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Current Opinion in Immunology Oct 2022Malignancies that arise as a result of viral infection account for roughly 15% of cancer cases worldwide. The innate immune system is the body's first line of defense... (Review)
Review
Malignancies that arise as a result of viral infection account for roughly 15% of cancer cases worldwide. The innate immune system is the body's first line of defense against oncogenic viral infection and is also involved in the response against viral-driven tumors. In this review, we discuss research advances made over the last five years elucidating how the innate immune system recognizes and responds to oncogenic viruses, how these viruses have evolved to escape this immune pressure, and ways that innate immunity can inform the development of novel therapeutics against oncogenic viral infection and their associated cancers.
Topics: Humans; Oncogenic Viruses; Immunity, Innate; Virus Diseases; Neoplasms; Biology
PubMed: 36240666
DOI: 10.1016/j.coi.2022.102253 -
Philosophical Transactions of the Royal... Oct 2017A viral etiology of cancer was first demonstrated in 1911 by Peyton Rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it... (Review)
Review
A viral etiology of cancer was first demonstrated in 1911 by Peyton Rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. Since the discovery over 50 years ago of the Epstein-Barr virus as the cause of Burkitt lymphoma, seven other human viruses or groups of viruses-hepatitis B virus, hepatitis C virus, human immunodeficiency virus type 1, some human papillomaviruses, human T-cell lymphotropic virus type 1, Kaposi sarcoma-associated herpesvirus and Merkel cell polyomavirus-have been linked to human cancer. Collectively, these eight viruses cause over 20 different types of cancer and contribute to 10-12% of all cancer, with a greater burden in low- and middle-income countries. For many viruses, immunosuppression greatly increases the risks of persistent infection, development of chronic sequelae and cancer. Although several viruses share similar routes of transmission (especially sexual activity, injection drug use and mother-to-child transmission), the predominant route of transmission varies across viruses, and for the same virus can vary by geographical location. In general, vulnerable populations at the greatest risk for viral infections and their associated diseases include people, especially children, living in low- to middle-income countries, men who have sex with men, people who use injection drugs and female sex workers.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: Humans; Oncogenic Viruses; Tumor Virus Infections
PubMed: 28893933
DOI: 10.1098/rstb.2016.0266 -
The FEBS Journal Dec 2022Epstein-Barr virus (EBV; human herpesvirus 4; HHV-4) and Kaposi sarcoma-associated herpesvirus (KSHV; human herpesvirus 8; HHV-8) are human gammaherpesviruses that have... (Review)
Review
Epstein-Barr virus (EBV; human herpesvirus 4; HHV-4) and Kaposi sarcoma-associated herpesvirus (KSHV; human herpesvirus 8; HHV-8) are human gammaherpesviruses that have oncogenic properties. EBV is a lymphocryptovirus, whereas HHV-8/KSHV is a rhadinovirus. As lymphotropic viruses, EBV and KSHV are associated with several lymphoproliferative diseases or plasmacytic/plasmablastic neoplasms. Interestingly, these viruses can also infect epithelial cells causing carcinomas and, in the case of KSHV, endothelial cells, causing sarcoma. EBV is associated with Burkitt lymphoma, classic Hodgkin lymphoma, nasopharyngeal carcinoma, plasmablastic lymphoma, lymphomatoid granulomatosis, leiomyosarcoma, and subsets of diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder, and gastric carcinoma. KSHV is implicated in Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease, and KSHV-positive diffuse large B-cell lymphoma. Pathogenesis by these two herpesviruses is intrinsically linked to viral proteins expressed during the lytic and latent lifecycles. This comprehensive review intends to provide an overview of the EBV and KSHV viral cycles, viral proteins that contribute to oncogenesis, and the current understanding of the pathogenesis and clinicopathology of their related neoplastic entities.
