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International Journal of Molecular... Aug 2023Epstein‑Barr virus (EBV) is an oncovirus associated with various neoplasms, including breast cancer (BC). EBV‑associated oncogenesis requires the action of several... (Review)
Review
Epstein‑Barr virus (EBV) is an oncovirus associated with various neoplasms, including breast cancer (BC). EBV‑associated oncogenesis requires the action of several viral molecules, such as EBV nuclear antigen 3C, latent membrane protein 1, microRNAs and long non‑coding RNAs, which are able of manipulating the cellular machinery, inducing an evasion of the immune system, blocking apoptosis processes, promoting cell survival and metastasis. The risk of developing cancer is associated with epigenetic alterations and alterations in various signaling pathways. The activation of all these molecules can modify the expression of EBV proteins with oncogenic activity, influencing the oncogenic process. It is clear that BC, being multifactorial, presents a greater complexity; in numerous cases, the infection associated with EBV may be crucial for this neoplasia, if particular conditions for both the virus and host are present. In the present review, all these variables are analyzed in an aim to improve the understanding of the participation of EBV in BC.
Topics: Humans; Female; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Breast Neoplasms; Tumor Microenvironment; Cell Transformation, Neoplastic; Carcinogenesis
PubMed: 37417334
DOI: 10.3892/ijmm.2023.5275 -
MethodsX 2020It is currently difficult to determine the effect of oncogenic viruses on the global function and regulation of pathways within mammalian cells. A thorough understanding...
It is currently difficult to determine the effect of oncogenic viruses on the global function and regulation of pathways within mammalian cells. A thorough understanding of the molecular pathways and individual genes altered by oncogenic viruses is needed for the identification of targets that can be utilised for early diagnosis, prevention, and treatment methods. We detail a logical step-by-step guide to uncover viral-protein-miRNA interactions using publically available datasets and the network building program, Cytoscape. This method may be applied to identify specific pathways that are altered in viral infection, and contribute to the oncogenic transformation of cells. To demonstrate this, we constructed a gene regulatory interactome encompassing Human Papillomavirus Type 16 (HPV16) and its control of specific miRNAs. This approach can be broadly applied to understand and map the regulatory functions of other oncogenic viruses, and determine their role in altering the cellular environment in cancer. Cytoscape (Shannon et al. (2003), Smoot et al. (2010)) is freely available at https://cytoscape.org/. ••
PubMed: 31993337
DOI: 10.1016/j.mex.2019.10.011 -
Pathogens (Basel, Switzerland) Jul 2022Viral infections are major contributors to the global cancer burden. Recent advances have revealed that known oncogenic viruses promote carcinogenesis through shared... (Review)
Review
Viral infections are major contributors to the global cancer burden. Recent advances have revealed that known oncogenic viruses promote carcinogenesis through shared host cell targets and pathways. The aim of this review is to point out the connection between several oncogenic viruses from the , and families and renal carcinogenesis, highlighting their involvement in the carcinogenic mechanism. We performed a systematic search of the PubMed and EMBASE databases, which was carried out for all the published studies on RCC in the last 10 years, using the following search algorithm: renal cell carcinoma (RCC) and urothelial carcinoma, and oncogenic viruses (BKPyV, EBV, HCV, HPV and Kaposi Sarcoma Virus), RCC and biomarkers, immunohistochemistry (IHC). Our analysis included studies that were published in English from the 1st of January 2012 to the 1st of May 2022 and that described and analyzed the assays used for the detection of oncogenic viruses in RCC and urothelial carcinoma. The virus most frequently associated with RCC was BKPyV. This review of the literature will help to understand the pathogenic mechanism of the main type of renal malignancy and whether the viral etiology can be confirmed, at a minimum, as a co-factor. In consequence, these data can contribute to the development of new therapeutic strategies. A virus-induced tumor could be efficiently prevented by vaccination or treatment with oncolytic viral therapy and/or by targeted therapy.
