Viral pathogens have not been much explored, but recent interest has focused on epsteinbarr virus ebv. Epsteinbarr virus lytic reactivation regulation and its. Association between human papillomavirus and epstein barr virus infections in human oral carcinogenesis. Association between human papillomavirus and epsteinbarr virus infections in human oral carcinogenesis. Fifty eight randomly selected cases of squamous cell carcinomas scc of the uterine cervix, 14 normal cervices specimens, 21 cin23. Epsteinbarr virus ebv is a ubiquitous herpes virus that infects most children during early childhood and causes few, if any, symptoms. Pdf the epsteinbarr virus ebv is the first herpesvirus identified to be. Role of the epsteinbarr virus zebra protein and hpv in. Role of the epsteinbarr virus zebra protein and hpv in the. Thus, whilst there is good evidence to suggest that ebv is a human carcinogen, its precise roles in the development of virusassociated human tumours requires. The epsteinbarr virus was named after michael anthony epstein born 18 may 1921, now a professor emeritus at the university of bristol, and yvonne barr 19322016, a 1966 ph. Ebv associated burkitts lymphoma ebl is endemic in children living in subsaharan africa. Although it is thought that ebv latency participates in the development of npc, increasing evidence reveals that the lytic cycle also plays an important role in the carcinogenic process. Nonetheless, the ebv is the causative agent of infectious.
Epstein barr virus can be cultured in lyphoblastoid cell lines. Anderson cancer center, houston, texas abstract ebv was the first human virus to be directly implicated in carcinogenesis. Despite the fact that the implication of human papillomavirus hpv in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a coinfection with high risk hpv hrhpv and epstein barr virus ebv is still not fully understood. Ebvassociated malignancies are associated with a latent form of infection, and several of the ebvencoded latent proteins are known to mediate cellular transformation. Epsteinbarr virus and virus human protein interaction maps proc natl acad sci usa 2007. Oct 23, 2009 epsteinbarr virus ebv infection alone cannot drive normal cells towards carcinoma development. Epstein barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis hongde li 1,2,3, sufang liu4, jianmin hu, xiangjian luo1,2,3, namei li1,2,3, ann m. These include six nuclear antigens and three latent membrane proteins. Epsteinbarr virus ebv is an etiological agent of npc, but how it contributes to carcinogenesis is not completely clear. Pdf role of the epsteinbarr virus zebra protein and hpv. Approximately 95% of the worlds population sustain an asymptomatic lifelong ebv infection. Thompson and razelle kurzrock department of bioimmunotherapy, university of texas, m.
It is possible that ebv infection of normal differentiating epithelial cells results in virus replication, whereas, in epithelial cells that are. Epsteinbarr virus and microsatellite instability in. Normal host populations can have vastly different susceptibility to ebvrelated tumors as demonstrated by geographical and. Ebv is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including bcell lymphomas burkitt lymphoma, hodgkin lymphoma, and posttransplant lymphoproliferative disorder, various tcellnk. Epsteinbarr virus ebv is the causative agent of infectious mononucleosis and a potent transforming agent for human blymphocytes in vitro. Introduction eepsteinbarrvirusebvwasthe rstdiscoveredhuman. Liver tissue 115 hcc patients and 26 noncarcinoma patients were studied. Three adult patients with chronic active epsteinbarr virus infeciton caebv had high antiebvvca antibody, positive antiea, low antiebna and were associated with systemic lymphadenopathies and immunosuppression. Role of viral mirnas and epigenetic modifications in epstein. Epsteinbarr virus ebv infection is found in a subset of gastric cancers. Epstein barr virus was first reported by british scientists m.
