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Science Advances Jan 2020Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal....
Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.
Topics: Acyclovir; Animals; Antiviral Agents; Cyclodextrins; Female; Gold; Heparitin Sulfate; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Metal Nanoparticles; Mice; Simplexvirus; Virus Diseases; Zika Virus
PubMed: 32064341
DOI: 10.1126/sciadv.aax9318 -
Cell Host & Microbe Apr 2013Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central... (Review)
Review
Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central (CNS) nervous systems. The CNS is protected from most virus infections by effective immune responses and multilayer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections.
Topics: Alphaherpesvirinae; Animals; Central Nervous System; Herpesviridae Infections; Humans; Peripheral Nervous System; Virus Diseases
PubMed: 23601101
DOI: 10.1016/j.chom.2013.03.010 -
Viruses Nov 2020Alphaherpesviruses cause various diseases and establish life-long latent infections in humans and animals. These viruses encode multiple viral proteins and miRNAs to... (Review)
Review
Alphaherpesviruses cause various diseases and establish life-long latent infections in humans and animals. These viruses encode multiple viral proteins and miRNAs to evade the host immune response, including both innate and adaptive immunity. Alphaherpesviruses evolved highly advanced immune evasion strategies to be able to replicate efficiently in vivo and produce latent infections with recurrent outbreaks. This review describes the immune evasion strategies of alphaherpesviruses, especially against cytotoxic host immune responses. Considering these strategies, it is important to evaluate whether the immune evasion mechanisms in cell cultures are applicable to viral propagation and pathogenicity in vivo. This review focuses on cytotoxic T lymphocytes (CTLs), natural killer cells (NK cells), and natural killer T cells (NKT cells), which are representative immune cells that directly damage virus-infected cells. Since these immune cells recognize the ligands expressed on their target cells via specific activating and/or inhibitory receptors, alphaherpesviruses make several ligands that may be targets for immune evasion. In addition, alphaherpesviruses suppress the infiltration of CTLs by downregulating the expression of chemokines at infection sites in vivo. Elucidation of the alphaherpesvirus immune evasion mechanisms is essential for the development of new antiviral therapies and vaccines.
Topics: Alphaherpesvirinae; Animals; Antigen Presentation; Biomarkers; Cytokines; Herpesviridae Infections; Histocompatibility Antigens; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Cellular; Lymphocytes
PubMed: 33256093
DOI: 10.3390/v12121354 -
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 -
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 -
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 -
Current Opinion in Virology Aug 2013Human alphaherpesviruses (αHHV) - herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) - infect mucosal epithelial cells, establish a lifelong... (Review)
Review
Human alphaherpesviruses (αHHV) - herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) - infect mucosal epithelial cells, establish a lifelong latent infection of sensory neurons, and reactivate intermittingly to cause recrudescent disease. Although chronic αHHV infections co-exist with brisk T-cell responses, T-cell immune suppression is associated with worsened recurrent infection. Induction of αHHV-specific T-cell immunity is complex and results in poly-specific CD4 and CD8 T-cell responses in peripheral blood. Specific T-cells are localized to ganglia during the chronic phase of HSV infection and to several infected areas during recurrences, and persist long after viral clearance. These recent advances hold promise in the design of new vaccine candidates.
Topics: Alphaherpesvirinae; Animals; Herpesviridae Infections; Humans; Immunity, Cellular; T-Lymphocytes
PubMed: 23664660
DOI: 10.1016/j.coviro.2013.04.004 -
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 -
Viruses May 2024Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas...
Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas throughout the body. Vaccine strains used against MD include 3 (GaAHV3), a non-oncogenic chicken alphaherpesvirus homologous to MDV, and homologous meleagrid alphaherpesvirus 1 (MeAHV1) or turkey herpesvirus (HVT). Previous work has shown most of the MDV gC produced during in vitro passage is secreted into the media of infected cells although the predicted protein contains a transmembrane domain. We formerly identified two alternatively spliced gC mRNAs that are secreted during MDV replication in vitro, termed gC104 and gC145 based on the size of the intron removed for each (gC) transcript. Since gC is conserved within the subfamily, we hypothesized GaAHV3 (strain 301B/1) and HVT also secrete gC due to mRNA splicing. To address this, we collected media from 301B/1- and HVT-infected cell cultures and used Western blot analyses and determined that both 301B/1 and HVT produced secreted gC. Next, we extracted RNAs from 301B/1- and HVT-infected cell cultures and chicken feather follicle epithelial (FFE) skin cells. RT-PCR analyses confirmed one splicing variant for 301B/1 gC (gC104) and two variants for HVT gC (gC104 and gC145). Interestingly, the splicing between all three viruses was remarkably conserved. Further analysis of predicted and validated mRNA splicing donor, branch point (BP), and acceptor sites suggested single nucleotide polymorphisms (SNPs) within the 301B/1 transcript sequence resulted in no gC145 being produced. However, modification of the 301B/1 gC145 donor, BP, and acceptor sites to the MDV sequences did not result in gC145 mRNA splice variant, suggesting mRNA splicing is more complex than originally hypothesized. In all, our results show that mRNA splicing of avian herpesviruses is conserved and this information may be important in developing the next generation of MD vaccines or therapies to block transmission.
Topics: Animals; Chickens; RNA Splicing; Viral Envelope Proteins; RNA, Messenger; Marek Disease; Mardivirus; Viral Proteins; Herpesvirus 2, Gallid; Alternative Splicing; Antigens, Viral
PubMed: 38793663
DOI: 10.3390/v16050782 -
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