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Current Issues in Molecular Biology 2021Alphaherpesvirus tegument assembly, secondary envelopment, and exocytosis processes are understood in broad strokes, but many of the individual steps in this pathway,...
Alphaherpesvirus tegument assembly, secondary envelopment, and exocytosis processes are understood in broad strokes, but many of the individual steps in this pathway, and their molecular and cell biological details, remain unclear. Viral tegument and membrane proteins form an extensive and robust protein interaction network, such that essentially any structural protein can be deleted, yet particles are still assembled, enveloped, and released from infected cells. We conceptually divide the tegument proteins into three groups: conserved inner and outer teguments that participate in nucleocapsid and membrane contacts, respectively; and 'middle' tegument proteins, consisting of some of the most abundant tegument proteins that serve as central hubs in the protein interaction network, yet which are unique to the alphaherpesviruses. We then discuss secondary envelopment, reviewing the tegument-membrane contacts and cellular factors that drive this process. We place this viral process in the context of cell biological processes, including the endocytic pathway, ESCRT machinery, autophagy, secretory pathway, intracellular transport, and exocytosis mechanisms. Finally, we speculate about potential relationships between cellular defenses against oligomerizing or aggregating membrane proteins and the envelopment and egress of viruses.
Topics: Alphaherpesvirinae; Autophagy; Biological Transport; Endosomal Sorting Complexes Required for Transport; Exocytosis; Host-Pathogen Interactions; Humans; Virus Assembly; Virus Physiological Phenomena; Virus Release
PubMed: 33622984
DOI: 10.21775/cimb.042.551 -
Current Opinion in Virology Aug 2015The H-1 parvovirus (H-1PV) exerts oncosuppressive action that has two components: oncotoxicity and immunostimulation. While many human tumor cells, including... (Review)
Review
The H-1 parvovirus (H-1PV) exerts oncosuppressive action that has two components: oncotoxicity and immunostimulation. While many human tumor cells, including conventional drug-resistant ones, can be killed by H-1PV, some fail to support progeny virus production, necessary for infection propagation in neoplastic tissues. This limitation can be overcome through forced selection of H-1PV variants capable of enhanced multiplication and spreading in human tumor cells. In the context of further developing H-1PV for use in cancer therapy, arming it with immunostimulatory CpG motifs under conditions preserving replication and oncolysis enhances its action as an anticancer vaccine adjuvant. A first clinical study of H-1PV treatment in glioma patients has yielded evidence of intratumoral synthesis of the viral oncotoxic protein NS1 and immune cell infiltration.
Topics: Alphaherpesvirinae; Animals; H-1 parvovirus; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 25841215
DOI: 10.1016/j.coviro.2015.03.008 -
Viruses Nov 2015In the nearly two decades since the popularization of green fluorescent protein (GFP), fluorescent protein-based methodologies have revolutionized molecular and cell... (Review)
Review
In the nearly two decades since the popularization of green fluorescent protein (GFP), fluorescent protein-based methodologies have revolutionized molecular and cell biology, allowing us to literally see biological processes as never before. Naturally, this revolution has extended to virology in general, and to the study of alpha herpesviruses in particular. In this review, we provide a compendium of reported fluorescent protein fusions to herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) structural proteins, discuss the underappreciated challenges of fluorescent protein-based approaches in the context of a replicating virus, and describe general strategies and best practices for creating new fluorescent fusions. We compare fluorescent protein methods to alternative approaches, and review two instructive examples of the caveats associated with fluorescent protein fusions, including describing several improved fluorescent capsid fusions in PRV. Finally, we present our future perspectives on the types of powerful experiments these tools now offer.
Topics: Alphaherpesvirinae; Biomedical Research; Host-Pathogen Interactions; Luminescent Proteins; Recombinant Fusion Proteins; Staining and Labeling; Virology
PubMed: 26610544
DOI: 10.3390/v7112915 -
Reviews in Medical Virology May 2018Herpesviruses (Herpesvirales) and tailed bacteriophages (Caudovirales) package their dsDNA genomes through an evolutionarily conserved mechanism. Much is known about the... (Review)
Review
Herpesviruses (Herpesvirales) and tailed bacteriophages (Caudovirales) package their dsDNA genomes through an evolutionarily conserved mechanism. Much is known about the biochemistry and structural biology of phage portal proteins and the DNA encapsidation (viral genome cleavage and packaging) process. Although not at the same level of detail, studies on HSV-1, CMV, VZV, and HHV-8 have revealed important information on the function and structure of herpesvirus portal proteins. During dsDNA phage and herpesviral genome replication, concatamers of viral dsDNA are cleaved into single length units by a virus-encoded terminase and packaged into preformed procapsids through a channel located at a single capsid vertex (portal). Oligomeric portals are formed by the interaction of identical portal protein monomers. Comparing portal protein primary aa sequences between phage and herpesviruses reveals little to no sequence similarity. In contrast, the secondary and tertiary structures of known portals are remarkable. In all cases, function is highly conserved in that portals are essential for DNA packaging and also play a role in releasing viral genomic DNA during infection. Preclinical studies have described small molecules that target the HSV-1 and VZV portals and prevent viral replication by inhibiting encapsidation. This review summarizes what is known concerning the structure and function of herpesvirus portal proteins primarily based on their conserved bacteriophage counterparts and the potential to develop novel portal-specific DNA encapsidation inhibitors.