Epsteinbarr virus infection as an epigenetic driver of. Epstein barr virus belongs to genus lymphocryptovirus of the subfamily gammaherpesvirinae in the herpesviridae family 1,2. Ebv is associated with a variety of diseases including infectious mononucleosis, hairy leukoplakia, inflammatory pseudotumors, nasopharyngeal carcinoma npc, burkitts lymphoma, hodgkin lymphoma, posttransplant lymphoproliferative disorders, hiv. Frontiers epsteinbarr virusassociated malignancies. Ebv persists in the memory b cell pool of normal healthy individuals and any disruption of this interaction results in virusassociated b cell tumours. Human papillomavirus and epsteinbarr virus coinfection. Ebv infection was examined using polymerase chain reaction pcr with two different primer pairs flanking the bam hi w fragment of ebv and by ebvencoded small rnas eber in situ hybridization in various histologic types of cervical cancer, including 17 cases of squamous. Epsteinbarr virus cas no none assigned known to be a human carcinogen also known as ebv or human herpesvirus 4 hhv4 carcinogenicity epsteinbarr virus ebv is known to be a human carcinogen based on sufficient evidence from studies in humans. The virus has been implicated in the development of several malignancies, including endemic burkitts lymphoma, nasopharyngeal carcinoma, hodgkins lymphomas, t cell lymphomas and gastric adenocarcinomas 1, 2.
The role of viral proteins in epsteinbarr virus induced. To determine at what stage during gastric carcinogenesis epsteinbarr virus ebv enters the gastric epithelial cells, the presence of ebv was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomachgastric carcinoma of the intact stomach gcis and gastric stump carcinoma gscand their presumed precursor lesions. 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. The epsteinbarr virus ebv is impli catedinmanyneoplasticdiseases,nota bly lymphomas and epithelial cancers. Key words epsteinbarr virus latent membrane protein 1 posttransplant lymphoproliferative. Studies of an association of this ubiquitous herpesvirus with breast cancer have had notably inconsistent. Role of viral mirnas and epigenetic modifications in. An update on epsteinbarr virus and nasopharyngeal carcinogenesis. The epstein barr virus ebv is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated.
Epsteinbarr virus lytic reactivation regulation and its pathogenic role in carcinogenesis hongde li 1,2,3, sufang liu4, jianmin hu, xiangjian luo1,2,3, namei li1,2,3, ann m. Identification of genomic alterations in nasopharyngeal. This conclusion is based on evidence from epidemiological, clinical, and molecular. Epsteinbarr virus, malaria and endemic burkitt lymphoma. Also, ebv is the first human virus to be directly implicated in carcinogenesis. The epsteinbarr virus ebv is the first herpesvirus identified to be associated. Viral carcinogenesis beyond malignant transformation. Specifically, ebv is ubiquitous member of the human gammaherpesvirus family that causes mononucleosis during acute and lytic infection and also establishes a persistent and. Epsteinbarr is responsible for mystery illnesses of every category. An update on epsteinbarr virus and nasopharyngeal carcinogenesis article in head and neck pathology 12.
Although most humans coexist with the virus without serious sequelae, a small proportion will develop tumors. However, the molecular basis of npc remains largely unknown, and the role of ebv genomic variations in the pathogenesis of npc is unclear. Epstein barr virus ebv is the causative agent of infectious mononucleosis, and it may also be found in a wide variety of benign and malignant lesions including oral hairy leukoplakia. Epstein barr 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. In spite of these findings, the importance of ebv in gastric carcinogenesis has long been underestimated. As the etiology and progression of breast cancer remain incompletely understood, novel routes of disease pathogenesis are important to consider. Epsteinbarr virus lytic reactivation regulation and its pathogenic role in carcinogenesis. Recently this hypothesis has been addressed because of studies on the contribution of the epsteinbarr virus ebv to the aggressiveness of nasopharyngeal carcinoma npc. Pdf role of the epsteinbarr virus zebra protein and hpv in. Hongde li 1,2,3, sufang liu 4, jianmin hu 1,2,3, xiangjian luo 1,2,3, namei li 1,2,3, ann m. The epsteinbarr virus is known to be able to infect only two different types of cells in the body.
