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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 -
Frontiers in Public Health 2020Diagnosed in more than 90% of cervical cancers, the fourth deadliest cancer in women, human papillomavirus (HPV) is currently the most common pathogen responsible for... (Review)
Review
Diagnosed in more than 90% of cervical cancers, the fourth deadliest cancer in women, human papillomavirus (HPV) is currently the most common pathogen responsible for female cancers. Moreover, HPV infection is associated with many other diseases, including cutaneous and anogenital warts, and genital and upper aerodigestive tract cancers. The incidence and prevalence of these pathologies vary considerably depending on factors including HPV genotype, regional conditions, the study population, and the anatomical site sampled. Recently, features of the cervicovaginal microbiota are found to be associated with the incidence of HPV-related diseases, presenting a novel approach to identify high-risk women through both blood and cervical samples. Overall, the HPV repartition data show that HPV infection and related diseases are more prevalent in developing countries. Moreover, the available (2-, 4-, and 9-valent) vaccines based on virus-like particles, despite their proven effectiveness and safety, present some limitations in terms of system development cost, transport cold chain, and oncogenic HPV variants. In addition, vaccination programs face some challenges, leading to a considerable burden of HPV infection and related diseases. Therefore, even though the new (9-valent) vaccine seems promising, next-generation vaccines as well as awareness programs associated with HPV vaccination and budget reinforcements for immunization are needed.
Topics: Alphapapillomavirus; Female; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms
PubMed: 33553082
DOI: 10.3389/fpubh.2020.552028 -
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 -
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 -
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 -
Cell Death and Differentiation Aug 2022Epstein-Barr virus (EBV) was the first oncogenic virus identified in humans. It is primarily associated with multiple lymphoid and epithelial cancers, including...
Epstein-Barr virus (EBV) was the first oncogenic virus identified in humans. It is primarily associated with multiple lymphoid and epithelial cancers, including nasopharyngeal carcinoma (NPC). However, its association with ferroptosis and its role in cancer therapy resistance have not been fully elucidated. Here, we show that EBV infection reduces the sensitivity of NPC cells to ferroptosis by activating the p62-Keap1-NRF2 signaling pathway in conjunction with upregulation of SLC7A11 and GPX4 expression. Knockdown of endogenous GPX4 or blockade of GPX4 using a specific inhibitor enhanced the chemosensitivity of EBV-infected NPC cells. Functional studies revealed that GPX4 knockdown suppresses the proliferation and colony formation of NPC cells. Mechanistically, GPX4 interacts with the TAK1-TAB1/TAB3 complex, regulates TAK1 kinase activity, and further activates downstream MAPK-JNK and NFκB pathways. High GPX4 expression is correlated with poor clinical outcomes in patients with NPC and other cancer types. Taken together, our findings suggest that EBV infection has important effects on redox homeostasis, revealing a previously unappreciated role for GPX4 in tumor progression. This novel mechanism provides a potential new target for the treatment of EBV-related tumors.
Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase
PubMed: 35105963
DOI: 10.1038/s41418-022-00939-8 -
Frontiers in Cellular and Infection... 2022Men should not be overlooked in research on human papillomavirus (HPV) and its associated genital diseases. This is because men infected with HPV are not only at higher... (Review)
Review
Men should not be overlooked in research on human papillomavirus (HPV) and its associated genital diseases. This is because men infected with HPV are not only at higher risk of genital cancers, but also increase their partners' risk of HPV infection and reinfection through sexual contact. Herein, we summarized the state of knowledge regarding the prevention and treatment of HPV infection in men as well as the possible effects of the prevention and treatment of HPV in men on their female partners. Condom use, smoking cessation, male circumcision, and HPV vaccination for men each play an important role in preventing HPV infection within heterosexual couples. Additionally, men could choose to test for certain types of HPV, such as the oncogenic HPV16 or HPV18 strains, as part of a routine screening program when their partner is positive for HPV. Although there is no recognized treatment for HPV infection as of yet, immunotherapy drugs, such as toll-like receptor agonists, therapeutic HPV vaccines, and immune checkpoint inhibitors, have shown promising results in clinical trials and in actual clinical practice. HPV infection in men also increases the risk of cervical cancer in their female partners. Because of the high partner concordance for HPV demonstrated in prior research, the prevention and treatment of HPV in men should be explored more comprehensively in future research.
Topics: Female; Humans; Male; Human Papillomavirus Viruses; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Human papillomavirus 16
PubMed: 36506029
DOI: 10.3389/fcimb.2022.1077651