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Cell Sep 2022Epstein-Barr virus (EBV) is a ubiquitous, oncogenic virus that is associated with a number of different human malignancies as well as autoimmune disorders. The... (Review)
Review
Epstein-Barr virus (EBV) is a ubiquitous, oncogenic virus that is associated with a number of different human malignancies as well as autoimmune disorders. The expression of EBV viral proteins and non-coding RNAs contribute to EBV-mediated disease pathologies. The virus establishes life-long latency in the human host and is adept at evading host innate and adaptive immune responses. In this review, we discuss the life cycle of EBV, the various functions of EBV-encoded proteins and RNAs, the ability of the virus to activate and evade immune responses, as well as the neoplastic and autoimmune diseases that are associated with EBV infection in the human population.
Topics: Biology; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; RNA; Viral Proteins; Virus Latency
PubMed: 36113467
DOI: 10.1016/j.cell.2022.08.026 -
Seminars in Cancer Biology Nov 2022Despite decades of research, cancer continues to be a major global health concern. In recent years, the role played by microorganisms in the development and progression... (Review)
Review
Despite decades of research, cancer continues to be a major global health concern. In recent years, the role played by microorganisms in the development and progression of cancer has come under increased scrutiny. The aim of the present review is to highlight the main associations between members of the human oral microbiota and various cancers. The PubMed database was searched for available literature to outline the current state of understanding regarding the role of the oral microbiota and a variety of human cancers. Oral squamous cell carcinoma (OSCC) is associated with carriage of a number of oral bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.), certain viruses (e.g., human papilloma virus, human herpes virus 8, herpes simplex virus 1 and Epstein-Barr virus) and yeast (Candida albicans). Moreover, members of the oral microbiota are associated with cancers of the esophagus, stomach, pancreas, colon/rectum and lung. Furthermore, the present review outlines a number of the carcinogenic mechanisms underlying the presented microbial associations with cancer. Such information may one day help clinicians to diagnose neoplastic diseases at earlier stages and prescribe treatments that take into account the possible microbial nature of carcinogenesis.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Microbiota; Carcinogenesis; Head and Neck Neoplasms
PubMed: 34743032
DOI: 10.1016/j.semcancer.2021.11.002 -
Viruses Mar 2023Epstein-Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. It is associated with a large spectrum of... (Review)
Review
Epstein-Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. It is associated with a large spectrum of diseases, including benign diseases, a number of lymphoid malignancies, and epithelial cancers. EBV can also transform quiescent B lymphocytes into lymphoblastoid cell lines (LCLs) in vitro. Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. This review will highlight the history of EBV and current advances in EBV-associated diseases, focusing on how this virus provides a paradigm for exploiting the many insights identified through interplay between EBV and its host during oncogenesis, and other related non-malignant disorders.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; B-Lymphocytes; Cell Line; Carcinogenesis
PubMed: 36992423
DOI: 10.3390/v15030714 -
Pediatric Blood & Cancer Jul 2020Oncologists and cancer biologists are frequently confronted by the question of what causes cancer? This is particularly vexing for cancers affecting children and young... (Review)
Review
Oncologists and cancer biologists are frequently confronted by the question of what causes cancer? This is particularly vexing for cancers affecting children and young adults who have had limited exposure to environmental mutagens and the effects of aging. Here, I focus on a general framework of the causes of early-onset cancer development in children and young adults by relating inherited and constitutional cancer predisposition, oncogenic pathogens, and developmental mutations. This framework has implications not only for mechanistic investigation of young cancers, but should also clarify improved strategies for their treatment, screening, and potential prevention.
Topics: Adolescent; Carcinogens, Environmental; Child; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Medical Oncology; Mutagens; Mutation; Neoplasms; Neoplastic Syndromes, Hereditary; Oncogenic Viruses; Pediatrics; Young Adult
PubMed: 32391946
DOI: 10.1002/pbc.28335 -
Philosophical Transactions of the Royal... Oct 2017Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of... (Review)
Review
Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: Carcinogenesis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunocompetence; Immunocompromised Host; Lymphoma
PubMed: 28893938
DOI: 10.1098/rstb.2016.0271 -
Viruses Feb 2021Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in... (Review)
Review
Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.
Topics: Animals; DNA, Viral; Genome, Viral; Humans; Papillomaviridae; Papillomavirus Infections; Virus Replication
PubMed: 33672465
DOI: 10.3390/v13020321 -
Molecules (Basel, Switzerland) Mar 2019Epstein⁻Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is... (Review)
Review
Epstein⁻Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35⁻50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.
Topics: Animals; Antiviral Agents; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoma, B-Cell; Virus Replication
PubMed: 30871092
DOI: 10.3390/molecules24050997 -
Viruses Feb 2023Epstein-Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world's population. After primary infection-responsible for infectious mononucleosis in... (Review)
Review
Epstein-Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world's population. After primary infection-responsible for infectious mononucleosis in young adults-the virus persists lifelong in the infected host, especially in memory B cells. Viral persistence is usually without clinical consequences, although it can lead to EBV-associated cancers such as lymphoma or carcinoma. Recent reports also suggest a link between EBV infection and multiple sclerosis. In the absence of vaccines, research efforts have focused on virological markers applicable in clinical practice for the management of patients with EBV-associated diseases. Nasopharyngeal carcinoma is an EBV-associated malignancy for which serological and molecular markers are widely used in clinical practice. Measuring blood EBV DNA load is additionally, useful for preventing lymphoproliferative disorders in transplant patients, with this marker also being explored in various other EBV-associated lymphomas. New technologies based on next-generation sequencing offer the opportunity to explore other biomarkers such as the EBV DNA methylome, strain diversity, or viral miRNA. Here, we review the clinical utility of different virological markers in EBV-associated diseases. Indeed, evaluating existing or new markers in EBV-associated malignancies or immune-mediated inflammatory diseases triggered by EBV infection continues to be a challenge.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma; Lymphoproliferative Disorders; Nasopharyngeal Neoplasms
PubMed: 36992365
DOI: 10.3390/v15030656 -
Philosophical Transactions of the Royal... Oct 2017Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen... (Review)
Review
Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: Carcinoma; DNA Replication; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
PubMed: 28893937
DOI: 10.1098/rstb.2016.0270 -
Frontiers in Immunology 2022EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a... (Review)
Review
EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a significant contributor to the burden of autoimmune diseases. Thus, EBV represents a significant public health burden. Upon infection, EBV remains dormant in host cells for long periods of time. However, the presence or episodic reactivation of the virus increases the risk of transforming healthy cells to malignant cells that routinely escape host immune surveillance or of producing pathogenic autoantibodies. Cancers caused by EBV display distinct molecular behaviors compared to those of the same tissue type that are not caused by EBV, presenting opportunities for targeted treatments. Despite some encouraging results from exploration of vaccines, antiviral agents and immune- and cell-based treatments, the efficacy and safety of most therapeutics remain unclear. Here, we provide an up-to-date review focusing on underlying immune and environmental mechanisms, current therapeutics and vaccines, animal models and emerging technologies to study EBV-associated diseases that may help provide insights for the development of novel effective treatments.
Topics: Animals; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Immunologic Surveillance; Autoimmune Diseases; Neoplasms
PubMed: 36389670
DOI: 10.3389/fimmu.2022.1059133