Special Issue "Viral Subversion of Transcriptional Control"

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

Deadline for manuscript submissions: closed (31 March 2018).

Special Issue Editor

Prof. Dr. Joe S. Mymryk
Website
Guest Editor
Departments of Oncology, Otolaryngology and Microbiology & Immunology, Western University, London, Ontario, Canada
Interests: tumor virology; transcriptional control; cancer; oncogenes

Special Issue Information

Dear Colleagues,

Transcriptional control in eukaryotic cells is incredibly complex and comprises a level of regulation that is critical for virtually every cellular process. Viruses are obligate intracellular parasites, and many rely heavily on the host cell transcriptional apparatus to express their own genes. These viruses often encode proteins that divert the cellular transcriptional machinery to viral templates. In addition, some viruses encode factors that globally repress the transcription of cellular genes, which serves to maximize resources for virus progeny production. More frequently, viruses encode factors that selectively antagonize or promote the transcription of various classes of cellular genes, with the transcriptional modulation of the cellular antiviral response representing a common theme. In general, viral reprogramming of host cell transcription creates an optimal environment for virus replication and/or persistence.

In recent years, many novel and interesting mechanisms by which viruses modulate host cell transcription to promote infection have been identified. Many of these alterations contribute to viral pathogenesis. In addition, studies of viral subversion of the transcriptional apparatus have revealed key insights into the basis of normal transcriptional regulation, including the exciting area of epigenetic control of gene expression. Collectively, this research has enhanced our understanding of the complexities of transcriptional control of gene expression.

This Special Issue of Viruses is dedicated to understanding how viruses subvert cellular transcriptional control. We hope to assemble a collection of research papers and reviews that enhance our understanding of the interface between viruses and eukaryotic transcriptional regulation. Topics may include studies on the evolution and function of viral transcriptional regulators; viral mechanisms of transcriptional shutoff and direct control of the transcriptional apparatus; virally-induced epigenetic changes as a means to alter gene expression; changes in viral control of host immune responses intimately linked with transcription; and the impact of virally induced transcriptional alterations on cell fate and a variety of pathogenic outcomes of infection, including cancer.

We hope that this Special Issue will serve as a valuable resource to new and established researchers in the field, and frame important unanswered questions to focus future research efforts.

Dr. Joe Mymryk
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 papers will be 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 2000 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

  • viral reprogramming of host cell gene expression
  • viral subversion of the host cell transcriptional apparatus for the regulation of viral gene expression
  • epigenetic reprogramming of transcription during infection
  • changes in gene expression leading to viral transformation
  • changes in gene expression leading to viral evasion of the immune system
  • changes in gene expression leading to altered cell cycle control in the infected cell

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
The Influence of E1A C-Terminus on Adenovirus Replicative Cycle
Viruses 2017, 9(12), 387; https://doi.org/10.3390/v9120387 - 19 Dec 2017
Cited by 5
Abstract
Adenovirus Early 1A proteins (E1A) are crucial for initiation of the viral life cycle after infection. The E1A gene is encoded at the left end of the viral genome and consists of two exons, the first encoding 185 amino acids in the 289 [...] Read more.
Adenovirus Early 1A proteins (E1A) are crucial for initiation of the viral life cycle after infection. The E1A gene is encoded at the left end of the viral genome and consists of two exons, the first encoding 185 amino acids in the 289 residues adenovirus 5 E1A, while the second exon encodes 104 residues. The second exon-encoded region of E1A is conserved across all E1A isoforms except for the 55 residues protein, which has a unique C-terminus due to a frame shift following splicing into the second exon. This region of E1A contributes to a variety of processes including the regulation of viral and cellular gene expression, immortalization and transformation. Here we evaluated the contributions that different regions of the second exon of E1A make to the viral life cycle using deletion mutants. The region of E1A encoded by the second exon was found to be important for overall virus growth, induction of viral and cellular gene expression, viral genome replication and deregulation of the cell cycle. Efficient viral replication was found to require exon 2 and the nuclear localization signal, as loss of either resulted in severe growth deficiency. Induction of cellular DNA synthesis was also deficient with any deletion of E1A within the C-terminus even if these deletions were outside of conserved region 4. Overall, our study provides the first comprehensive insight into the contributions of the C-terminus of E1A to the replicative fitness of human adenovirus 5 in arrested lung fibroblasts. Full article
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Show Figures

Graphical abstract

Open AccessArticle
PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication
Viruses 2017, 9(9), 262; https://doi.org/10.3390/v9090262 - 20 Sep 2017
Cited by 6
Abstract
Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut [...] Read more.
Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5′-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5′-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans. Full article
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Show Figures

Graphical abstract

Open AccessArticle
Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection
Viruses 2017, 9(9), 252; https://doi.org/10.3390/v9090252 - 10 Sep 2017
Cited by 9
Abstract
Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 [...] Read more.
Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors. Full article
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis
Viruses 2018, 10(2), 82; https://doi.org/10.3390/v10020082 - 13 Feb 2018
Cited by 17
Abstract
Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA [...] Read more.
Viruses have evolved various mechanisms to evade host immunity and ensure efficient viral replication and persistence. Several DNA tumor viruses modulate host DNA methyltransferases for epigenetic dysregulation of immune-related gene expression in host cells. The host immune responses suppressed by virus-induced aberrant DNA methylation are also frequently involved in antitumor immune responses. Here, we describe viral mechanisms and virus–host interactions by which DNA tumor viruses regulate host DNA methylation to evade antiviral immunity, which may contribute to the generation of an immunosuppressive microenvironment during cancer development. Recent trials of immunotherapies have shown promising results to treat multiple cancers; however, a significant number of non-responders necessitate identifying additional targets for cancer immunotherapies. Thus, understanding immune evasion mechanisms of cancer-causing viruses may provide great insights for reversing immune suppression to prevent and treat associated cancers. Full article
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Show Figures

Figure 1

Open AccessReview
Epigenetic Regulation of Viral Biological Processes
Viruses 2017, 9(11), 346; https://doi.org/10.3390/v9110346 - 17 Nov 2017
Cited by 8
Abstract
It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic regulation in members of the polyomaviruses, adenoviruses, human papillomaviruses, hepatitis B, and herpes viruses. For each type of virus, what [...] Read more.
It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic regulation in members of the polyomaviruses, adenoviruses, human papillomaviruses, hepatitis B, and herpes viruses. For each type of virus, what is known about the roles of DNA methylation, histone modifications, nucleosome positioning, and regulatory RNA in epigenetic regulation of the virus infection will be discussed. The mechanisms used by certain viruses to dysregulate the host cell through manipulation of epigenetic processes and the role of cellular cofactors such as BRD4 that are known to be involved in epigenetic regulation of host cell pathways will also be covered. Specifically, this review will focus on the role of epigenetic regulation in maintaining viral episomes through the generation of chromatin, temporally controlling transcription from viral genes during the course of an infection, regulating latency and the switch to a lytic infection, and global dysregulation of cellular function. Full article
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Show Figures

Graphical abstract

Back to TopTop