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Viruses
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The Diverse Regulation of Transcription in Endogenous Retroviruses
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The Diverse Regulation of Transcription in Endogenous Retroviruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 5466

Special Issue Editors

Prof. Dr. Welkin Johnson

E-Mail Website
Guest Editor
Biology Department Higgins 545, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
Interests: retroviruses; endogenous retroviruses; HERV-K; gammaretroviruses; betaretroviruses; restriction factors; paleovirology; primate lentiviruses
Special Issues, Collections and Topics in MDPI journals
Dr. Zachary H. Williams

E-Mail Website
Guest Editor
Biology Department Higgins 545, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
Interests: retroviruses; endogenous retroviruses; HERV-K; gammaretroviruses; betaretroviruses; restriction factors; paleovirology; primate lentiviruses

Special Issue Information

Dear Colleagues,

Vertebrate genomes harbor thousands of endogenous retrovirus (ERV) loci, which originate as irreversible insertions of retroviral proviruses into germline DNA. Despite the accumulation of inactivating mutations, ERVs often retain features of proviruses, including partial or complete coding sequences and cis- and trans-acting regulatory elements. Residence in the genome also means that ERVs are subject to regulation by a variety of cellular processes such as epigenetic modification, transcription factor binding, and RNA interference. There are examples of ERV loci that play a role in both normal and abnormal cellular gene expression, and it is likely that ERVs have contributed in various ways to the evolution of genome structure, gene regulation, and organismal development. Consequently, ERV expression is attracting interest from researchers across the full range of biological disciplines. However, there are significant technical challenges unique to studying ERVs, and the increasingly interdisciplinary nature of the ERV research community highlights the need to develop standards for nomenclature, methodology and interpretation.

This Special Issue invites submissions related to ERV regulation, transcription and expression or the interplay between ERVs and host gene regulation, including work on human ERVs (HERVs) and ERVs of other organisms. Relevant studies of endogenous retroelements or LTR-retrotransposons are also welcome.

Prof. Dr. Welkin Johnson
Dr. Zachary H. Williams
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. 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

  • endogenous retrovirus (ERV)
  • human endogenous retrovirus (HERV)
  • HERV-K
  • long terminal repeat (LTR)
  • retrotransposon
  • exaptation
  • transcriptional silencing
  • piRNA
  • gene regulatory network
  • pluripotency
  • chromatin
  • methylation

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Published Papers (4 papers)

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Review

24 pages, 2970 KiB  
Review
piRNA Defense Against Endogenous Retroviruses
by Milky Abajorga, Leonid Yurkovetskiy and Jeremy Luban
Viruses 2024, 16(11), 1756; https://doi.org/10.3390/v16111756 - 9 Nov 2024
Viewed by 999
Abstract
Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral [...] Read more.
Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral or detrimental. If retrotransposition occurs in gametes or in the early embryo, it introduces genetic modifications that can be transmitted to the progeny and may become fixed in the germline of that species. PIWI-interacting RNAs (piRNAs) are single-stranded, 21–35 nucleotide RNAs generated by the PIWI clade of Argonaute proteins that maintain the integrity of the animal germline by silencing transposons. The sequence specific manner by which piRNAs and germline-encoded PIWI proteins repress transposons is reminiscent of CRISPR, which retains memory for invading pathogen sequences. piRNAs are processed preferentially from the unspliced transcripts of piRNA clusters. Via complementary base pairing, mature antisense piRNAs guide the PIWI clade of Argonaute proteins to transposon RNAs for degradation. Moreover, these piRNA-loaded PIWI proteins are imported into the nucleus to modulate the co-transcriptional repression of transposons by initiating histone and DNA methylation. How retroviruses that invade germ cells are first recognized as foreign by the piRNA machinery, as well as how endogenous piRNA clusters targeting the sequences of invasive genetic elements are acquired, is not known. Currently, koalas (Phascolarctos cinereus) are going through an epidemic due to the horizontal and vertical transmission of the KoRV-A gammaretrovirus. This provides an unprecedented opportunity to study how an exogenous retrovirus becomes fixed in the genome of its host, and how piRNAs targeting this retrovirus are generated in germ cells of the infected animal. Initial experiments have shown that the unspliced transcript from KoRV-A proviruses in koala testes, but not the spliced KoRV-A transcript, is directly processed into sense-strand piRNAs. The cleavage of unspliced sense-strand transcripts is thought to serve as an initial innate defense until antisense piRNAs are generated and an adaptive KoRV-A-specific genome immune response is established. Further research is expected to determine how the piRNA machinery recognizes a new foreign genetic invader, how it distinguishes between spliced and unspliced transcripts, and how a mature genome immune response is established, with both sense and antisense piRNAs and the methylation of histones and DNA at the provirus promoter. Full article
(This article belongs to the Special Issue The Diverse Regulation of Transcription in Endogenous Retroviruses)
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17 pages, 1667 KiB  
Review
Transactivation of Human Endogenous Retroviruses by Viruses
by Erin F. Evans, Ananya Saraph and Maria Tokuyama
Viruses 2024, 16(11), 1649; https://doi.org/10.3390/v16111649 - 22 Oct 2024
Viewed by 979
Abstract
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that are part the human genome and are normally silenced through epigenetic mechanisms. However, HERVs can be induced by various host and environmental factors, including viral infection, and transcriptionally active HERVs have been [...] Read more.
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that are part the human genome and are normally silenced through epigenetic mechanisms. However, HERVs can be induced by various host and environmental factors, including viral infection, and transcriptionally active HERVs have been implicated in various physiological processes. In this review, we summarize mounting evidence of transactivation of HERVs by a wide range of DNA and RNA viruses. Though a mechanistic understanding of this phenomenon and the biological implications are still largely missing, the link between exogenous and endogenous viruses is intriguing. Considering the increasing recognition of the role of viral infections in disease, understanding these interactions provides novel insights into human health. Full article
(This article belongs to the Special Issue The Diverse Regulation of Transcription in Endogenous Retroviruses)
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Figure 1

