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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 -
Frontiers in Immunology 2014Human oncogenic viruses include Epstein-Barr virus, hepatitis B virus, hepatitis C virus, human papilloma virus, human T-cell lymphotropic virus, Kaposi's associated... (Review)
Review
Human oncogenic viruses include Epstein-Barr virus, hepatitis B virus, hepatitis C virus, human papilloma virus, human T-cell lymphotropic virus, Kaposi's associated sarcoma virus, and Merkel cell polyomavirus. It would be expected that during virus-host interaction, the immune system would recognize these pathogens and eliminate them. However, through evolution, these viruses have developed a number of strategies to avoid such an outcome and successfully establish chronic infections. The persistent nature of the infection caused by these viruses is associated with their oncogenic potential. In this article, we will review the latest information on the interaction between oncogenic viruses and the innate immune system of the host. In particular, we will summarize the available knowledge on the recognition by host pattern-recognition receptors of pathogen-associated molecular patterns present in the incoming viral particle or generated during the virus' life cycle. We will also review the data on the recognition of cell-derived danger associated molecular patterns generated during the virus infection that may impact the outcome of the host-pathogen interaction and the development cancer.
PubMed: 25101093
DOI: 10.3389/fimmu.2014.00353 -
Advances in Experimental Medicine and... 2016Over 12 % of all human cancers are caused by oncoviruses, primarily including Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C... (Review)
Review
Over 12 % of all human cancers are caused by oncoviruses, primarily including Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), and Kaposi's sarcoma herpesvirus (KSHV). In addition to viral oncoproteins, a variety of noncoding RNAs (ncRNAs) produced by oncoviruses have been recognized as important cofactors that contribute to the oncogenic events. In this chapter, we will focus on the recent understanding of the long and short noncoding RNAs, as well as microRNAs of the viruses, and discuss their roles in the biology of multistep oncogenesis mediated by established human oncoviruses.
Topics: Gene Expression Regulation, Neoplastic; Hepacivirus; Hepatitis B virus; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; MicroRNAs; Neoplasms; Papillomaviridae; RNA, Long Noncoding; RNA, Small Untranslated
PubMed: 27376743
DOI: 10.1007/978-981-10-1498-7_14 -
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 -
Viruses Sep 2017Approximately 15-20% of human cancers are caused by viruses, including human papillomaviruses (HPVs). Viruses are obligatory intracellular parasites and encode proteins... (Review)
Review
Approximately 15-20% of human cancers are caused by viruses, including human papillomaviruses (HPVs). Viruses are obligatory intracellular parasites and encode proteins that reprogram the regulatory networks governing host cellular signaling pathways that control recognition by the immune system, proliferation, differentiation, genomic integrity, and cell death. Given that key proteins in these regulatory networks are also subject to mutation in non-virally associated diseases and cancers, the study of oncogenic viruses has also been instrumental to the discovery and analysis of many fundamental cellular processes, including messenger RNA (mRNA) splicing, transcriptional enhancers, oncogenes and tumor suppressors, signal transduction, immune regulation, and cell cycle control. More recently, tumor viruses, in particular HPV, have proven themselves invaluable in the study of the cancer epigenome. Epigenetic silencing or de-silencing of genes can have cellular consequences that are akin to genetic mutations, i.e., the loss and gain of expression of genes that are not usually expressed in a certain cell type and/or genes that have tumor suppressive or oncogenic activities, respectively. Unlike genetic mutations, the reversible nature of epigenetic modifications affords an opportunity of epigenetic therapy for cancer. This review summarizes the current knowledge on epigenetic regulation in HPV-infected cells with a focus on those elements with relevance to carcinogenesis.
Topics: Acetylation; Carcinogenesis; Cell Cycle Checkpoints; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic; Cell Transformation, Viral; DNA Methylation; Epigenesis, Genetic; Epigenomics; Genome, Viral; Histones; Humans; Oncogene Proteins, Viral; Oncogenic Viruses; Papillomaviridae; Papillomavirus Infections; RNA Splicing; Signal Transduction; Tumor Suppressor Proteins
PubMed: 28862667
DOI: 10.3390/v9090248 -
Current Pharmaceutical Design 2017About 15-20% of human cancers worldwide have viral etiology. Seven human DNA and RNA viruses are accepted to be oncogenic viruses or oncoviruses and contribute to the... (Review)
Review
About 15-20% of human cancers worldwide have viral etiology. Seven human DNA and RNA viruses are accepted to be oncogenic viruses or oncoviruses and contribute to the development of various cancer types. Human oncoviruses have developed multiple molecular mechanisms to interfere with specific cellular pathways to promote viral replication and viral life cycle maintenance in the host. Despite the diversity of oncogenic viruses, they use similar strategies for cancer development. Viral oncoproteins and viral non-coding RNAs are the key factors that can affect multiple cellular processes on both genetic and epigenetic levels. Epigenetics research allows better understanding of the complex interplay between oncoviruses and the host cells. This review highlights the importance of epigenetic reprogramming for virus-induced carcinogenesis. Recent progress in the development of pharmacological tools for targeting epigenetic mechanisms opens new perspectives for modulation of virus/host interaction and intervention of virus-induced cancer. Several clinical trials have been carried out or are on-going involving epigenetic drugs not only as single therapeutic but also in combination with other targeted agents against various virus-induced cancers.
