scholarly journals Characterization of heterosubunit complexes formed by the R1 and R2 subunits of herpes simplex virus 1 and equine herpes virus 4 ribonucleotide reductase

2000 ◽  
Vol 347 (1) ◽  
pp. 97-104
Author(s):  
Yunming SUN ◽  
Joe CONNER
Keyword(s):  
Enzyme Activity ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ribonucleotide Reductase ◽  
Herpes Virus ◽  
Subunit Interaction ◽  
Herpes Simplex Virus 1 ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Hsv 1

We report on the separate PCR cloning and subsequent expression and purification of the large (R1) and small (R2) subunits from equine herpes virus type 4 (EHV-4) ribonucleotide reductase. The EHV-4 R1 and R2 subunits reconstituted an active enzyme and their abilities to complement the R1 and R2 subunits from the closely related herpes simplex virus 1 (HSV-1) ribonucleotide reductase, with the use of subunit interaction and enzyme activity assays, were analysed. Both EHV-4 R1/HSV-1 R2 and HSV-1 R1/EHV-4 R2 were able to assemble heterosubunit complexes but, surprisingly, neither of these complexes was fully active in enzyme activity assays; the EHV-4 R1/HSV-1 R2 and HSV-1 R1/EHV-4 R2 enzymes had 50% and 5% of their respective wild-type activities. Site-directed mutagenesis was used to alter two non-conserved residues located within the highly conserved and functionally important C-termini of the EHV-4 and HSV-1 R1 proteins. Mutation of Pro-737 to Lys and Lys-1084 to Pro in EHV-4 and HSV-1 R1 respectively had no effects on subunit assembly. Mutation of Pro-737 to Lys in EHV-4 R1 decreased enzyme activity by 50%; replacement of Lys-1084 by Pro in HSV-1 R1 had no effect on enzyme activity. Both alterations failed to restore full enzyme activities to the heterosubunit enzymes. Therefore probably neither of these amino acids has a direct role in catalysis. However, mutation of the highly conserved Tyr-1111 to Phe in HSV-1 R1 inactivated enzyme activity without affecting subunit interaction.

scholarly journals Pathological processes of immunological decontamination of herpes simplex virus type 1 from the cornea

2020 ◽  
pp. 4-11
Author(s):  
Т.З. Керимов ◽  
В.П. Соболев ◽  
М.А. Соболева ◽  
Н.А. Гаврилова ◽  
С.А. Борзенок
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Herpes Virus ◽  
Toll Like Receptors ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Hsv 1

В обзоре представлено описание патофизиологических механизмов герпесвирусной инфекции. Согласно данным медицинской статистики, вирусом простого герпеса 1 типа инфицировано большинство населения планеты. В развивающихся странах данный вирус является ведущей инфекционной причиной поражения роговицы. Также вирусу простого герпеса 1 типа отводится роль одного из факторов, приводящих к отторжению трансплантата роговицы. Вышеописанные патологические явления сопряжены с перестройкой клеточных систем в ответ на вирусное воздействие. Недавние открытия в данной области обнаружили значительный вклад трансмембранных и эндосомальных Toll-подобных рецепторов во врожденный противовирусный клеточный ответ. Показано, что эндосомальные Toll-подобные рецепторы 3 типа экспрессируются в кератоцитах только после их фенотипического перехода в фибробласты. Данная трансформация обычно происходит в результате механических и патогенных воздействий на роговицу. Изменение рецепторного состава клеток в ответ на герпесвирусную инвазию вызывает выработку интерферонов 1 типа - интерферона-альфа, интерферона-бета, и синтезу провоспалительных цитокинов, что приводит к вирусной деконтаминации. This review describes pathophysiological mechanisms of herpes virus infection in cornea cells. It has been previously reported that herpes simplex virus type 1 (HSV-1) infects most of the world’s population. In developing countries, HSV-1 is the leading infectious cause of corneal damage. Also, herpes simplex virus type 1 was assigned the role of one of the factors leading to rejection of the corneal transplant. These pathological phenomena are associated with restructuring of cellular systems in response to viral exposure. Recent discoveries have revealed a significant contribution of transmembrane and endosomal Toll-like receptors to the innate antiviral cell response. It is well known that endosomal Toll-like receptors-3 are expressed in keratocytes only after their phenotypic transformation to fibroblasts. This transformation usually occurs as a result of mechanical or infectious impact on the cornea. Changes in the receptor composition of cells as a response to herpes virus invasion is the main cause of type 1 interferons (interferon-alpha and interferon-beta) production and expression of proinflammatory cytokines, which leads to viral decontamination.