PubMed: 35890003
DOI: 10.3390/pathogens11070757 -
Viruses Dec 2022Epstein-Barr virus (EBV) is an oncogenic human herpesvirus infecting approximately 90% of the world's population. The oral cavity serves a central role in the life... (Review)
Review
Epstein-Barr virus (EBV) is an oncogenic human herpesvirus infecting approximately 90% of the world's population. The oral cavity serves a central role in the life cycle, transmission, and pathogenesis of EBV. Transmitted to a new host via saliva, EBV circulates between cellular compartments within oral lymphoid tissues. Epithelial cells primarily support productive viral replication, while B lymphocytes support viral latency and reactivation. EBV infections are typically asymptomatic and benign; however, the latent virus is associated with multiple lymphomas and carcinomas arising in the oral cavity. EBV association with cancer is complex as histologically similar cancers often test negative for the virus. However, the presence of EBV is associated with distinct features in certain cancers. The intrinsic ability of EBV to immortalize B-lymphocytes, via manipulation of survival and growth signaling, further implicates the virus as an oncogenic cofactor. A distinct mutational profile and burden have been observed in EBV-positive compared to EBV-negative tumors, suggesting that viral infection can drive alternative pathways that converge on oncogenesis. Taken together, EBV is also an important prognostic biomarker that can direct alternative therapeutic approaches. Here, we discuss the prevalence of EBV in oral malignancies and the EBV-dependent mechanisms associated with tumorigenesis.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Lymphoma; Carcinoma; B-Lymphocytes
PubMed: 36560704
DOI: 10.3390/v14122700 -
Viruses Mar 2024Approximately 12% of human cancers worldwide are associated with infectious agents, which are classified by the International Agency for Research on Cancer (IARC) as... (Review)
Review
Approximately 12% of human cancers worldwide are associated with infectious agents, which are classified by the International Agency for Research on Cancer (IARC) as Group 1 within the agents that are carcinogenic to humans. Most of these agents are viruses. Group 1 oncogenic viruses include hepatitis C virus, hepatitis B virus (HBV), human T-cell lymphotropic virus type 1, Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human immunodeficiency virus-1 and high-risk human papillomaviruses (HPVs). In addition, some human polyomaviruses are suspected of inducing cancer prevalently in hosts with impaired immune responses. Merkel cell polyomavirus has been associated with Merkel cell carcinoma and included by the IARC in Group 2A (i.e., probably carcinogenic to humans). Linking viruses to human cancers has allowed for the development of diagnostic, prophylactic and therapeutic measures. Vaccination significantly reduced tumours induced by two oncogenic viruses as follows: HBV and HPV. Herein, we focus on mucosal alpha HPVs, which are responsible for the highest number of cancer cases due to tumour viruses and against which effective prevention strategies have been developed to reduce the global burden of HPV-related cancers.
Topics: Humans; Oncogenic Viruses; Human Papillomavirus Viruses; Papillomavirus Infections; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasms; Viruses; Carcinogenesis; Hepatitis B virus
PubMed: 38543781
DOI: 10.3390/v16030416 -
Klinicka Onkologie : Casopis Ceske a... 2019Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to... (Review)
Review
BACKGROUND
Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor. Viral proteins functionally inactivate p53 and deregulate the expression of proteins active during apoptosis, cell proliferation and DNA damage response. Hepatitis virus B HbX protein and hepatitis virus C proteins NS2 and NS5A interact with p53 and prevent its localisation to the nucleus and thus reduce its transcriptional activity. Another mechanism lies in elevated p53 degradation caused by the BZLF1 protein of the Epstein-Barr virus, the LANA protein of the Kaposi sarcoma virus and human papilloma virus E6. The Merkel cell polyomavirus large T antigen does not interact directly with p53, however it acts through downregulation of p53 mediated transcription. The tax protein of human T cell lymphotropic virus type 1 modifies p53 posttranslationally and thus blocks its interaction with other factors of transcription machinery. Due to its tumour suppressor function and role in the maintenance of the genome integrity, the p53 protein is one of the best studied proteins. Following this, evolutionary homologues with important developmental functions p63 and p73 are intensively studied as well. Their roles in oncogenesis have not been clarified yet.
PURPOSE
This review describes some of their known interactions with oncogenic viral proteins.
Topics: Carcinogenesis; Host-Pathogen Interactions; Humans; Multigene Family; Neoplasms; Oncogenic Viruses; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Viral Proteins
PubMed: 31627709
DOI: 10.14735/amko20193S -
Biochimica Et Biophysica Acta. Reviews... Aug 2021Accumulated evidence from genetically modified cell and animal models indicates that centrosome amplification (CA) can initiate tumorigenesis with metastatic potential... (Review)
Review
Accumulated evidence from genetically modified cell and animal models indicates that centrosome amplification (CA) can initiate tumorigenesis with metastatic potential and enhance cell invasion. Multiple human diseases are associated with CA and carcinogenesis as well as metastasis, including infection with oncogenic viruses, type 2 diabetes, toxicosis by environmental pollution and inflammatory disease. In this review, we summarize (1) the evidence for the roles of CA in tumorigenesis and tumor cell invasion; (2) the association between diseases and carcinogenesis as well as metastasis; (3) the current knowledge of CA in the diseases; and (4) the signaling pathways of CA. We then give our own thinking and discuss perspectives relevant to CA in carcinogenesis and cancer metastasis in human diseases. In conclusion, investigations in this area might not only identify CA as a biological link between these diseases and the development of cancer but also prove the causal role of CA in cancer and progression under pathophysiological conditions, potentially taking cancer research into a new era.