28 pages, 1108 KiB  
Review
Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control
by Abigail S. Jarosz and Julia V. Halo
Viruses 2024, 16(8), 1312; https://doi.org/10.3390/v16081312 - 17 Aug 2024
Viewed by 1186
Abstract
Endogenous retroviruses (ERVs) are the remnants of retroviral germline infections and are highly abundant in the genomes of vertebrates. At one time considered to be nothing more than inert ‘junk’ within genomes, ERVs have been tolerated within host genomes over vast timescales, and [...] Read more.
Endogenous retroviruses (ERVs) are the remnants of retroviral germline infections and are highly abundant in the genomes of vertebrates. At one time considered to be nothing more than inert ‘junk’ within genomes, ERVs have been tolerated within host genomes over vast timescales, and their study continues to reveal complex co-evolutionary histories within their respective host species. For example, multiple instances have been characterized of ERVs having been ‘borrowed’ for normal physiology, from single copies to ones involved in various regulatory networks such as innate immunity and during early development. Within the cell, the accessibility of ERVs is normally tightly controlled by epigenetic mechanisms such as DNA methylation or histone modifications. However, these silencing mechanisms of ERVs are reversible, and epigenetic alterations to the chromatin landscape can thus lead to their aberrant expression, as is observed in abnormal cellular environments such as in tumors. In this review, we focus on ERV transcriptional control and draw parallels and distinctions concerning the loss of regulation in disease, as well as their precise regulation in early development. Full article
(This article belongs to the Special Issue The Diverse Regulation of Transcription in Endogenous Retroviruses)
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19 pages, 1720 KiB  
Review
piRNA-Guided Transposon Silencing and Response to Stress in Drosophila Germline
by Samantha Ho, William Theurkauf and Nicholas Rice
Viruses 2024, 16(5), 714; https://doi.org/10.3390/v16050714 - 30 Apr 2024
Cited by 1 | Viewed by 1657
Abstract
Transposons are integral genome constituents that can be domesticated for host functions, but they also represent a significant threat to genome stability. Transposon silencing is especially critical in the germline, which is dedicated to transmitting inherited genetic material. The small Piwi-interacting RNAs (piRNAs) [...] Read more.
Transposons are integral genome constituents that can be domesticated for host functions, but they also represent a significant threat to genome stability. Transposon silencing is especially critical in the germline, which is dedicated to transmitting inherited genetic material. The small Piwi-interacting RNAs (piRNAs) have a deeply conserved function in transposon silencing in the germline. piRNA biogenesis and function are particularly well understood in Drosophila melanogaster, but some fundamental mechanisms remain elusive and there is growing evidence that the pathway is regulated in response to genotoxic and environmental stress. Here, we review transposon regulation by piRNAs and the piRNA pathway regulation in response to stress, focusing on the Drosophila female germline. Full article
(This article belongs to the Special Issue The Diverse Regulation of Transcription in Endogenous Retroviruses)
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