Topics: Animals; Antineoplastic Agents; Carcinogenesis; Epigenesis, Genetic; Humans; Molecular Targeted Therapy; Neoplasms; Oncogenic Viruses; RNA, Viral; Virus Replication
PubMed: 28828983
DOI: 10.2174/1381612823666170822100627 -
Reviews in Medical Virology Sep 2018The Notch pathway is a conserved signaling pathway and a form of direct cell-cell communication related to many biological processes during development and adulthood.... (Review)
Review
The Notch pathway is a conserved signaling pathway and a form of direct cell-cell communication related to many biological processes during development and adulthood. Deregulation of the Notch pathway is involved in many diseases, including cancer. Almost 20% of all cancer cases have an infectious etiology, with viruses responsible for at least 1.5 million new cancer cases per year. Seven groups of viruses have been classified as oncogenic: hepatitis B and C viruses (HBV and HCV respectively), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), human T lymphotropic virus (HTLV-1), human papillomavirus (HPV), and Merkel cell polyomavirus (MCPyV). These viruses share the ability to manipulate a variety of cell pathways that are critical in proliferation and differentiation, leading to malignant transformation. Viral proteins interact directly or indirectly with different members of the Notch pathway, altering their normal function. This review focuses exclusively on the direct interactions of viral oncoproteins with Notch elements, providing a deeper understanding of the dual behavior of the Notch pathway as activator or suppressor of neoplasia in virus-related cancers.
Topics: Animals; Biomarkers; Cell Transformation, Neoplastic; Cell Transformation, Viral; Disease Susceptibility; Humans; Neoplasms; Oncogenic Viruses; Protein Binding; Receptors, Notch; Signal Transduction
PubMed: 29956408
DOI: 10.1002/rmv.1988 -
Frontiers in Oncology 2024
PubMed: 38660129
DOI: 10.3389/fonc.2024.1402877 -
Viruses Dec 2022The two human tumor viruses, Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), have been mostly studied in isolation. Recent studies suggest... (Review)
Review
The two human tumor viruses, Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), have been mostly studied in isolation. Recent studies suggest that co-infection with both viruses as observed in one of their associated malignancies, namely primary effusion lymphoma (PEL), might also be required for KSHV persistence. In this review, we discuss how EBV and KSHV might support each other for persistence and lymphomagenesis. Moreover, we summarize what is known about their innate and adaptive immune control which both seem to be required to ensure asymptomatic persistent co-infection with these two human tumor viruses. A better understanding of this immune control might allow us to prepare for vaccination against EBV and KSHV in the future.
Topics: Humans; Herpesvirus 4, Human; Herpesvirus 8, Human; Epstein-Barr Virus Infections; Coinfection; Neoplasms; Oncogenic Viruses; Sarcoma, Kaposi
PubMed: 36560713
DOI: 10.3390/v14122709 -
Archives of Pathology & Laboratory... May 2021Epstein-Barr virus is a ubiquitous oncogenic virus. During the past 5 decades, the virus has been linked to several disease entities, both neoplastic and nonneoplastic.... (Review)
Review
CONTEXT.—
Epstein-Barr virus is a ubiquitous oncogenic virus. During the past 5 decades, the virus has been linked to several disease entities, both neoplastic and nonneoplastic. Several Epstein-Barr virus-associated conditions affect the digestive organs, ranging from mild transient inflammatory conditions to more debilitating and even fatal diseases.
OBJECTIVE.—
To discuss the clinicopathologic aspects of some newly or recently recognized Epstein-Barr virus-related conditions encountered in the digestive system and their therapeutic implications.
DATA SOURCES.—
Published peer-reviewed literature was reviewed.
CONCLUSIONS.—
This article highlights the importance of recognizing the discussed lesions because they influence the direct clinical management or serve as a potential predictive marker for therapy.
Topics: Digestive System Neoplasms; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans
PubMed: 32320275
DOI: 10.5858/arpa.2019-0703-RA