Epsteinbarr virus lytic infection contributes to lymphoproliferative disease in a scid mouse model. Ebv encodes a large number of micrornas, which actively participate in the. Epstein barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis. Its also called the kissing disease because of one way you can spread it to. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of east asia and the burkitt lymphoma which predominantly occurs in parts of africa and new guinea. The epsteinbarr virus ebv is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. Roles of traf2 and traf3 in epsteinbarr virus latent membrane protein 1induced alternative nfkappab activation. Ebv is associated with a variety of diseases including infectious mononucleosis, hairy leukoplakia, inflammatory pseudotumors, nasopharyngeal carcinoma npc, burkitts lymphoma, hodgkin lymphoma, posttransplant lymphoproliferative disorders, hivassociated bcell. The latency programs adopted by the virus in b cells are different from those in epithelial cells and for each type of latency, a distinct set of viral proteins and transcripts will be produced 82 calderwood ma, venkatesan k, xing l, et al.
In recent years, studies have suggested that epsteinbarr virus ebv is associated with hcc. D graduate from the university of london, who together discovered and, in 1964, published on the existence of the virus. Review article role of viral mirnas and epigenetic. Fifty eight randomly selected cases of squamous cell carcinomas scc of the uterine cervix, 14 normal.
Beyond burkitts lymphoma subsequent to its discovery over 45 years ago, epsteinbarr virus. Review epsteinbarr virus lytic reactivation regulation. Ebv infection was examined using polymerase chain reaction pcr with two different primer pairs flanking the bam hi w fragment of ebv and by ebvencoded small rnas eber in situ hybridization in various histologic types of cervical cancer. In recent years, studies have suggested that epstein barr virus ebv is associated with hcc although opposite results have been subsequently reported. Taken together, these data suggest that, unlike ebv associated b cell tumours, where the virus is considered to be an initiating factor in the oncogenic process, virus infection in the context of npc pathogenesis behaves as a tumourpromoting agent. To determine at what stage during gastric carcinogenesis epsteinbarr virus ebv enters the gastric epithelial cells, the presence of ebv was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomachgastric carcinoma of the intact stomach gcis and gastric stump carcinoma gscand their. The case 1 and 2 had elevated serum immunoglobulin levels, and recurrent infections, and case 3 showed pancytopenia. The present study was to determine the prevalence of ebv in hcc patients, and whether ebv acted synergistically with hepatitis viruses in hcc carcinogenesis. Immunodeficiency and carcinogenesis in patients with. In some people, the latent virus is capable of causing malignant tumours, such as nasopharyngeal carcinoma and various b and tcell lymphomas, at sites including the head, neck and oropharyngeal region. Epsteinbarr virus ebv latent gene expression in nasopharyngeal carcinoma npc.
Studies of an association of this ubiquitous herpesvirus with breast cancer have had notably inconsistent results, marked by varying ebv presence. Plasmodium falciparum, the causative agent of severe malaria, is itself not considered a carcinogenic organism. It consists of a doublestranded 172 kb dna genome, enclosed within an icosahedral capsid, surrounded by a phospholipid rich envelope 1,3. Epsteinbarr virus and cancer clinical cancer research. Ebv is associated with a variety of diseases including infectious mononucleosis, hairy leukoplakia, inflammatory pseudotumors, nasopharyngeal carcinoma npc, burkitts lymphoma, hodgkin lymphoma, posttransplant. Dec 01, 2004 in recent years, studies have suggested that epstein barr virus ebv is associated with hcc although opposite results have been subsequently reported.
Epsteinbarr virus in hepatocellular carcinogenesis europe. Epsteinbarr virus belongs to genus lymphocryptovirus of the subfamily gammaherpesvirinae in the herpesviridae family 1,2. However, the occurrence of endemic burkitt lymphoma ebl. We examined whether epsteinbarr virus ebv infection plays a role in cervical carcinogenesis in korean women. To satisfy demand for more building parts, host cells will chew up their. Epsteinbarr virus in gastric carcinomas and gastric stump. Epsteinbarr virus ebv establishes latent infection and is associated with tumors, such as burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancers. Review epsteinbarr virus lytic reactivation regulation and. It is thought that loss of heterozygosity loh, possibly as a result of inherited traits chinese ethnicity as well as exposure to dietary factors salted fish and other environmental cofactors, is an early stage event in the pathogenesis of. The present study was to determine the prevalence of ebv in hepatocellular carcinoma hcc patients, and whether ebv acted synergistically with hepatitis viruses in hcc carcinogenesis. Pdf association between human papillomavirus and epstein. Although epsteinbarr virus ebv infection is widely distributed, certain ebv driven malignancies are geographically restricted. Shah cancer research uk institute for cancer studies, school of cancer sciences, university of birmingham, edgbaston, birmingham, uk.
