Ebv early genes are expressed independently of viral dna amplification, and several early gene. In micellar solution of deuterated sodium dodecyl sulfate, the viral tap inhibitor adopts an ordered structure. Epsteinbarr virus ebv, a human gammaherpesvirus, was the first virus linked causally with a human tumour, following its identification in 1964 by epstein, barr and achong in a common childhood cancer in equatorial africa named after burkitt burkitts lymphoma or bl, who first described the malignancy. Pdf epsteinbarr virusspecific humoral immune responses in. Epsteinbarrvirusinfection ebv, also known as human herpesvirus 4 hhv4, is comprised of a 172 kb linear dsdna genome inside an envelopeenclosed icosahedral capsid figure 1. Population structure, pca and phenetic clustering of ebv genome sequences. Epstein barr virus human herpesvirus 4 or ebv is a member of the herpesvirdidae family. Posttransplant lymphoproliferative disorders ptld comprises a spectrum of pathologies ranging from early, ebv driven polyclonal proliferations resembling infectious mononucleosis to ebv positive or negative, monoclonal or polyclonal bcell or tcell lymphomas.
Ebv is a ubiquitous virus, so common that it has been difficult to. Viral glycoprotein b gb, a highly conserved glycoprotein within the herpesvirus family, is thought to be the viral fusogen based on structural comparison of ebv gb and herpes simplex virus hsv gb with the. Epsteinbarr virus ebv, also known as human herpesvirus 4 hhv4, is a member of the herpesviridae family and causes infectious mononucleosis, burkitts lymphoma, and nasopharyngeal carcinoma. Infectious mononucleosis, which is caused by delayed primary ebv infection, increases the risk of developing ms. Identification of the epstein barr virus portal sciencedirect. In fact, it is estimated that more than 95% of adults are carriers of the virus. Efficient replication of epsteinbarr virus in stratified. B cells are the origin of more than 85% of ptld in organ transplant recipients. Synthesis, biosynthesis and biological activities of.
Epsteinbarr virus biological agents ncbi bookshelf. It is known that ebv persistently infects the memory b cell pool of healthy individuals by activating growth and survival signaling pathways that can contribute to b cell lymphomagenesis. Patients with caebv may present with cutaneous symptoms, including hypersensitivity to mosquito bites and hydroa vacciniforme hvlike eruptions. Genomewide analyses of epsteinbarr virus reveal conserved. Atomic structure of the epsteinbarr virus portal nature.
Epsteinbarr virus ebv is an opportunistic human pathogen that causes a significant number of diseases in immunocompromised hosts. In this study, we investigated how three tcrs, which differ in their t cell immunodominance hierarchies and gene usage, interact with the same ebv determinant flrgraygl, bound to the same agpresenting molecule, hlab8. Pdf threedimensional structure of the epsteinbarr virus. Genomewide analysis of epsteinbarr virus ebv integration. Epsteinbarr virus was first reported by british scientists m. It is best known as the cause of infectious mononucleosis.
The ebv virion structure is similar to other herpesviruses. Epsteinbarr virus epidemiology, serology, and genetic. Ebv, like other herpesviruses, has three glycoproteins, glycoprotein b gb, gh, and gl, that form the core membrane fusion machinery mediating viral penetration into the cell. Epsteinbarr virus ebv bamhia rightward transcripts barts. Viaggio twin doubledeck passenger coach ndw for sbb and szu viaggio twin low entrance doubledeck passenger coach barrierfree entrance, intelligent entrance system. Epsteinbarr virus is a herpesvirus that causes infectious mononucleosis, carcinomas and immunoproliferative disease. Epsteinbarr virus establishes a lifelong latent infection i. Primary infection by ebv can lead to infectious mononucleosis, and ebv persistence is associated with several malignancies. The chemical structure of ga was a subject of debate during the last decades. Developing a habitat structure ebv using lidar imagery will use spaceborne lidar imagery from global ecosystem dynamics investigation gedi 25m diameter spatial resolution launched december 4, 2018 allows mapping of forest canopy heights, canopy threedimensional structure, aboveground biomass and surface topography. Vsnorna1 may act as a mirnalike precursor that is processed into 24 nucleotide sized rna fragments that target the 3utr of viral dna polymerase mrna. Its genome encodes 86 proteins, which provided targets for a structural genomics project. The epsteinbarr virus ebv, formally called human gammaherpesvirus 4, is one of the nine.