Topics: Alphaherpesvirinae; Animals; Antiviral Agents; Capsid Proteins; Herpesviridae; Herpesviridae Infections; Humans; Models, Molecular; Protein Conformation; Protein Interaction Domains and Motifs; Protein Multimerization; Structure-Activity Relationship
PubMed: 29573302
DOI: 10.1002/rmv.1972 -
Advances in Experimental Medicine and... 2018Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in... (Review)
Review
Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene inborn errors of innate immunity have been shown to be associated with susceptibility to HSV encephalitis . Temporal lobe abnormalities revealed by magnetic resonance imaging-the most sensitive imaging method for HSV encephalitis-are considered strong evidence for the disease. Detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR) is the gold standard for the diagnosis of HSV encephalitis and neonatal meningoencephalitis. Intravenous acyclovir for 14-21 days is the standard treatment in HSV encephalitis. Neurological outcomes in neonates are improved by intravenous high-dose acyclovir for 21 days followed by oral acyclovir suppressive therapy for 6 months. Varicella-zoster virus (VZV) causes a wide range of CNS manifestations. VZV encephalitis typically occurs after primary infection, and reactivation of VZV may cause encephalitis. On the other hand, VZV infection of cerebral arteries produces vasculopathy, which can manifest as ischemic stroke. Vasculopathy can occur after primary infection or reactivation of VZV. PCR detection of VZV DNA in the cerebrospinal fluid can be used for the diagnosis of encephalitis or vasculopathy. Although there are no controlled treatment trials to assess VZV treatments of encephalitis or vasculopathy, intravenous acyclovir is a common treatment.
Topics: Alphaherpesvirinae; Animals; Antiviral Agents; Herpesviridae Infections; Humans; Nervous System Diseases
PubMed: 29896664
DOI: 10.1007/978-981-10-7230-7_5 -
Frontiers in Immunology 2019Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses... (Review)
Review
Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses have a protein-rich layer called the tegument that, connects the DNA-containing capsid to the envelope. Tegument proteins have a variety of functions, playing roles in viral entry, secondary envelopment, viral capsid nuclear transportation during infection, and immune evasion. Recently, many studies have made substantial breakthroughs in characterizing the innate immune evasion of tegument proteins. A wide range of antiviral tegument protein factors that control incoming infectious pathogens are induced by the type I interferon (IFN) signaling pathway and other innate immune responses. In this review, we discuss the immune evasion of tegument proteins with a focus on herpes simplex virus type I.
Topics: Alphaherpesvirinae; Animals; Herpesvirus 1, Human; Humans; Immune Evasion; Immunity, Innate; Signal Transduction; Viral Structural Proteins; Virus Internalization; Virus Replication
PubMed: 31572398
DOI: 10.3389/fimmu.2019.02196 -
Veterinary Journal (London, England :... Jan 2016Equid herpesvirus infections cause respiratory, neurological and reproductive syndromes. Despite preventive and control measures and the availability of vaccines and... (Review)
Review
Equid herpesvirus infections cause respiratory, neurological and reproductive syndromes. Despite preventive and control measures and the availability of vaccines and immunostimulants, herpesvirus infections still constitute a major threat to equine health and for the equine industry worldwide. Antiviral drugs, particularly nucleoside analogues and foscarnet, are successfully used for the treatment of human alphaherpesvirus infections. In equine medicine, the use of antiviral medications in alphaherpesvirus infections would decrease the excretion of virus and diminish the risk of contagion and the convalescent time in affected horses, and would also improve the clinical outcome of equine herpesvirus myeloencephalopathy. The combined use of antiviral compounds, along with vaccines, immune modulators, and effective preventive and control measures, might be beneficial in diminishing the negative impact of alphaherpesvirus infections in horses. The purpose of this review is to analyse the available information regarding the use of antiviral agents against alphaherpesviruses, with particular emphasis on equine alphaherpesvirus infections.
