The only viral protein that is consistently expressed in these tumors is epsteinbarr nuclear antigen 1, which performs a variety of biological functions. Immunoinformatic and systems biology approaches to predict. Identification of the epstein barr virus portal sciencedirect. Epsteinbarr virus is a herpesvirus that causes infectious mononucleosis, carcinomas and immunoproliferative disease. 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. The epstein barr virus is a very common sickness that affects many people. Although the monoclonal proliferation of ebvinfected.
Its genome encodes 86 proteins, which provided targets for a structural genomics project. Aug 29, 2019 the epsteinbarr virus ebv is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Conservation of ebvsisrna sequence and secondary structure between ebv and other. Genomewide analysis of epsteinbarr virus ebv integration and strain in c6661 and raji cells. Epsteinbarr virus ebv is a ubiquitous herpes virus that infects most children during early childhood and causes few, if any, symptoms. Epsteinbarr virus stable intronicsequence rnas wikipedia. Ebv is a ubiquitous and persistent human pathogen, kept in check by the cytotoxic t cell response. Threedimensional structure of the epsteinbarr virus capsid. Like all herpesviruses, the epsteinbarr virus is relatively large and complex. Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Arceci, in lanzkowskys manual of pediatric hematology and oncology sixth edition, 2016. Ebv gh and gl form a multidomain structure similar to the recently determined hsv2 ghgl 28 and partial pseudorabies virus prv gh structures.
The role of viral proteins in epsteinbarr virus induced. 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. Epsteinbarr virus ebv, vitamin d, and smoking are among the most wellestablished environmental risk factors in ms. Atomic structure of the epsteinbarr virus portal nature. The gh and gl proteins associate to form a heterodimeric.
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. Efficient replication of epsteinbarr virus in stratified. Xiao k, yu z, li x, li x, tang k, tu c, qi p, liao q, chen p, zeng z, li g, xiong w. Ebv early genes are expressed independently of viral dna amplification, and several early gene. The epsteinbarr virus ebv is a doublestranded dna virus belonging to the herpesviridae family, which is divided into three subfamilies.
Genomewide analyses of epsteinbarr virus reveal conserved. 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. In the present study, we proved that six forms of barts were present in ebvpositive. 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. Epsteinbarr virusspecific humoral immune responses in health and disease article pdf available in current topics in microbiology and immunology 391. 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. Lymphocyte structure an overview sciencedirect topics. The epsteinbarr virus ebv, formally called human gammaherpesvirus 4, is one of the nine. Hv is a rare photodermatosis characterized by vesicles and crust formation. Especially epsteinbarr virus ebv infection has been shown to be highly associated with the development of sle, as presented in the following sections. 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. Epsteinbarr virus ebv is a ubiquitous herpes virus that infects most children. 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.
The structure of ebc is a icosahedral nucleocapsid. Nov 18, 2014 epsteinbarr virus establishes a lifelong latent infection i. The epsteinbarr virus ebv is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Ebv is a ubiquitous virus, so common that it has been difficult to. Ebv is the most common and most successful human virus. Threedimensional structure of the epsteinbarr virus capsid article pdf available in journal of general virology 93pt 8.
Infectious mononucleosis, which is caused by delayed primary ebv infection, increases the risk of developing ms. 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. Structure of a trimeric variant of the epsteinbarr virus. Epsteinbarr virus biological agents ncbi bookshelf. It is also associated with various nonmalignant, premalignant, and malignant epsteinbarr virusassociated lymphoproliferative diseases such as burkitt lymphoma, hemophagocytic lymphohistiocytosis, and hodgkins lymphoma. Previously, we published the individual crystal structures of ebv entry. 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. Well explore here what epstein barr is, what it does, and what it looks like. Epsteinbarr virus ebv, along with other members of the herpesvirus family, requires a set of viral glycoproteins to mediate host cell attachment and entry. Structural and mechanistic insights into the tropism of epsteinbarr.