Topics: Humans; Epstein-Barr Virus Infections; Endothelial Cells; Herpesvirus 4, Human; Sarcoma, Kaposi; Herpesvirus 8, Human; Lymphoma, Large B-Cell, Diffuse; Viral Proteins
PubMed: 34536980
DOI: 10.1111/febs.16206 -
Annual Review of Virology Sep 2019I always loved biology and to do experiments. This passion and a great deal of good fortune and serendipity landed me in the field of retrovirology at the time when it... (Review)
Review
I always loved biology and to do experiments. This passion and a great deal of good fortune and serendipity landed me in the field of retrovirology at the time when it opened to experimental analysis. I became involved in viral replication, genetics, and viral oncogenes. In more recent years, I have applied what I learned in tumor virology to human cancer. The early years of my personal life were marked by displacements and migration: deportation into East Germany, escape to the West, and emigration to the United States. As a young man I faced heartbreaking personal tragedies but attained a peaceful and steady course in the second half of my life. I am fortunate to have found my home in Southern California and to continue in cancer research.
Topics: Germany; History, 20th Century; History, 21st Century; Humans; Oncogenes; Oncogenic Viruses; Retroviridae; United States; Viruses
PubMed: 31567064
DOI: 10.1146/annurev-virology-092818-015828 -
Philosophical Transactions of the Royal... Oct 2017Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for... (Review)
Review
Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for mucosal and cutaneous stratified squamous epithelial surfaces of the host. A subset of these viruses has been demonstrated to be the causative agent of several human cancers. Here, we review the biology, natural history, evolution and cancer association of the oncogenic HPVs.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: Carcinogenesis; Humans; Papillomaviridae; Papillomavirus Infections
PubMed: 28893940
DOI: 10.1098/rstb.2016.0273 -
Viruses Jul 2020Basic leucine zipper (bZIP) transcription factors (TFs) govern diverse cellular processes and cell fate decisions. The hallmark of the leucine zipper domain is the... (Review)
Review
Basic leucine zipper (bZIP) transcription factors (TFs) govern diverse cellular processes and cell fate decisions. The hallmark of the leucine zipper domain is the heptad repeat, with leucine residues at every seventh position in the domain. These leucine residues enable homo- and heterodimerization between ZIP domain α-helices, generating coiled-coil structures that stabilize interactions between adjacent DNA-binding domains and target DNA substrates. Several cancer-causing viruses encode viral bZIP TFs, including human T-cell leukemia virus (HTLV), hepatitis C virus (HCV) and the herpesviruses Marek's disease virus (MDV), Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). Here, we provide a comprehensive review of these viral bZIP TFs and their impact on viral replication, host cell responses and cell fate.
Topics: Animals; Basic-Leucine Zipper Transcription Factors; Deltaretrovirus; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Mardivirus; Oncogenic Viruses; Phylogeny; Tumor Virus Infections; Unfolded Protein Response
PubMed: 32674309
DOI: 10.3390/v12070757 -
Cancer Discovery Apr 2023The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous...
UNLABELLED
The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer. Unique breakpoints shared across structural variants facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that virus and virus-host concatemers are unstable and, upon insertion into and excision from chromosomes, facilitate capture, amplification, and recombination of host DNA and chromosomal rearrangements. Evidence of heterocateny was detected in extrachromosomal and intrachromosomal DNA. These findings indicate that heterocateny is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intratumoral heterogeneity and clonal evolution.
