scholarly journals The crystal structure of the varicella zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity

2021 ◽  
Author(s):  
Johannes Schweininger ◽  
Mark Kriegel ◽  
Sigrun Häge ◽  
Marcus Conrad ◽  
Sewar Alkhashrom ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Present Report ◽  
Confocal Imaging ◽  
Interaction Patterns ◽  
Imaging Data ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Nuclear Egress ◽  
Computational Alanine Scanning ◽  
Functional Features

Varicella zoster virus (VZV) is a human pathogen from the α-subfamily of herpesviruses. Here, the crystal structure of the VZV Orf24-Orf27 complex is described, representing the essential viral core nuclear egress complex (NEC) that orchestrates the egress of the preassembled capsids from the nucleus. While previous studies have primarily emphasized the finding that the architecture of core NEC complexes is highly conserved among herpesviruses, the present report focusses on subfamily-specific structural and functional features that help explain the differences in the autologous versus nonautologous interaction patterns observed for NEC formation across herpesviruses. CoIP and confocal imaging data show that Orf24-Orf27 complex formation displays some promiscuity in a herpesvirus subfamily-restricted manner. At the same time, analysis of the NEC formation thermodynamic parameters of three prototypical α-, β- and γ-herpesviruses, i.e. VZV, human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) reveals highly similar binding affinities for the autologous interaction with some specific differences in the enthalpy and entropy terms. Computational alanine scanning and structural comparisons highlight intermolecular interactions shared among α-herpesviruses that are clearly distinct from those seen in β- and γ-herpesviruses. Combined, these data allow to explain the distinct properties of specificity and permissivity so far observed in herpesviral NEC interactions. These findings might prove highly valuable when attempting to target multiple herpesvirus core NECs with selective or broad-acting drug candidates.

scholarly journals Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 303 ◽  
Author(s):  
Sigrun Häge ◽  
Eric Sonntag ◽  
Eva Maria Borst ◽  
Pierre Tannig ◽  
Lisa Seyler ◽  
...  
Keyword(s):  
Confocal Imaging ◽  
Murine Cytomegalovirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Functional Complementarity ◽  
Nuclear Egress ◽  
Murine Fibroblasts ◽  
Epstein Barr

Nuclear egress is a regulated process shared by α-, β- and γ-herpesviruses. The core nuclear egress complex (NEC) is composed of the membrane-anchored protein homologs of human cytomegalovirus (HCMV) pUL50, murine cytomegalovirus (MCMV) pM50, Epstein–Barr virus (EBV) BFRF1 or varicella zoster virus (VZV) Orf24, which interact with the autologous NEC partners pUL53, pM53, BFLF2 or Orf27, respectively. Their recruitment of additional proteins leads to the assembly of a multicomponent NEC, coordinately regulating viral nucleocytoplasmic capsid egress. Here, the functionality of VZV, HCMV, MCMV and EBV core NECs was investigated by coimmunoprecipitation and confocal imaging analyses. Furthermore, a recombinant MCMV, harboring a replacement of ORF M50 by UL50, was analyzed both in vitro and in vivo. In essence, core NEC interactions were strictly limited to autologous NEC pairs and only included one measurable nonautologous interaction between the homologs of HCMV and MCMV. A comparative analysis of MCMV-WT versus MCMV-UL50-infected murine fibroblasts revealed almost identical phenotypes on the levels of protein and genomic replication kinetics. In infected BALB/c mice, virus spread to lung and other organs was found comparable between these viruses, thus stating functional complementarity. In conclusion, our study underlines that herpesviral core NEC proteins are functionally conserved regarding complementarity of core NEC interactions, which were found either virus-specific or restricted within subfamilies.

