Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Herpes Simplex Virus: From Reactivation to Assembly

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 36516

Share This Special Issue

Special Issue Editor

Dr. Russell J. Diefenbach

E-Mail Website
Guest Editor

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia
Interests: herpesviruses; virus assembly; cancer liquid biopsy

Special Issue Information

Dear Colleagues,

Herpes simplex viruses type 1 and 2 (HSV-1, HSV-2) are important human pathogens. HSV-1 is carried by 45%–90% of the population, with the highest prevalence in the developing world. Primary infection usually occurs at an early age, resulting in the establishment of latent infections in sensory neurons. Periodically, the virus can reactivate, causing renewed episodes of clinical disease that enable transmission between individuals. Current antivirals target HSV DNA replication during the viral lifecycle. The emerging threat of antiviral resistance among viral isolates in immunocompromised patients has created a drive for the development of new anti-HSV compounds. Vaccine research has produced many HSV vaccine candidates, but these have ultimately failed at human clinical trial stages. Therefore, ongoing investigation of the virus–host interactions involved during the lifecycle of HSV will inform our understanding of crucial steps such as viral reactivation and assembly. This has the potential to lead to novel therapeutic options and attenuated vaccine candidates. With this in mind, submissions are invited to this Special Issue that have a focus on HSV–host interactions, particularly in the context of viral nuclear egress, secondary envelopment, and reactivation from latency.

Dr. Russell J. Diefenbach
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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

herpes simplex virus
vaccine
antiviral
latency
reactivation
nuclear egress
secondary envelopment

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

17 pages, 2394 KiB

Open AccessArticle

The HSV-1 Transcription Factor ICP4 Confers Liquid-Like Properties to Viral Replication Compartments

by Michael Seyffert, Fanny Georgi, Kurt Tobler, Laurent Bourqui, Michela Anfossi, Kevin Michaelsen, Bernd Vogt, Urs F. Greber and Cornel Fraefel

Int. J. Mol. Sci. 2021, 22(9), 4447; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094447 - 24 Apr 2021

Cited by 27 | Viewed by 4162

Abstract

Herpes Simplex Virus Type-1 (HSV-1) forms progeny in the nucleus within distinct membrane-less inclusions, the viral replication compartments (VRCs), where viral gene expression, DNA replication, and packaging occur. The way in which the VRCs maintain spatial integrity remains unresolved. Here, we demonstrate that the essential viral transcription factor ICP4 is an intrinsically disordered protein (IDP) capable of driving protein condensation and liquid–liquid phase separation (LLPS) in transfected cells. Particularly, ICP4 forms nuclear liquid-like condensates in a dose- and time-dependent manner. Fluorescence recovery after photobleaching (FRAP) assays revealed rapid exchange rates of EYFP-ICP4 between phase-separated condensates and the surroundings, akin to other viral IDPs that drive LLPS. Likewise, HSV-1 VRCs revealed by EYFP-tagged ICP4 retained their liquid-like nature, suggesting that they are phase-separated condensates. Individual VRCs homotypically fused when reaching close proximity and grew over the course of infection. Together, the results of this study demonstrate that the HSV-1 transcription factor ICP4 has characteristics of a viral IDP, forms condensates in the cell nucleus by LLPS, and can be used as a proxy for HSV-1 VRCs with characteristics of liquid–liquid phase-separated condensates. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures

Figure 1

13 pages, 1451 KiB

Open AccessArticle

Inhibition of Stress-Induced Viral Promoters by a Bovine Herpesvirus 1 Non-Coding RNA and the Cellular Transcription Factor, β-Catenin

by Jing Zhao, Nishani Wijesekera and Clinton Jones

Int. J. Mol. Sci. 2021, 22(2), 519; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020519 - 07 Jan 2021

Cited by 4 | Viewed by 2104

Abstract

The ability to establish, maintain, and reactivate from latency in sensory neurons within trigeminal ganglia (TG) is crucial for bovine herpesvirus 1 (BoHV-1) transmission. In contrast to lytic infection, the only viral gene abundantly expressed during latency is the latency-related (LR) gene. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency, in part because the glucocorticoid receptor (GR) transactivates viral promoters that drive expression of key viral transcriptional regulator proteins (bICP0 and bICP4). Within hours after dexamethasone treatment of latently infected calves, LR gene products and β-catenin are not readily detected in TG neurons. Hence, we hypothesized that LR gene products and/or β-catenin restrict GR-mediated transcriptional activation. A plasmid expressing LR RNA sequences that span open reading frame 2 (ORF2-Stop) inhibited GR-mediated transactivation of the BoHV-1 immediate early transcription unit 1 (IEtu1) and mouse mammary tumor virus (MMTV) promoter activity in mouse neuroblastoma cells (Neuro-2A). ORF2-Stop also reduced productive infection and GR steady-state protein levels in transfected Neuro-2A cells. Additional studies revealed that the constitutively active β-catenin mutant reduced the transactivation of the IEtu1 promoter by GR and dexamethasone. Collectively, these studies suggest ORF2 RNA sequences and Wnt/β-catenin signaling pathway actively promote maintenance of latency, in part, by impairing GR-mediated gene expression. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures

Figure 1

Review

Jump to: Research

34 pages, 1696 KiB

Open AccessReview

HSV-1 Cytoplasmic Envelopment and Egress

by Imran Ahmad and Duncan W. Wilson

Int. J. Mol. Sci. 2020, 21(17), 5969; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21175969 - 19 Aug 2020

Cited by 38 | Viewed by 10120

Abstract

Herpes simplex virus type 1 (HSV-1) is a structurally complex enveloped dsDNA virus that has evolved to replicate in human neurons and epithelia. Viral gene expression, DNA replication, capsid assembly, and genome packaging take place in the infected cell nucleus, which mature nucleocapsids exit by envelopment at the inner nuclear membrane then de-envelopment into the cytoplasm. Once in the cytoplasm, capsids travel along microtubules to reach, dock, and envelope at cytoplasmic organelles. This generates mature infectious HSV-1 particles that must then be sorted to the termini of sensory neurons, or to epithelial cell junctions, for spread to uninfected cells. The focus of this review is upon our current understanding of the viral and cellular molecular machinery that enables HSV-1 to travel within infected cells during egress and to manipulate cellular organelles to construct its envelope. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures

Figure 1

22 pages, 1091 KiB

Open AccessReview

Anterograde Neuronal Circuit Tracers Derived from Herpes Simplex Virus 1: Development, Application, and Perspectives

by Dong Li, Hong Yang, Feng Xiong, Xiangmin Xu, Wen-Bo Zeng, Fei Zhao and Min-Hua Luo

Int. J. Mol. Sci. 2020, 21(16), 5937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165937 - 18 Aug 2020

Cited by 6 | Viewed by 4714

Abstract

Herpes simplex virus type 1 (HSV-1) has great potential to be applied as a viral tool for gene delivery or oncolysis. The broad infection tropism of HSV-1 makes it a suitable tool for targeting many different cell types, and its 150 kb double-stranded DNA genome provides great capacity for exogenous genes. Moreover, the features of neuron infection and neuron-to-neuron spread also offer special value to neuroscience. HSV-1 strain H129, with its predominant anterograde transneuronal transmission, represents one of the most promising anterograde neuronal circuit tracers to map output neuronal pathways. Decades of development have greatly expanded the H129-derived anterograde tracing toolbox, including polysynaptic and monosynaptic tracers with various fluorescent protein labeling. These tracers have been applied to neuroanatomical studies, and have contributed to revealing multiple important neuronal circuits. However, current H129-derived tracers retain intrinsic drawbacks that limit their broad application, such as yet-to-be improved labeling intensity, potential nonspecific retrograde labeling, and high toxicity. The biological complexity of HSV-1 and its insufficiently characterized virological properties have caused difficulties in its improvement and optimization as a viral tool. In this review, we focus on the current H129-derived viral tracers and highlight strategies in which future technological development can advance its use as a tool. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures

Figure 1

31 pages, 2599 KiB

Open AccessReview

Herpes Simplex Virus Type 1 Interactions with the Interferon System

by Kevin Danastas, Monica Miranda-Saksena and Anthony L. Cunningham

Int. J. Mol. Sci. 2020, 21(14), 5150; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145150 - 21 Jul 2020

Cited by 44 | Viewed by 6028

Abstract

The interferon (IFN) system is one of the first lines of defense activated against invading viral pathogens. Upon secretion, IFNs activate a signaling cascade resulting in the production of several interferon stimulated genes (ISGs), which work to limit viral replication and establish an overall anti-viral state. Herpes simplex virus type 1 is a ubiquitous human pathogen that has evolved to downregulate the IFN response and establish lifelong latent infection in sensory neurons of the host. This review will focus on the mechanisms by which the host innate immune system detects invading HSV-1 virions, the subsequent IFN response generated to limit viral infection, and the evasion strategies developed by HSV-1 to evade the immune system and establish latency in the host. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures

Figure 1

19 pages, 1547 KiB

Open AccessReview

The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

by Raquel Bello-Morales, Sabina Andreu and José Antonio López-Guerrero

Int. J. Mol. Sci. 2020, 21(14), 5026; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145026 - 16 Jul 2020

Cited by 33 | Viewed by 8633

Abstract

Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous systems. After primary infection in epithelial cells, HSV-1 spreads retrogradely to the peripheral nervous system (PNS), where it establishes a latent infection in the trigeminal ganglia (TG). The virus can reactivate from the latent state, traveling anterogradely along the axon and replicating in the local surrounding tissue. Occasionally, HSV-1 may spread trans-synaptically from the TG to the brainstem, from where it may disseminate to higher areas of the central nervous system (CNS). It is not completely understood how HSV-1 reaches the CNS, although the most accepted idea is retrograde transport through the trigeminal or olfactory tracts. Once in the CNS, HSV-1 may induce demyelination, either as a direct trigger or as a risk factor, modulating processes such as remyelination, regulation of endogenous retroviruses, or molecular mimicry. In this review, we describe the current knowledge about the involvement of HSV-1 in demyelination, describing the pathways used by this herpesvirus to spread throughout the CNS and discussing the data that suggest its implication in demyelinating processes. Full article

(This article belongs to the Special Issue Herpes Simplex Virus: From Reactivation to Assembly)

► Show Figures