Topics: Animals; Cell Movement; Cell Transformation, Neoplastic; Centrosome; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Signal Transduction
PubMed: 33992724
DOI: 10.1016/j.bbcan.2021.188566 -
International Journal of Molecular... Aug 2023The two oncogenic human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause significant disease burden, particularly in... (Review)
Review
The two oncogenic human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause significant disease burden, particularly in immunosuppressed individuals. Both viruses display latent and lytic phases of their life cycle with different outcomes for their associated pathologies. The high prevalence of infectious diseases in Sub-Saharan Africa (SSA), particularly HIV/AIDS, tuberculosis, malaria, and more recently, COVID-19, as well as their associated inflammatory responses, could potentially impact either virus' infectious course. However, acute or lytically active EBV and/or KSHV infections often present with symptoms mimicking these predominant diseases leading to misdiagnosis or underdiagnosis of oncogenic herpesvirus-associated pathologies. EBV and/or KSHV infections are generally acquired early in life and remain latent until lytic reactivation is triggered by various stimuli. This review summarizes known associations between infectious agents prevalent in SSA and underlying EBV and/or KSHV infection. While presenting an overview of both viruses' biphasic life cycles, this review aims to highlight the importance of co-infections in the correct identification of risk factors for and diagnoses of EBV- and/or KSHV-associated pathologies, particularly in SSA, where both oncogenic herpesviruses as well as other infectious agents are highly pervasive and can lead to substantial morbidity and mortality.
Topics: Humans; Herpesvirus 4, Human; Coinfection; Epstein-Barr Virus Infections; COVID-19; Gammaherpesvirinae; Herpesvirus 8, Human; Acquired Immunodeficiency Syndrome
PubMed: 37685871
DOI: 10.3390/ijms241713066 -
Recent Results in Cancer Research.... 2021Seven viruses including the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency...
Seven viruses including the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by the International Agency for Research on Cancer (IARC). The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; and HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection, high viral load, and viral genotype are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral risk predictors have been developed for the prediction of long-term risk of hepatocellular carcinoma, nasopharyngeal carcinoma and cervical cancer. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization, antiviral therapy and screening have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future research on gene-gene and gene-environment interactions of oncogenic viruses and the human host using large-scale longitudinal studies with serial measurements of biosignatures are in urgent need.
Topics: Carcinoma, Hepatocellular; Herpesvirus 4, Human; Humans; Liver Neoplasms; Neoplasms; Oncogenic Viruses; Virus Diseases
PubMed: 33200360
DOI: 10.1007/978-3-030-57362-1_2 -
Proceedings of the National Academy of... Feb 2023Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions; oncogenic viruses like Kaposi's sarcoma herpesvirus (KSHV) employ ncRNAs to establish a...
Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions; oncogenic viruses like Kaposi's sarcoma herpesvirus (KSHV) employ ncRNAs to establish a latent reservoir and persist for the life of the host. We previously reported that KSHV infection alters a novel class of RNA, circular RNAs (circRNAs). CircRNAs are alternative splicing isoforms and regulate gene expression, but their importance in infection is largely unknown. Here, we showed that a human circRNA, hsa_circ_0001400, is induced by various pathogenic viruses, namely KSHV, Epstein-Barr virus, and human cytomegalovirus. The induction of circRNAs including circ_0001400 by KSHV is co-transcriptionally regulated, likely at splicing. Consistently, screening for circ_0001400-interacting proteins identified a splicing factor, PNISR. Functional studies using infected primary endothelial cells revealed that circ_0001400 inhibits KSHV lytic transcription and virus production. Simultaneously, the circRNA promoted cell cycle, inhibited apoptosis, and induced immune genes. RNA-pull down assays identified transcripts interacting with circ_0001400, including , which is a component of the pro-growth mTOR complexes. We thus identified a circRNA that is pro-growth and anti-lytic replication. These results support a model in which KSHV induces circ_0001400 expression to maintain latency. Since circ_0001400 is induced by multiple viruses, this novel viral strategy may be widely employed by other viruses.
Topics: Humans; Herpesvirus 8, Human; RNA, Circular; Sarcoma, Kaposi; Endothelial Cells; Epstein-Barr Virus Infections; Virus Latency; Herpesvirus 4, Human; RNA, Viral; Latent Infection; RNA, Untranslated; RNA Viruses; Virus Replication; Gene Expression Regulation, Viral
PubMed: 36724259
DOI: 10.1073/pnas.2212864120