Infection with ebv or cmv can cause an infectious mononucleosis syndrome of. Epsteinbarr virus establishes a lifelong latent infection i. Epsteinbarr virus ebv is a human herpesvirus implicated in cancer and autoimmune disorders. Epsteinbarr virus was first reported by british scientists m. The epsteinbarr virus ebv is a dna lymphotropic herpesvirus and the causative agent of infectious.
Pdf epsteinbarr virusspecific humoral immune responses in. Epstein barr virus human herpesvirus 4 or ebv is a member of the herpesvirdidae family. 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. Epsteinbarr virus ebv is an opportunistic human pathogen that causes a significant number of diseases in immunocompromised hosts. Despite its importance for human health, little structural information is available on ebv. Flemington a fascinating feature of epsteinbarr virus ebv is its ability to persist in the human host. 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. The chemical structure of ga was a subject of debate during the last decades. It is best known as the cause of infectious mononucleosis.
Ebv causes infectious mononucleosis, and ebvrelated malignancies, such as burkitts lymphoma bl, nasopharyngeal carcinoma npc, and ebvassociated gastric carcinoma ebvagc. Epsteinbarr virus ebv, whole genome sequencing, raji. Genomewide transcript structure resolution reveals. Viaggio twin doubledeck passenger coach ndw for sbb and szu viaggio twin low entrance doubledeck passenger coach barrierfree entrance, intelligent entrance system. Epsteinbarr virus ebv, a gammaherpesvirus, infects 90 % of the worlds population. Epsteinbarr virus snorna1 is a box cdsnorna generated by the virus during latency. Patients with caebv may present with cutaneous symptoms, including hypersensitivity to mosquito bites and hydroa vacciniforme hvlike eruptions.
Biology of epsteinbarr virus during infectious mononucleosis. Ebv and kaposis sarcoma herpesvirus kshv or hhv8 are the two human hostspecific viruses forming the. 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. The ebv virion structure is similar to other herpesviruses. Ebv occurs worldwide, affecting anyone at anypoint in their lifetime. Structural basis for epsteinbarr virus host cell tropism. 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. Structure of the active domain of the herpes simplex virus. Ebv is unique in that it infects about 95% of the adult population between 3540 years old in the u.
Jardetzkya,2,3 adepartment of biochemistry, molecular biology, and cell biology, northwestern university, 2205 tech drive, evanston, il 60208. Once infected the virus stays with the person for the rest of their life. Persistent latent infection with epsteinbarr virus contributes to tumorigenesis in a variety of cancer types. Structurebased design of smallmolecule inhibitors of. Structure of a trimeric variant of the epsteinbarr virus glycoprotein b marija backovica,1, richard longneckerb, and theodore s. Argentina does not have a centralised healthcare system. The role of epsteinbarr virus in multiple sclerosis.
The epsteinbarr virus ebvfigure 1 is a common human herpes virus that can cause both infectious mononucleosis and lymphoproliferative disease. Ebv noncoding rna binds nascent rna to drive host pax5. The structure consists of four domains, forming a flat, elongated shape, with individual domains sequentially folded along the length of the protein. Here the authors describe a highresolution atomic structure of the ebv. 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. Finally, gammaherpesvirinae, which include kaposis sarcomaassociated virus kshv and epsteinbarr virus ebv are associated with. 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. Finally, late lytic gene products tend to be proteins with structural roles, such as vca, which forms the viral capsid. In fact, it is estimated that more than 95% of adults are carriers of the virus. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. Aug 12, 2012 chronic active epsteinbarr virus ebv disease caebv is a systemic ebvpositive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Epsteinbarr virus transcribes chromatinized and subsequently. Ebv noncoding rna binds nascent rna to drive host pax5 to. After updating the annotation of the genome, 23 open reading frames were chosen for expression in escherichia coli, initially selecting.