Structurebased design of smallmolecule inhibitors of. Recent research has led medicine to reason that it might be closely related to a number of forms of cancer. Here we report the purification of the ebv capsid by cscl or sucrose density. Epsteinbarr virus ebv, virus of the herpesviridae family that is the major cause of acute infectious mononucleosis, a common syndrome characterized by fever, sore throat, extreme fatigue, and swollen lymph glands. Ebv gh and gl form a multidomain structure similar to the recently determined hsv2 ghgl 28 and partial pseudorabies virus prv gh structures. The structure of hcmv gb resembles the postfusion structures of hsv1 and ebv homologs, establishing it as a new member of the class iii viral fusogens. Epsteinbarr virus ebv, whole genome sequencing, raji. The epsteinbarr virus ebv, the first isolated human tumour virus, was identified in 1964 by. Ebv may also contribute to ms pathogenesis indirectly by activating silent human endogenous retrovirusw. Valacyclovir is the hydrochloride salt of the lvalyl ester of the antiviral drug acyclovir.
Here the authors describe a highresolution atomic structure of the ebv. Structural requirements for c3d,gepsteinbarr virus. Epsteinbarr virus ebv, is the herpesvirus that causes infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons, including persons with aids. The role of viral proteins in epsteinbarr virus induced. Epsteinbarr virus ebv is a ubiquitous herpes virus that infects most children.
Ebv is a ubiquitous and persistent human pathogen, kept in check by the cytotoxic t cell response. Persistent latent infection with epsteinbarr virus contributes to tumorigenesis in a variety of cancer types. Threedimensional structure of the epsteinbarr virus capsid article pdf available in journal of general virology 93pt 8. Ebv and kaposis sarcoma herpesvirus kshv or hhv8 are the two human hostspecific viruses forming the. Structural requirements for c3d,gepsteinbarr virus receptor. Hv is a rare photodermatosis characterized by vesicles and crust formation. Ebv noncoding rna binds nascent rna to drive host pax5. Structure of the epstein barr virus major envelope glycoprotein gerda szakonyi1,2, michael g klein1, jonathan p hannan3, kendra a young3, runlin z ma4, rengasamy asokan3, v michael holers3.
Epsteinbarr virus epsteinbarr virus was discovered by examining electron micrographs of cells cultured from burkitts lymphoma, a childhood tumor that is common in areas of subsh afi h l i i d isaharan africa where malaria is endemic. Jan 24, 2019 epsteinbarr virus ebv, also known as human herpesvirus 4 hhv4, is a member of the herpesviridae family and causes infectious mononucleosis, burkitts lymphoma, and nasopharyngeal carcinoma. Oct 02, 2015 the epsteinbarr virus ebv figure 1 is a common human herpes virus that can cause both infectious mononucleosis and lymphoproliferative disease. Orally administered, valacyclovir is rapidly converted to acyclovir which inhibits viral dna replication after further conversion to the nucleotide analog acyclovir triphosphate by viral thymidine kinase, cellular guanyl cyclase, and a number of other cellular enzymes. There are two helical regions extending from residues 4 to 15 and from residues 22 to 32. Epsteinbarr virus epsteinbarr virus ebv, is the herpesvirus that causes infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons, including persons with aids. An example of such structural analogs, which arise by means of divergent evolution from a single ancestor, include human il10 hil10. Ebv is unique in that it infects about 95% of the adult population between 3540 years old in the u. Threedimensional structure of the epsteinbarr virus capsid.
Although the monoclonal proliferation of ebvinfected. Latestructural proteins include viral capsid proteins vca against which neutralising. Complicating the annotation of transcript structures within these regions, empirical evidence from numerous studies has. Structural and mechanistic insights into the tropism of epsteinbarr. Despite structural similarities, each gb has a unique domain arrangement, demonstrating structural plasticity of gb that may accommodate virusspecific functional requirements. Epsteinbarr virus an overview sciencedirect topics. Epsteinbarr virus ebv, a gammaherpesvirus, infects 90 % of the worlds population. Epsteinbarr virusspecific humoral immune responses in health and disease article pdf available in current topics in microbiology and immunology 391. The epstein barr virus is a very common sickness that affects many people. Epsteinbarr virus transmission from a blood donor to an organ transplant recipient with recovery of the same virus strain from the recipients blood and oropharynx. Aug 09, 20 epsteinbarr virus ebv is a human herpesvirus implicated in cancer and autoimmune disorders. The epsteinbarr virus ebv is a doublestranded dna virus belonging to the herpesviridae family, which is divided into three subfamilies. The structure consists of four domains, forming a flat, elongated shape, with individual domains sequentially folded along the length of the protein. Ebv noncoding rna binds nascent rna to drive host pax5 to.
