 - 2 Oct 2018
Cited by 20 | Viewed by 6668
Abstract
Live-attenuated vaccines are the most effective way to establish robust, long-lasting immunity against viruses. However, the possibility of reversion to wild type replication and pathogenicity raises concerns over the safety of these vaccines. The use of host-derived microRNAs (miRNAs) to attenuate viruses has [...] Read more.
Live-attenuated vaccines are the most effective way to establish robust, long-lasting immunity against viruses. However, the possibility of reversion to wild type replication and pathogenicity raises concerns over the safety of these vaccines. The use of host-derived microRNAs (miRNAs) to attenuate viruses has been accomplished in an array of biological contexts. The broad assortment of effective tissue- and species-specific miRNAs, and the ability to target a virus with multiple miRNAs, allow for targeting to be tailored to the virus of interest. While escape is always a concern, effective strategies have been developed to improve the safety and stability of miRNA-attenuated viruses. In this review, we discuss the various approaches that have been used to engineer miRNA-attenuated viruses, the steps that have been taken to improve their safety, and the potential use of these viruses as vaccines. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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20 pages, 3083 KiB  
Review
The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis
by Gabriela Chavez-Calvillo, Sarah Martin, Chad Hamm and Joanna Sztuba-Solinska
Non-Coding RNA 2018, 4(4), 24; https://doi.org/10.3390/ncrna4040024 - 26 Sep 2018
Cited by 13 | Viewed by 6231
Abstract
Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, [...] Read more.
Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship. Full article
(This article belongs to the Special Issue Non-Coding RNAs in Viral Infections)
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