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Viruses Apr 2022Randall Cohrs established the Colorado Alphaherpesvirus Latency Society (CALS) in 2011 [...].
Randall Cohrs established the Colorado Alphaherpesvirus Latency Society (CALS) in 2011 [...].
Topics: Alphaherpesvirinae; Colorado; Oncogenic Viruses
PubMed: 35632657
DOI: 10.3390/v14050915 -
Viruses Jun 2022Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most important infectious pathogens threatening the global pig industry. Like other... (Review)
Review
Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency.
Topics: Animals; Genome, Viral; Herpesvirus 1, Suid; Neurons; Pseudorabies; Swine; Virus Latency
PubMed: 35891367
DOI: 10.3390/v14071386 -
Current Issues in Molecular Biology 2021We are at an interesting time in the understanding of alpha herpesvirus latency and reactivation and their implications to human disease. Conceptual advances have come... (Review)
Review
We are at an interesting time in the understanding of alpha herpesvirus latency and reactivation and their implications to human disease. Conceptual advances have come from both animal and neuronal culture models. This review focuses on the concept that the tegument protein and viral transactivator VP16 plays a major role in the transition from latency to the lytic cycle. During acute infection, regulation of VP16 transactivation balances spread in the nervous system, establishment of latent infections and virulence. Reactivation is dependent on this transactivator to drive entry into the lytic cycle. In vivo de novo expression of VP16 protein is mediated by sequences conferring pre-immediate early transcription embedded in the normally leaky late promoter. In vitro, alternate mechanisms regulating VP16 expression in the context of latency have come from the SCG neuron culture model and include the concepts that (i) generalized transcriptional derepression of the viral genome and sequestration of VP16 in the cytoplasm for ~48 hours (Phase I) precedes and is required for VP16-dependent reactivation (Phase II); and (ii) a histone methyl/phospho switch during Phase I is required for Phase II reactivation. The challenge to the field is reconciling these data into a unified model of virus reactivation. The task of compiling this review was uncomfortably humbling, as if cataloging the stars in the universe. While not completely dark, our night sky is missing a multitude of studies which are among the many points of light contributing to our field. This article is a focused review in which we discuss from the vantage point of our expertise, just a handful of concepts that have or are emerging. A lookback at some of the pioneering work that grounds our field is also included.
Topics: Alphaherpesvirinae; Animals; Genome, Viral; Herpes Simplex; Herpes Simplex Virus Protein Vmw65; Humans; Latent Infection; Neurons; Simplexvirus; Transcription, Genetic; Virus Latency
PubMed: 32883886
DOI: 10.21775/cimb.041.267 -
Viruses Apr 2022Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in...
Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.
Topics: Biomarkers; DNA, Viral; Dermatitis; Epstein-Barr Virus Infections; Exanthema; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Space Flight; Virus Activation; Viruses; Viruses, Unclassified
PubMed: 35458519
DOI: 10.3390/v14040789 -
Viruses Oct 2023Herpesviruses are enveloped and have an amorphous protein layer surrounding the capsid, which is termed the tegument. Tegument proteins perform critical functions... (Review)
Review
Herpesviruses are enveloped and have an amorphous protein layer surrounding the capsid, which is termed the tegument. Tegument proteins perform critical functions throughout the viral life cycle. This review provides a comprehensive and comparative analysis of the roles of specific tegument proteins in capsid transport and virion morphogenesis of selected, well-studied prototypes of each of the three subfamilies of i.e., human herpesvirus-1/herpes simplex virus-1 (), human herpesvirus-5/cytomegalovirus () and human herpesvirus -8/Kaposi's sarcomavirus (). Most of the current knowledge is based on alpha herpesviruses, in particular HSV-1. While some tegument proteins are released into the cytoplasm after virus entry, several tegument proteins remain associated with the capsid and are responsible for transport to and docking at the nucleus. After replication and capsid formation, the capsid is enveloped at the nuclear membrane, which is referred to as primary envelopment, followed by de-envelopment and release into the cytoplasm. This requires involvement of at least three tegument proteins. Subsequently, multiple interactions between tegument proteins and capsid proteins, other tegument proteins and glycoproteins are required for assembly of the virus particles and envelopment at the Golgi, with certain tegument proteins acting as the central hub for these interactions. Some redundancy in these interactions ensures appropriate morphogenesis.
Topics: Humans; Capsid Proteins; Capsid; Virus Assembly; Herpesviridae; Herpesvirus 1, Human; Herpesvirus 8, Human; Morphogenesis; Virion; Viral Structural Proteins
PubMed: 37896835
DOI: 10.3390/v15102058 -
Viruses May 2022Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout...
Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is strongly associated with HSV recurrences in humans and animal models. However, the mechanisms through which stress hormones act on the latent virus to cause reactivation are unknown. We show that the stress hormones epinephrine (EPI) and corticosterone (CORT) induce HSV-1 reactivation selectively in sympathetic neurons, but not sensory or parasympathetic neurons. Activation of multiple adrenergic receptors is necessary for EPI-induced HSV-1 reactivation, while CORT requires the glucocorticoid receptor. In contrast, CORT, but not EPI, induces HSV-2 reactivation in both sensory and sympathetic neurons through either glucocorticoid or mineralocorticoid receptors. Reactivation is dependent on different transcription factors for EPI and CORT, and coincides with rapid changes in viral gene expression, although genes differ for HSV-1 and HSV-2, and temporal kinetics differ for EPI and CORT. Thus, stress-induced reactivation mechanisms are neuron-specific, stimulus-specific and virus-specific. These findings have implications for differences in HSV-1 and HSV-2 recurrent disease patterns and frequencies, as well as development of targeted, more effective antivirals that may act on different responses in different types of neurons.
Topics: Animals; Corticosterone; Epinephrine; Herpesvirus 1, Human; Herpesvirus 2, Human; Sensory Receptor Cells; Virus Latency
PubMed: 35632856
DOI: 10.3390/v14051115 -
Nature Communications Sep 2020Varicella-zoster virus (VZV), a member of the Alphaherpesvirinae subfamily, causes severe diseases in humans of all ages. The viral capsids play critical roles in...
Varicella-zoster virus (VZV), a member of the Alphaherpesvirinae subfamily, causes severe diseases in humans of all ages. The viral capsids play critical roles in herpesvirus infection, making them potential antiviral targets. Here, we present the 3.7-Å-resolution structure of the VZV A-capsid and define the molecular determinants underpinning the assembly of this complicated viral machinery. Overall, the VZV capsid has a similar architecture to that of other known herpesviruses. The major capsid protein (MCP) assembles into pentons and hexons, forming extensive intra- and inter-capsomer interaction networks that are further secured by the small capsid protein (SCP) and the heterotriplex. The structure reveals a pocket beneath the floor of MCP that could potentially be targeted by antiviral inhibitors. In addition, we identified two alphaherpesvirus-specific structural features in SCP and Tri1 proteins. These observations highlight the divergence of different herpesviruses and provide an important basis for developing antiviral drugs.
Topics: Capsid; Capsid Proteins; Cell Line; Cryoelectron Microscopy; Herpesvirus 3, Human; Humans; Models, Molecular; Protein Conformation; Protein Domains
PubMed: 32963252
DOI: 10.1038/s41467-020-18537-y -
Viruses Jan 2020Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a... (Review)
Review
Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.
Topics: Antiviral Agents; Biological Products; Drug Discovery; Drug Industry; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans
PubMed: 32013134
DOI: 10.3390/v12020154 -
Frontiers in Cellular and Infection... 2023Herpes simplex virus (HSV) is the most widely prevalent herpes virus worldwide, and the herpetic encephalitis and genital herpes caused by HSV infection have caused... (Review)
Review
Herpes simplex virus (HSV) is the most widely prevalent herpes virus worldwide, and the herpetic encephalitis and genital herpes caused by HSV infection have caused serious harm to human health all over the world. Although many anti-HSV drugs such as nucleoside analogues have been ap-proved for clinical use during the past few decades, important issues, such as drug resistance, toxicity, and high cost of drugs, remain unresolved. Recently, the studies on the anti-HSV activities of marine natural products, such as marine polysaccharides, marine peptides and microbial secondary metabolites are attracting more and more attention all over the world. This review discusses the recent progress in research on the anti-HSV activities of these natural compounds obtained from marine organisms, relating to their structural features and the structure-activity relationships. In addition, the recent findings on the different anti-HSV mechanisms and molecular targets of marine compounds and their potential for therapeutic application will also be summarized in detail.
Topics: Humans; Simplexvirus; Herpes Simplex; Structure-Activity Relationship
PubMed: 38259968
DOI: 10.3389/fcimb.2023.1302096 -
Viruses Sep 2022Herpes Simplex Virus 1 (HSV-1) is a neurotropic human virus that belongs to the subfamily of . Establishment of its productive infection and progression of disease... (Review)
Review
Herpes Simplex Virus 1 (HSV-1) is a neurotropic human virus that belongs to the subfamily of . Establishment of its productive infection and progression of disease pathologies depend largely on successful release of virions from the virus-producing cells. HSV-1 is known to exploit many host factors for its release. Recent studies have shown that heparanase (HPSE) is one such host enzyme that is recruited for this purpose. It is an endoglycosidase that cleaves heparan sulfate (HS) from the surface of infected cells. HS is a virus attachment coreceptor that is commonly found on cell surfaces as HS proteoglycans e.g., syndecan-1 (SDC-1). The current model suggests that HSV-1 during the late stage of infection upregulates HPSE, which in turn enhances viral release by removing the virus-trapping HS moieties. In addition to its role in directly enabling viral release, HPSE accelerates the shedding of HS-containing ectodomains of SDC-1, which enhances HSV-1 release via a similar mechanism by upregulating CREB3 and COPII proteins. This review outlines the role of HPSE and SDC-1 as newly assigned host factors that facilitate HSV-1 release during a lytic infection cycle.
Topics: Humans; Herpesvirus 1, Human; Syndecan-1; Glucuronidase; Heparitin Sulfate
PubMed: 36298711
DOI: 10.3390/v14102156