Topics: Alphaherpesvirinae; Animals; Antiviral Agents; Herpesviridae Infections; Herpesvirus 1, Equid; Horse Diseases; Horses; Humans
PubMed: 26654843
DOI: 10.1016/j.tvjl.2015.06.010 -
Journal of Clinical Virology : the... Aug 2023The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common...
BACKGROUND
The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge.
OBJECTIVE
The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites.
RESULTS
The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel.
CONCLUSION
The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses.
Topics: Humans; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Herpesvirus 6, Human; Virus Diseases; Viruses; Monkeypox virus
PubMed: 37364498
DOI: 10.1016/j.jcv.2023.105525 -
Dental and Medical Problems 2022Many complications can occur after the injection of local intraoral anesthetics (ILIA) before dental intervention. Facial paralysis (FP) is one of these complications.... (Review)
Review
Many complications can occur after the injection of local intraoral anesthetics (ILIA) before dental intervention. Facial paralysis (FP) is one of these complications. The purpose of this study was to systematically analyze the association between ILIA and FP. A systematic review was carried out taking into account the methodology of the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA statement. The search strategy used "Palsy AND Facial" and "Paralysis AND Facial" as search terms. The ScienceDirect, PubMed and Scopus databases were searched using the "dentistry journal" filter. The inclusion criteria included studies describing FP after or during ILIA that were published in dental journals. The CAse REports (CARE) checklist was applied in evaluating the methodological quality of case reports. A total of 2,462 articles (algorithm) were identified. After reviewing titles and abstracts, 18 articles were deemed relevant taking into account the objectives of this study. Only 13 of them, after reading the full text, met the inclusion criteria and were analyzed. Case reports on 18 cases of FP were analyzed, 12 of which described the early development of FP (onset within 24 h) and 6 the late development (onset after 24 h). Acceptable compliance with CARE guidelines was observed in the included studies . Early FP CRs presented the effect of the administered anesthetic on the facial nerve, and the vascular effect of the vasoconstrictor included in the anesthetic formula, while more recent FP CRs focused on the reactivation of herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6) or varicella-zoster virus (VZV).
Topics: Humans; Facial Paralysis; Herpesvirus 1, Human; Herpesvirus 3, Human; Face; Anesthetics
PubMed: 36583841
DOI: 10.17219/dmp/138910 -
Journal of Virology Mar 2023Type I interferon (IFN-I) response plays a prominent role in innate immunity, which is frequently modulated during viral infection. Here, we report DNA methylation...
Type I interferon (IFN-I) response plays a prominent role in innate immunity, which is frequently modulated during viral infection. Here, we report DNA methylation regulator UHRF1 as a potent negative regulator of IFN-I induction during alphaherpesvirus infection, whereas the viruses in turn regulates the transcriptional expression of UHRF1. Knockdown of UHRF1 in cells significantly increases interferon-β (IFN-β)-mediated gene transcription and viral inhibition against herpes simplex virus 1 (HSV1) and pseudorabies virus (PRV). Mechanistically, UHRF1 deficiency promotes IFN-I production by triggering dsRNA-sensing receptor RIG-I and activating IRF3 phosphorylation. Knockdown of UHRF1 in cells upregulates the accumulation of double-stranded RNA (dsRNA), including host endogenous retroviral sequence (ERV) transcripts, while the treatment of RNase III, known to specifically digest dsRNA, prevents IFN-β induction by siUHRF1. Furthermore, the double-knockdown assay of UHRF1 and DNA methyltransferase DNMT1 suggests that siUHRF1-mediated DNA demethylation may play an important role in dsRNA accumulation and subsequently IFN induction. These findings establish the essential role of UHRF1 in IFN-I-induced antiviral immunity and reveal UHRF1 as a potential antivrial target. Alphaherpesviruses can establish lifelong infections and cause many diseases in humans and animals, which rely partly on their interaction with IFN-mediated innate immune response. Using alphaherpesviruses PRV and HSV-1 as models, we identified an essential role of DNA methylation regulator UHRF1 in IFN-mediated immunity against virus replication, which unravels a novel mechanism employed by epigenetic factor to control IFN-mediated antiviral immune response and highlight UHRF1, which might be a potential target for antiviral drug development.
Topics: Animals; Humans; Antiviral Agents; CCAAT-Enhancer-Binding Proteins; Gene Expression; Herpesvirus 1, Human; Herpesvirus 1, Suid; Immunity, Innate; Interferon Regulatory Factor-3; Interferon Type I; Interferon-beta; Ubiquitin-Protein Ligases; Alphaherpesvirinae; Receptors, Immunologic
PubMed: 36916938
DOI: 10.1128/jvi.00134-23