Finally, gammaherpesvirinae, which include kaposis sarcomaassociated virus kshv and epsteinbarr virus ebv are associated with. Ebv infects both b lymphocytes and epithelial cells and causes. Epsteinbarr virus ebv, is a human gammaherpesvirus that establishes lifelong infections in more than 95% of the human population. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. Varies, but usually 47 weeks in adults and 12 weeks in children. What is the structure of the national healthcare system, and how is it funded. However, ebv is involved in several types of lymphomas and a subset about 9% of gastric carcinomas, although its specific role in gastric carcinogenesis remains unclear. It is also associated with various nonmalignant, premalignant, and malignant epsteinbarr virusassociated lymphoproliferative diseases such as burkitt lymphoma, hemophagocytic lymphohistiocytosis, and hodgkins lymphoma. The role of epsteinbarr virus in multiple sclerosis. Previously, we published the individual crystal structures of ebv entry. Threedimensional structure of the epstein barr virus capsid article pdf available in journal of general virology 93pt 8. The gh and gl proteins associate to form a heterodimeric. Genomewide transcript structure resolution reveals. The ubiquitous epsteinbarr virus ebv is associated with several human tumors, which include lymphoid and epithelial malignancies.
All these structures aid in making the virus successful in the infection process and as a means of avoiding detection from our bodys immune system. Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Dec 28, 2010 the epsteinbarr virus ebv is a doublestranded dna virus belonging to the herpesviridae family, which is divided into three subfamilies. Epsteinbarr virus ebv, along with other members of the herpesvirus family, requires a set of viral glycoproteins to mediate host cell attachment and entry. After ebers 1 and 2, ebvsisrna1 is the third most abundant ebv rna generated during a highly oncogenic form of virus latency latency iii. Especially epsteinbarr virus ebv infection has been shown to be highly associated with the development of sle, as presented in the following sections. The only viral protein that is consistently expressed in these tumors is epsteinbarr nuclear antigen 1, which performs a variety of biological functions. Ebv occurs worldwide, affecting anyone at anypoint in their lifetime. Viaggio twin doubledeck passenger coach ndw for sbb and szu viaggio twin low entrance doubledeck passenger coach barrierfree entrance, intelligent entrance system and spacious entrance area supporting quick. Flemington a fascinating feature of epsteinbarr virus ebv is its ability to persist in the human host. Biology of epsteinbarr virus during infectious mononucleosis. Epsteinbarr virus ebv is a ubiquitous herpes virus that infects most children during early childhood and causes few, if any, symptoms.
The epstein barr virus affects more individuals per year than you may know. Chronic active epsteinbarr virus ebv disease caebv is a systemic ebvpositive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Ebv but does eliminate crsmediated ebv infection and crosslinked csd,g internalization, overall, these studies sug gest an evolutionary role for the development of the repetitive scr structure in the rca family and demonstrate the critical role of the intracytoplasmic domain in cr2 function. After updating the annotation of the genome, 23 open reading frames were chosen for expression in escherichia coli, initially selecting. Pdf epsteinbarr virusspecific humoral immune responses. Like all herpesviruses, the epsteinbarr virus is relatively large and complex. Ebv is etiologically linked with the development of numerous b lymphocyte and epithelial cell malignancies, including burkitt, hodgkin, aidsassociated, and posttransplant lymphomas and nasopharyngeal carcinoma. This study provides the first comprehensive genomewide survey of rna.
Argentina does not have a centralised healthcare system. Genomewide transcript structure resolution reveals abundant. Epsteinbarr virus ebv is a human herpesvirus implicated in cancer and autoimmune disorders. The epsteinbarr virus ebvfigure 1 is a common human herpes virus that can cause both infectious mononucleosis and lymphoproliferative disease. To date, however, little is known about the actual fulllength splicing form and its functions. Threedimensional structure of the epsteinbarr virus. Arceci, in lanzkowskys manual of pediatric hematology and oncology sixth edition, 2016. Epsteinbarr virus infections and their association with human malignancies.