scholarly journals An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Xu ◽  
Lei Tian ◽  
Jing Chen ◽  
Jing Wang ◽  
Rui Ma ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Herpes Virus ◽  
Innate Immune ◽  
Full Length ◽  
Herpes Simplex Virus 1 ◽  
Oncolytic Herpes Simplex Virus ◽  
Herpès Virus ◽  
Simplex Virus

AbstractOncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

scholarly journals Herpes Simplex Virus 1 Mutant with Point Mutations inUL39Is Impaired for Acute Viral Replication in Mice, Establishment of Latency, and Explant-Induced Reactivation

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Heba H. Mostafa ◽  
Thornton W. Thompson ◽  
Adam J. Konen ◽  
Steve D. Haenchen ◽  
Joshua G. Hilliard ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ribonucleotide Reductase ◽  
Large Subunit ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Protein Levels ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTIn the process of generating herpes simplex virus 1 (HSV-1) mutations in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations inUL39, which encodes the large subunit of ribonucleotide reductase, ICP6. These mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine (residue 950) substitutions in ICP6. To determine whether alteration of these amino acids was responsible for the KOS-NA phenotypesin vivo, we recombined the wild-type UL39 gene into the KOS-NA genome and rescued its acute replication phenotypes in mice. To further establish the role ofUL39in KOS-NA's decreased pathogenicity, theUL39mutations were recombined into HSV-1 (generating UL39mut), and this mutant virus showed reduced ocular and TG replication in mice comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data suggest that amino acid 950 of ICP6 likely plays an important role in ICP6 accumulation and inhibition of apoptosis, consequently impairing HSV-1 pathogenesis in a mouse model of HSV-1 infection.IMPORTANCEHSV-1 is a major human pathogen that infects ∼80% of the human population and can be life threatening to infected neonates or immunocompromised individuals. Effective therapies for treatment of recurrent HSV-1 infections are limited, which emphasizes a critical need to understand in greater detail the events that modulate HSV-1 replication and pathogenesis. In the current study, we identified a neuroattenuated HSV-1 mutant (i.e., KOS-NA) that contains novel mutations in the UL39 gene, which codes for the large subunit of ribonucleotide reductase (also known as ICP6). This mutant form of ICP6 was responsible for the attenuation of KOS-NAin vivoand resulted in diminished ICP6 protein levels and antiapoptotic effect. Thus, we have determined that subtle alteration of the UL39 gene regulates expression and functions of ICP6 and severely impacts HSV-1 pathogenesis, potentially making KOS-NA a promising vaccine candidate against HSV-1.

scholarly journals Herpes Virus, Oral Clinical Signs and QoL: Systematic Review of Recent Data

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 463 ◽  
Author(s):  
Salvatore Crimi ◽  
Luca Fiorillo ◽  
Alberto Bianchi ◽  
Cesare D’Amico ◽  
Giulia Amoroso ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Virus ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Herpes Simplex Virus 1 ◽  
Healing Phase ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2). Oral herpes virus is a very common and often debilitating infectious disease for patients, affecting oral health and having important psychological implications. The collection of relevant data comes from the scientific databases Pubmed, Embase; initially this collection obtained an extremely high number of results, 1415. After applying the inclusion and exclusion criteria, as well as a manual screening, the results included in this review were limited to 14. The results were expressed by evaluating all the signs and symptoms that this pathology entails during the study, paying attention to the characteristics linked to the quality of life and the psychological implications. This pathology has numerous therapies, which often make the healing phase of the manifestations of this viral pathology more comfortable. The therapies currently used for the treatment of this viral infection are pharmacological, topical, systemic, or instrumental, for example with laser devices.

Rezeptor «herpes virus entry mediator» moduliert in humanen Hornhaut-Epithelzellen die Produktion inflammatorischer Zytokine in Reaktion auf Stimulation mit HSV Typ 1

2016 ◽  
Vol 2 (1) ◽  
pp. 14-15
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Virus ◽  
Virus Entry ◽  
Herpes Virus Entry Mediator ◽  
Tnf Α ◽  
Ifn Γ ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Hsv 1

