The viruses in the human oncogénesis

Infectio ◽  
2018 ◽  
Vol 22 (4) ◽  
pp. 213
Author(s):  
Anggi Vélez-Bohórquez ◽  
Mabel Bohórquez-Lozano ◽  
Magdalena Echeverry-de-Polanco
Keyword(s):  
Tumor Suppressor ◽  
Hepatitis B ◽  
Tumor Suppressor Genes ◽  
Epstein Barr Virus ◽  
Oncogenic Potential ◽  
Barr Virus ◽  
Determining Factors ◽  
Oncogene Activation ◽  
Epstein Barr

Based on epidemiological associations and experimentation, relationships between viruses and cancer have been established. For more than 14 million new cases of cancer per year, it is estimated that 15% are related to viral agents. Epithelial, hematolymphoid and mesenchymal malignancies related to different viruses have been document such as Epstein Barr, Kaposi’s sarcoma, hepatitis B and C, human lymphotropic type 1, Merkel’s carcinoma and human papilloma. New virus with oncogenic potential such as cytomegalovirus, JC polyoma virus and BK have been described. The interaction of the viruses with the host induces oncogene activation, inhibition of tumor suppressor genes and activation of miRNAs, as determining factors in the development of cancer. The pathology is initiated with the infection that induces the deregulation of cell signaling. The Epstein Barr virus is the oncogenic prototype, with 1% of the human cancers related to it.

scholarly journals The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 127
Author(s):  
Adelaide Ohui Fierti ◽  
Michael Bright Yakass ◽  
Ernest Adjei Okertchiri ◽  
Samuel Mawuli Adadey ◽  
Osbourne Quaye
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressors ◽  
Tumor Suppressor Genes ◽  
Epstein Barr Virus ◽  
Epigenetic Silencing ◽  
Gene Products ◽  
Suppressor Genes ◽  
Barr Virus ◽  
Tumor Suppressor Proteins ◽  
Epstein Barr

Epstein-Barr virus (EBV) is ubiquitous and carried by approximately 90% of the world’s adult population. Several mechanisms and pathways have been proposed as to how EBV facilitates the pathogenesis and progression of malignancies, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and gastric cancers, the majority of which have been linked to viral proteins that are expressed upon infection including latent membrane proteins (LMPs) and Epstein-Barr virus nuclear antigens (EBNAs). EBV expresses microRNAs that facilitate the progression of some cancers. Mostly, EBV induces epigenetic silencing of tumor suppressor genes, degradation of tumor suppressor mRNA transcripts, post-translational modification, and inactivation of tumor suppressor proteins. This review summarizes the mechanisms by which EBV modulates different tumor suppressors at the molecular and cellular levels in associated cancers. Briefly, EBV gene products upregulate DNA methylases to induce epigenetic silencing of tumor suppressor genes via hypermethylation. MicroRNAs expressed by EBV are also involved in the direct targeting of tumor suppressor genes for degradation, and other EBV gene products directly bind to tumor suppressor proteins to inactivate them. All these processes result in downregulation and impaired function of tumor suppressors, ultimately promoting malignances.

scholarly journals Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
Qianli Wang ◽  
Amy Lingel ◽  
Vicki Geiser ◽  
Zachary Kwapnoski ◽  
Luwen Zhang
Keyword(s):  
Dna Damage ◽  
Tumor Suppressor ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Tumor Suppressor P53 ◽  
Viral Oncogene ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo. The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and DNA damage-mediated cellular stresses. This seems to be the first report that p53 activates a viral oncogene; therefore, the discovery would be interesting to a broad readership from the fields of oncology to virology.

Application of Epstein-Barr Virus Serology to the Diagnosis and Staging of North American Patients with Nasopharyngeal Carcinoma

1983 ◽  
Vol 91 (3) ◽  
pp. 255-262 ◽  
Author(s):  
H. Bryan Neel ◽  
Gary R. Pearson ◽  
Louis H. Weiland ◽  
William F. Taylor ◽  
Helmut H. Goepfert ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
North American ◽  
Epstein Barr Virus ◽  
Geometric Mean ◽  
World Health ◽  
Barr Virus ◽  
Staging Systems ◽  
Antibody Titers ◽  
Epstein Barr

From 1978 to 1981, 151 patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective, collaborative study of North American patients, most of them white. Thirty-seven had World Health Organization (WHO) type 1 tumors, and 114 had WHO types 2 and 3 tumors. The anti-Epstein-Barr virus (EBV) profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in 85% of the patients with WHO types 2 and 3 tumors but in only 16% of the patients with WHO type 1 tumors. Geometric mean titers tended to be higher in higher stages of the disease in several staging systems. Low antibody-dependent cellular cytotoxicity at diagnosis appears to reflect a poorer prognosis, and the determination of antibody titers by this assay may prove to be useful for identifying persons in whom recurrent disease is likely to develop after conventional therapy. Anti-EBV titers can aid in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.

Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 949-954
Author(s):  
Alan L. Bisno
Keyword(s):  
Herpes Simplex ◽  
Influenza A ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
Acute Pharyngitis ◽  
Herpesvirus Type ◽  
Barr Virus ◽  
Epstein Barr

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.

scholarly journals Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

2019 ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

scholarly journals Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1579-1585 ◽  
Author(s):  
V Schuster ◽  
G Ott ◽  
S Seidenspinner ◽  
HW Kreth
Keyword(s):  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Sequence Pattern ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils of EBV- seropositive children and from peripheral blood mononuclear cells of 12 children with uncomplicated infectious mononucleosis (IM) and of a boy with severe chronic active EBV infection were genotyped in the EBV nuclear antigen-2 (EBNA-2) gene. A total of 40 of 41 isolates harbored EBV type 1; in 1 specimen (tonsil), only EBV type 2 was found. Further molecular characterization of EBV type-1 wild-type isolates in the EBNA- 2 gene and in the 40-kb distant EBV-encoded small RNAs (EBER) region showed that different groups of stable EBV type-1 variant strains exist in vivo both in benign and malignant lymphatic tissue. Group 1 is composed of EBV type-1 isolates (B-NHL, n = 3; T-NHL, n = 1; HD, n = 1; IM, n = 4) that showed a B95–8-like DNA sequence pattern in both viral genes. Group 2 isolates (HD, n = 1; AILD, n = B-NHL, n = 1; tonsils of EBV-seropositive children, n = 9; IM, n = 20 showed a nucleotide change at position 49095 in the EBNA-2 gene, leading to an amino acid substitution (Pro-->Ser), and EBV type-2 sequences in the EBER region. EBV type-1 isolates that fall into group 3 (AILD, n = 3; HD, n = 1; B- NHL, n = 4; gastric carcinoma, n = 2; IM, n = 6; severe chronic active EBV infection, n = 1) were characterized by typical nucleotide changes and a 3-bp insertion (CTC; extra Leu residue) in the EBNA-2 gene and an EBV type-2-specific sequence pattern in the EBER region. These EBV type- 1 variant strains may represent the most prevalent circulating EBV type- 1 strains in the exposed population and seem not to be restricted to a certain EBV-associated disease or tumor type. However, analysis of more EBV isolates from benign and malignant lesions must show whether more EBV type-1 substrains exist in vivo.

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