Threedimensional structure of the epstein barr virus capsid article pdf available in journal of general virology 93pt 8. Geographic population structure in epsteinbarr virus. Structural requirements for c3d,gepsteinbarr virus. Structural requirements for c3d,gepsteinbarr virus receptor. Dec 28, 2010 the epsteinbarr virus ebv is a doublestranded dna virus belonging to the herpesviridae family, which is divided into three subfamilies. Diversity of epsteinbarr virus bamhia rightward transcripts. 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. Most commonly associated with infectious mononucleosis, much is still unknown about what effects the virus can have. 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. 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. Epsteinbarr virus infections and their association with human malignancies. Pdf threedimensional structure of the epsteinbarr virus.
Threedimensional structure of the epsteinbarr virus. An example of such structural analogs, which arise by means of divergent evolution from a single ancestor, include human il10 hil10. Complicating the annotation of transcript structures within these regions, empirical evidence from numerous studies has. There are two helical regions extending from residues 4 to 15 and from residues 22 to 32. Epsteinbarr virus ebv, is a human gammaherpesvirus that establishes lifelong infections in more than 95% of the human population. To date, however, little is known about the actual fulllength splicing form and its functions. Oct 02, 2015 the epsteinbarr virus ebv figure 1 is a common human herpes virus that can cause both infectious mononucleosis and lymphoproliferative disease. Synthesis, biosynthesis and biological activities of. 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. The epsteinbarr virus ebv, the first isolated human tumour virus, was identified in 1964 by. This study provides the first comprehensive genomewide survey of rna. Here we report the purification of the ebv capsid by cscl or sucrose density. The ubiquitous epsteinbarr virus ebv is associated with several human tumors, which include lymphoid and epithelial malignancies.
Aug 09, 20 epsteinbarr virus ebv is a human herpesvirus implicated in cancer and autoimmune disorders. Epsteinbarr virus ebv bamhia rightward transcripts barts. Epstein barr virus portals retain structural features found in other viral portals. It is best known as the cause of infectious mononucleosis mono or glandular fever. Recent research has led medicine to reason that it might be closely related to a number of forms of cancer. Despite structural similarities, each gb has a unique domain arrangement, demonstrating structural plasticity of gb that may accommodate virusspecific functional requirements. 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. The viruss structure consists of an envelope, spikes, a core, a capsid and a tegument. Population structure, pca and phenetic clustering of ebv genome sequences. Ebv infects both b lymphocytes and epithelial cells and causes. Ebv is implicated in the etiology of several different lymphoid and epithelial.
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. 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. 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. 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. 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. After ebers 1 and 2, ebvsisrna1 is the third most abundant ebv rna generated during a highly oncogenic form of virus latency latency iii. The epstein barr virus affects more individuals per year than you may know. Ebv may also contribute to ms pathogenesis indirectly by activating silent human endogenous retrovirusw. Primary infection by ebv can lead to infectious mononucleosis, and ebv persistence is associated with several malignancies. What is the structure of the national healthcare system, and how is it funded. Epsteinbarr virus epidemiology, serology, and genetic. Symptomatic infectious mononucleosis is relatively common in a seronegative individual especially during adolescence or young adulthood following exchange of saliva. 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. Genomewide transcript structure resolution reveals abundant.
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. Genomewide analysis of epsteinbarr virus ebv integration. 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. 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. Epsteinbarr virus stable intronicsequence rnas ebvsisrnas are a class of noncoding rnas generated by repeat introns in the epsteinbarr virus. Varies, but usually 47 weeks in adults and 12 weeks in children. Review article epsteinbarrvirusandsystemiclupuserythematosus. 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. B cells are the origin of more than 85% of ptld in organ transplant recipients. Alarmingly ebv can transform latently infected primary. Pdf epsteinbarr virusspecific humoral immune responses. Valacyclovir is the hydrochloride salt of the lvalyl ester of the antiviral drug acyclovir. Chronic active epsteinbarr virus ebv disease caebv is a systemic ebvpositive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly.
368 886 830 86 351 736 314 1063 1274 10 10 396 510 1058 1032 62 631 969 964 939 721 93 122 1147 1299 101 1213 1367 174 464 47 1338 1476 1220 886 1328 683