Symptomatic infectious mononucleosis is relatively common in a seronegative individual especially during adolescence or young adulthood following exchange of saliva. Jardetzkya,2,3 adepartment of biochemistry, molecular biology, and cell biology, northwestern university, 2205 tech drive, evanston, il 60208. Structure of a trimeric variant of the epsteinbarr virus. Infection with ebv or cmv can cause an infectious mononucleosis syndrome of. Immunoinformatic and systems biology approaches to predict. A barplot displaying the probability of provenance as inferred by structure for all the 127 ebv genomes considered in this study, geographic origins are shown for each isolate. Aug 12, 2012 chronic active epsteinbarr virus ebv disease caebv is a systemic ebvpositive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Ebv is the most common and most successful human virus. The epsteinbarr virus ebv, formally called human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. Epsteinbarr virus stable intronicsequence rnas wikipedia. The epsteinbarr virus, formally called human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. Conservation of ebvsisrna sequence and secondary structure between ebv and other.
Structural basis for epsteinbarr virus host cell tropism. The structure of ebc is a icosahedral nucleocapsid. The epsteinbarr virus ebv is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Aug 29, 2019 the epsteinbarr virus ebv is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Epsteinbarr virus stable intronicsequence rnas ebvsisrnas are a class of noncoding rnas generated by repeat introns in the epsteinbarr virus. Nov 18, 2014 epsteinbarr virus establishes a lifelong latent infection i. Structure of the active domain of the herpes simplex virus. Well explore here what epstein barr is, what it does, and what it looks like. It is best known as the cause of infectious mononucleosis mono or glandular fever. Epsteinbarr virus transcribes chromatinized and subsequently. Geographic population structure in epsteinbarr virus. The epsteinbarr virus ebv is a dna lymphotropic herpesvirus and the causative agent of infectious.
Diversity of epsteinbarr virus bamhia rightward transcripts. Pax5 has further been shown to regulate ebv latent gene expression,asdepletionofpax5results,forexample,inupregulation of the expression of lmp1, the main transforming protein of ebv that acts as a classical oncogene, and of both lmp2 isoforms arvey et al. Structure of a trimeric variant of the epsteinbarr virus glycoprotein b marija backovica,1, richard longneckerb, and theodore s. Once infected the virus stays with the person for the rest of their life.
Epsteinbarr virus snorna1 is a box cdsnorna generated by the virus during latency. Some data must be provided by countries themselves, whereas a wealth of additional supporting information is available from elsewhere to support national and global monitoring efforts. Despite its importance for human health, little structural information is available on ebv. Ebv for invasion monitoring there is a key set of measurements, or essential variables, that are needed to monitor biological invasions. Ebv causes infectious mononucleosis, and ebvrelated malignancies, such as burkitts lymphoma bl, nasopharyngeal carcinoma npc, and ebvassociated gastric carcinoma ebvagc. Alarmingly ebv can transform latently infected primary. Most commonly associated with infectious mononucleosis, much is still unknown about what effects the virus can have.
A specific group of latencyassociated proteins is expressed in bcell and epithelial malignancies and likely contributes to tumorigenesis, but the role of epithelial cells in the virus life cycle is not well understood. Little is known concerning the roles of rna structure in this important human pathogen. Xiao k, yu z, li x, li x, tang k, tu c, qi p, liao q, chen p, zeng z, li g, xiong w. Epstein barr virus portals retain structural features found in other viral portals. Here the authors describe a highresolution atomic structure of the ebv portal, which serves as the entrance and exit pore for the viral genome and is a potential pharmacological target for the. Ebv is implicated in the etiology of several different lymphoid and epithelial. The viruss structure consists of an envelope, spikes, a core, a capsid and a tegument. Review article epsteinbarrvirusandsystemiclupuserythematosus.
1494 821 439 1567 669 472 1297 392 1591 605 292 1102 596 1176 637 1424 422 328 172 292 1444 172 936 1383 685 1161 1485 1031 393 542 1493 1530 89 557 638 555 993 47 233 1388 319 715 686 1261 840