SIGNIFICANCE
Long-read sequencing of HPV-positive cancers revealed "heterocateny," a previously unreported form of genomic structural variation characterized by heterogeneous, interrelated, and repetitive genomic rearrangements within a tumor. Heterocateny is driven by unstable concatemerized HPV genomes, which facilitate capture, rearrangement, and amplification of host DNA, and promotes intratumoral heterogeneity and clonal evolution. See related commentary by McBride and White, p. 814. This article is highlighted in the In This Issue feature, p. 799.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Gene Rearrangement; Oropharyngeal Neoplasms; Clonal Evolution; Virus Integration; Papillomaviridae
PubMed: 36715691
DOI: 10.1158/2159-8290.CD-22-0900 -
Cells Jun 2023Kaposi's sarcoma-associated herpesvirus (KSHV) and the Epstein-Barr virus (EBV) are double-stranded DNA oncogenic gammaherpesviruses. These two viruses are associated... (Review)
Review
Kaposi's sarcoma-associated herpesvirus (KSHV) and the Epstein-Barr virus (EBV) are double-stranded DNA oncogenic gammaherpesviruses. These two viruses are associated with multiple human malignancies, including both B and T cell lymphomas, as well as epithelial- and endothelial-derived cancers. KSHV and EBV establish a life-long latent infection in the human host with intermittent periods of lytic replication. Infection with these viruses induce the expression of both viral and host RNA transcripts and activates several RNA sensors including RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), protein kinase R (PKR) and adenosine deaminases acting on RNA (ADAR1). Activation of these RNA sensors induces the innate immune response to antagonize the virus. To counteract this, KSHV and EBV utilize both viral and cellular proteins to block the innate immune pathways and facilitate their own infection. In this review, we summarize how gammaherpesviral infections activate RNA sensors and induce their downstream signaling cascade, as well as how these viruses evade the antiviral signaling pathways to successfully establish latent infection and undergo lytic reactivation.
Topics: Humans; RNA; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Herpesvirus 8, Human; Immunity, Innate; Latent Infection
PubMed: 37371120
DOI: 10.3390/cells12121650 -
Viral Immunology Jun 2023Epstein-Barr virus (EBV) is the first human oncogenic virus to be identified, which evades the body's immune surveillance through multiple mechanisms that allow... (Review)
Review
Epstein-Barr virus (EBV) is the first human oncogenic virus to be identified, which evades the body's immune surveillance through multiple mechanisms that allow long-term latent infection. Under certain pathological conditions, EBVs undergo a transition from the latent phase to the lytic phase and cause targeted dysregulation of the host immune system, leading to the development of EBV-related diseases. Therefore, an in-depth understanding of the mechanism of developing an immune response to EBV and the evasion of immune recognition by EBV is important for the understanding of the pathogenesis of EBV, which is of great significance for finding strategies to prevent EBV infection, and developing a therapy to treat EBV-associated diseases. In this review, we will discuss the molecular mechanisms of host immunological responses to EBV infection and the mechanisms of EBV-mediated immune evasion during chronic active infection.
Topics: Humans; Herpesvirus 4, Human; Immune Evasion; Epstein-Barr Virus Infections; Immune System
PubMed: 37285188
DOI: 10.1089/vim.2022.0200 -
Reviews in Medical Virology Jan 2020Oncogenic viruses are one of the most important causes of cancer worldwide. The pathogens contribute to the establishment of human malignancies by affecting various... (Review)
Review
Oncogenic viruses are one of the most important causes of cancer worldwide. The pathogens contribute to the establishment of human malignancies by affecting various cellular events. Epigenetic mechanisms, such as histone modification methylation/demethylation, are one of the most critical events manipulated by oncogenic viruses to drive tumorigenesis. Histone modifications are mediated by histone acetylation and deacetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Dysregulation of HDACs activity affects viral tumorigenesis in several ways, such as manipulating tumor suppressor and viral gene expression. The present review aims to describe the vital interactions between both cancer-caused/associated viruses and the HDAC machinery, particularly by focusing on those viruses involved in gastrointestinal tumors, as some of the most common viral-mediated cancers.
Topics: Animals; Cell Transformation, Viral; Disease Susceptibility; Gene Expression Regulation; Histone Acetyltransferases; Histone Deacetylases; Host-Pathogen Interactions; Humans; Neoplasms; Oncogenic Viruses; Tumor Virus Infections
PubMed: 31743548
DOI: 10.1002/rmv.2085