Ziele: Beurteilung der Rolle des «herpes virus entry mediator» (HVEM) beim Viruseintritt und der Produktion inflammatorischer Zytokine in Reaktion auf eine Stimulation mit dem Herpes-simplex-Virus Typ 1 (HSV-1) in humanen Hornhaut-Epithelzellen. Methoden: Die HVEM-Expression in humanen Hornhaut-Epithelzellen wurde mittels Immunfluoreszenz und Durchflusszytometrie bestimmt. Mit β-Galaktosidase-exprimierendem HSV-1 wurden die Hornhaut-Epithelzellen stimuliert, und Viruseintrittstests wurden durchgeführt, um den Eintritt von HSV-1 in die Zellen zu überprüfen. Die Konzentrationen der Zytokine TNF-α, IL-6, IFN-γ, IL-12 und IL-18 sowie der Chemokine MIP-1α, MIP-1β und MIP-2 in Reaktion auf die HSV-1-Stimulation wurden in mit Kontrollsubstanz oder HVEM-siRNA behandelten Hornhaut-Epithelzellen untersucht. Ergebnisse: Die humanen Hornhaut-Epithelzellen waren positiv für HVEM-Expression und zeigten eine hohe Suszeptibilität für den Eintritt von HSV-1. Ein HVEM-«Silencing» bewirkte keine wesentliche Veränderung des Viruseintritts. Allerdings wurden nach der HSV-1-Stimulation in den mit HVEM-siRNA behandelten Zellen im Vergleich zu den Kontrollzellen höhere Konzentrationen des Zytokins IFN-γ sowie der Chemokine MIP-1α und MIP-1β gemessen. Schlussfolgerungen: HVEM in menschlichen Hornhaut-Epithelzellen kann die Produktion bestimmter Zytokine und Chemokine dämpfen und dadurch die angeborene Immunreaktion gegen HSV-1 modulieren. Dies könnte ein bisher unbekannter Mechanismus in der Pathogenese der HSV-1-Infektion der Hornhaut sein. Übersetzung aus Ophthalmic Res 2015;54:128-134 (DOI: 10.1159/000437209)

scholarly journals Detection of Herpes Simplex Virus in Chronic Generalized Periodontitis via Polymerase Chain Reaction: A Pilot Study

2017 ◽  
Vol 9 (1) ◽  
pp. 7-11
Author(s):  
Thomas George Veliyaveetil
Keyword(s):  
Polymerase Chain Reaction ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Virus ◽  
Chain Reaction ◽  
Periodontal Destruction ◽  
Polymerase Chain ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Hsv 1

Background. As bacterial etiology could not support and explain various aspects of periodontal disease, herpes virus is now proposed to be one of the factors responsible for the periodontal destruction. The aim of the present study was to detect the presence of Herpes simplex virus (HSV) in patients with chronic generalized periodontitis. Methods. Eleven patients were consecutively selected for the study, of which 3 were diagnosed with moderate chronic generalized periodontitis and 8 with severe chronic generalized periodontitis. Subgingival material was taken from the deepest pocket of the dentition from every study subject, before the commencement of any procedure and polymerase chain reaction (PCR) assay was used to detect the presence of HSV-1 and -2. Results. HSV-1 and -2 DNA was not detected in any of the samples. Conclusion. This study is in contrast with previous studies and questions the proposed pathogenic role and clinical relevance of herpes virus in periodontitis.

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

1995 ◽  
Vol 53 ◽  
pp. 840-841
Author(s):  
Z. Hong Zhou ◽  
Jing He ◽  
Joanita Jakana ◽  
J. D. Tatman ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
3D Structure ◽  
Structure Study ◽  
Herpes Simplex Virus 1 ◽  
Shell Proteins ◽  
Life Threatening ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

Réactivations à herpès virus (HSV, CMV) en réanimation : qui et quand traiter ?

2019 ◽  
Vol 28 (3) ◽  
pp. 232-238
Author(s):  
C.-E. Luyt ◽  
G. Hékimian ◽  
N. Bréchot
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Virus ◽  
Herpès Virus ◽  
Simplex Virus ◽  
Charge Virale

Les réactivations à herpès simplex virus (HSV) et à cytomégalovirus (CMV) sont fréquentes chez le patient non immunodéprimé de réanimation. La réactivation HSV est localisée aux voies aériennes ; elle débute au niveau oropharyngé, progresse de façon descendante avec la contamination des voies aériennes distales et peut aboutir, chez certains malades, à une véritable bronchopneumonie herpétique. Elle est en outre associée à un pronostic défavorable. Le traitement prophylactique et préemptif des réactivations HSV ne peut pas être préconisé à l’heure actuelle. Le traitement curatif repose sur un avis d’experts, chez des malades présentant soit une charge virale élevée dans les voies aériennes distales, soit des signes cytologiques d’atteinte parenchymateuse pulmonaire sur les cellules recueillies lors du lavage bronchoalvéolaire. La réactivation CMV sanguine est fréquente et peut être isolée ou associée à une réactivation/atteinte pulmonaire et est aussi associée à un pronostic défavorable. Le traitement prophylactique de la réactivation CMV ne peut pas être préconisé, et le traitement préemptif est en cours d’évaluation. À l’heure actuelle, le traitement curatif des maladies pulmonaires à CMV repose soit sur des signes histologiques d’atteinte pulmonaire, soit sur un faisceau d’arguments clinicobiologiques évoquant une possible maladie à CMV.

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