The Crystal Structure of the Epstein–Barr Virus Protease Shows Rearrangement of the Processed C Terminus

2002 ◽  
Vol 324 (1) ◽  
pp. 89-103 ◽  
Author(s):  
Marlyse Buisson ◽  
Jean-François Hernandez ◽  
David Lascoux ◽  
Guy Schoehn ◽  
Eric Forest ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
C Terminus ◽  
Epstein Barr

scholarly journals Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection

2021 ◽  
Vol 13 (1S) ◽  
pp. 21-26
Author(s):  
M. S. Gris ◽  
N. S. Baranova ◽  
N. N. Spirin ◽  
D. S. Kasatkin ◽  
D. V. Kiselev ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Presentation ◽  
Serum Levels ◽  
Main Group ◽  
Control Group ◽  
Herpesvirus Infection ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hsv 1

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p<0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p <0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

Cytomegaloviral Infections: Epidemiology, Therapy, and Prevention

1985 ◽  
Vol 7 (6) ◽  
pp. 169-175
Author(s):  
George A. Nankervis
Keyword(s):  
Giant Cells ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Current Review ◽  
New Concepts ◽  
The World ◽  
The Subject ◽  
Epstein Barr ◽  
Different Strains

The role of cytomegalovirus in human disease is a still-evolving story. Hanshaw presented an excellent review article on the subject in 1981 in this publication; this current review is an update, with particular emphasis on new concepts in the epidemiology and prevention of cytomegaloviral infection and disease. Historically, evidence of infection with cytomegalovirus was first reported by pathologists in many parts of the world. They noted the presence of giant cells with intranuclear inclusions while examining a diversity of organs microscopically. Isolation of the virus and development of serologic techniques eventually enabled a definitive study of the agent, its pathogenesis and epidemiology. Biologically, it is one of the herpesviruses and, as such, is a DNA virus. Other members of the group include varicella-zoster, herpes simplex, and Epstein-Barr virus. Several different strains of cytomegalovirus exist, and they have specific characteristics which are of interest. The virus is cell associated and tends to be very labile; it has a tendency to become latent and may possibly have malignant potential. EPIDEMIOLOGY Prevalence Infection with cytomegalovirus is found throughout the world. Studies of prevalence in a number of diverse populations have indicated that cytomegaloviral infection is ubiquitous. The major differences in prevalence between populations are related to the speed of acquisition of infection in various geographic and socioeconomic settings.

Select Viruses in Adults

2012 ◽  
pp. 61-79
Author(s):  
Randall C. Walker
Keyword(s):  
Viral Infections ◽  
Parvovirus B19 ◽  
Systemic Disease ◽  
Diagnostic Tools ◽  
Varicella Zoster ◽  
Epidemiologic Factors ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

The following types of viral infections are discussed in this chapter: viral infections that have the capacity for multiorgan or systemic disease; infections that affect adults who may be otherwise healthy or at least not in special populations such as herpes simplex virus (HSV) type 1, varicella-zoster virus (VZV), Epstein-Barr virus, adenovirus, mumps virus, human parvovirus B19, and coxsackievirus. Reviews of these viruses focus on differentiating clinical features, diagnostic tools and treatment, and salient microbiologic and epidemiologic factors.

scholarly journals An overview of viral infections of the nervous system in the immunosuppressed

2020 ◽  
Author(s):  
Peter G. E. Kennedy
Keyword(s):  
Nervous System ◽  
Measles Virus ◽  
Viral Infections ◽  
Jc Virus ◽  
Virus Infections ◽  
Inborn Errors ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

Abstract Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

scholarly journals Recent Developments in Viral Load Measurements in Human Herpesviruses

1999 ◽  
Vol 10 (suppl c) ◽  
pp. 33C-40C
Author(s):  
Guy Boivin
Keyword(s):  
Clinical Utility ◽  
Biological Fluids ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Herpesvirus ◽  
Relevant Information ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Recent Developments ◽  
Simplex Virus ◽  
Human Herpesviruses