Epsteinbarr is the virus that causes mononucleosis. Nasopharyngeal carcinoma npc is a common tumor in southern china with marked ethnic and geographic distributions and concomitant epsteinbarr virus ebv infection. Epsteinbarr virus infection and human malignancies ncbi. Approximately 95% of the worlds population sustain an asymptomatic life. Achong, who found viruslike particles in cells grown from tissues involved with a newly described lymphatic cancer. The virus has been implicated in the development of several malignancies, including endemic burkitts lymphoma, nasopharyngeal carcinoma, hodgkins lymphomas, t cell lymphomas and gastric. Epsteinbarr virusassociated gastric cancer ebvagc accounts for about 10% of all gastric cancer cases and has unique pathological and molecular characteristics. The epsteinbarr virus ebv has created a secret epidemic. Epsteinbarr virus can be cultured in lyphoblastoid cell lines. Role of the epstein barr virus zebra protein and hpv in the carcinogenesis of nasopharyngeal carcinoma. Human papillomavirus and epsteinbarr virus coinfection in. Ebv was the first human virus to be directly implicated in carcinogenesis.
These include six nuclear antigens and three latent. Liver cancer epsteinbarr virus in hepatocellular carcinogenesis. Despite the fact that the implication of human papillomavirus hpv in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a coinfection with high risk hpv hrhpv and epsteinbarr virus ebv is still not fully understood. Epsteinbarr virus in gastric carcinomas and gastric stump carcinomas. Epstein barr virus an overview sciencedirect topics. The epsteinbarr virus ebv was the first discovered human tumorcausing virus considered as the etiologic agent of burkitts lymphoma bl, an unusual african pediatric lymphoma. Epsteinbarr virus ebv belongs to the group of gammaherpes viruses and was the first recognized human oncovirus. Ebv is unique in that it infects about 95% of the adult population between 3540 years old in the u. Key laboratory of carcinogenesis and invasion, chinese ministry of education, xiangya hospital, central south university, changsha.
Although the precise role of ebv in the carcinogenic process is currently poorly understood, the presence of the virus in all tumour cells provides opportunities. This population is heavily exposed to food contaminated with the mycotoxin aflatoxin b1 afb1. The epsteinbarr virus ebv is the first herpesvirus identified to be associated with human cancers known to infect the majority of the world population. Normal host populations can have vastly different susceptibility to ebv related tumors as demonstrated by geographical and immunological variations in the prevalence. Ebv is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including bcell lymphomas burkitt lymphoma, hodgkin lymphoma, and posttransplant lymphoproliferative disorder, various tcellnk lymphoproliferative disorders, nasopharyngeal. You might know this disease better by its nickname, mono. Update on epsteinbarr virus and gastric cancer spandidos. For some people, it creates fatigue and pain that go unnamed. In recent years, studies have suggested that epstein barr virus ebv is associated with hcc. Epsteinbarr virus in hepatocellular carcinogenesis.
The epstein barr virus ebvfigure 1 is a common human herpes virus that can cause both infectious mononucleosis and lymphoproliferative disease. Subsequent to its discovery over 45 years ago, epsteinbarr virus ebv has been associated with numerous human carcinomas. Frontiers the role of epsteinbarr virus in cervical. Key laboratory of carcinogenesis and invasion, chinese ministry of education, xiangya hospital, central south university, changsha 410078, china 2. Normal host populations can have vastly different susceptibility to ebvrelated tumors as demonstrated by geographical and immunological variations in the prevalence. Frontiers the role of epsteinbarr virus in cervical cancer.
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