Recent developments in molecular biology have allowed precise quantitative analysis of herpesvirus DNA in many biological fluids. Th is paper reviews the clinical utility of performing quantitative polymerase chain reaction testing for herpesviruses. In particular, the assessment of the cytomegalovirus (CMV) DNA load in blood with regard to the development of CMV disease in immunocompromised patients is discussed in greater detail. Relevant information exists to support measuring the CMV burden in the blood of AIDS and transplant patients for diagnostic and treatment monitoring purposes, and, to a lesser extent, to envision the monitoring of the circulating Epstein-Barr virus load for the prevention of pose-transplant lymphoproliferative disorders. On the ocher hand, there are controversial data on the clinical utility of measuring the herpes simplex virus (HSV) load in cerebrospinal fluid of patients with HSV encephalitis and on the relationship between the human herpesvirus 8 DNA load in diverse biological fluids and the presence of Kaposi's sarcoma. There is a paucity of information about the clinical impact of quantifying the other human herpesviruses (varicella-zoster virus, and human herpesviruses 6 and 7).

scholarly journals Association of infections with multiple sclerosis in Gulf Cooperation Council countries: a review

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051988415
Author(s):  
O Al Wutayd
Keyword(s):  
Multiple Sclerosis ◽  
Arabian Gulf ◽  
Human Herpesvirus ◽  
Epidemiological Studies ◽  
Gulf Cooperation Council ◽  
Gulf Region ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Serological Studies ◽  
Epstein Barr

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Infection can play a role in its etiology. Herein, a review is presented of studies that have reported an association between infection and MS risk in countries of the Arabian Gulf region. Searches of the PubMed, Google Scholar, and Science Direct databases were carried out using various search terms, and relevant studies published through January 2019 on the epidemiology of MS in Gulf Cooperation Council countries identified. MS has been found to be associated with measles in Saudi Arabia and Epstein–Barr virus in Kuwait whereas no association has been identified between risk of MS and varicella-zoster virus, mumps, or human herpesvirus-6. However, few epidemiological studies on this topic have been conducted in countries of the Gulf region. Longitudinal and serological studies to establish robust evidence between infection and risk of MS are highly recommended, and a regional MS registry is needed.

scholarly journals Amphipathic DNA Polymers Exhibit Antiherpetic Activity In Vitro and In Vivo

2008 ◽  
Vol 52 (8) ◽  
pp. 2727-2733 ◽  
Author(s):  
David I. Bernstein ◽  
Nathalie Goyette ◽  
Rhonda Cardin ◽  
Earl R. Kern ◽  
Guy Boivin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Parent Compound ◽  
Human Herpesvirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Acid Stable

ABSTRACT Phosphorothioated oligonucleotides have a sequence-independent antiviral activity as amphipathic polymers (APs). The activity of these agents against herpesvirus infections in vitro and in vivo was investigated. The previously established sequence-independent, phosphorothioation-dependent antiviral activity of APs was confirmed in vitro by showing that a variety of equivalently sized homo- and heteropolymeric AP sequences were similarly active against herpes simplex virus type 1 (HSV-1) infection in vitro compared to the 40mer degenerate parent compound (REP 9), while the absence of phosphorothioation resulted in the loss of antiviral activity. In addition, REP 9 demonstrated in vitro activity against a broad spectrum of other herpesviruses: HSV-2 (50% effective concentration [EC50], 0.02 to 0.06 μM), human cytomegalovirus (EC50, 0.02 to 0.13 μM), varicella zoster virus (EC50, <0.02 μM), Epstein-Barr virus (EC50, 14.7 μM) and human herpesvirus types 6A/B (EC50, 2.9 to 10.2 μM). The murine microbicide model of genital HSV-2 was then used to evaluate in vivo activity. REP 9 (275 mg/ml) protected 75% of animals from disease and infection when provided 5 or 30 min prior to vaginal challenge. When an acid-stable analog (REP 9C) was used, 75% of mice were protected when treated with 240 mg/ml 5 min prior to infection (P < 0.001), while a lower dose (100 mg/ml) protected 100% of the mice (P < 0.001). The acid stable REP 9C formulation also provided protection at 30 min (83%, P < 0.001) and 60 min (50%, P = 0.07) against disease. These observations suggest that APs may have microbicidal activity and potential as broad-spectrum antiherpetic agents and represent a novel class of agents that should be studied further.

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