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Veterinary and Comparative Oncology Mar 2021Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic... (Review)
Review
Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation of the interactions between high-risk papillomavirus oncoproteins and programmed cell-death pathways. It further exemplifies the role of these interactions in the malignant cell transformation process. In parallel with this, the use and importance of the bovine model system to enlighten the papillomavirus-associated cancers is discussed with an in-depth examination. Furthermore, it focuses on the epidemiological situation of BPV infections in Turkey in the cattle herds.
Topics: Animals; Carcinogenesis; Cell Differentiation; Gene Expression Regulation, Viral; Genome, Viral; Humans; Papillomaviridae; Papillomavirus Infections
PubMed: 33084187
DOI: 10.1111/vco.12659 -
Microbial Pathogenesis Oct 2023Cancer is a serious public health problem globally. Many human cancers are induced by viruses. Understanding of the mechanisms by which oncogenic (tumorigenic) viruses... (Review)
Review
Cancer is a serious public health problem globally. Many human cancers are induced by viruses. Understanding of the mechanisms by which oncogenic (tumorigenic) viruses induce cancer is essential in the prevention and control of cancer. This review covers comprehensive characteristics and molecular mechanisms of the main virus-attributed cancers caused by human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human herpesvirus type 8, human T-cell lymphotropic virus, human polyomaviruses, Merkel cell polyomavirus, and HIV. Oncogenic viruses employ biological processes to replicate and avoid detection by host cell immune systems. Tumorigenic infectious agents activate oncogenes in a variety of ways, allowing the pathogen to block host tumour suppressor proteins, inhibit apoptosis, enhance cell proliferation, and promote invasion of host cells. Furthermore, this review assesses many pathways of viruses linked to cancer, including host cellular communication perturbation, DNA damage mechanisms, immunity, and microRNA targets that promote the beginning and progression of cancer. The current cancer prevention is primarily focused on non-communicable diseases, but infection-attributable cancer also needs attention to significantly reduce the rising cancer burden and related deaths.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasms; Oncogenic Viruses; Hepacivirus
PubMed: 37557930
DOI: 10.1016/j.micpath.2023.106292 -
Annual Review of Virology Sep 2020Among all of the known biological carcinogens, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are two of the classical oncogenic... (Review)
Review
Among all of the known biological carcinogens, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are two of the classical oncogenic herpesviruses known to induce the oncogenic phenotype. Many studies have revealed important functions related to epigenetic alterations of the EBV and KSHV genomes that mediate oncogenesis, but the detailed mechanisms are not fully understood. It is also challenging to fully describe the critical cellular events that drive oncogenesis as well as a comprehensive map of the molecular contributors. This review introduces the roles of epigenetic modifications of these viral genomes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA expression, and elucidates potential strategies utilized for inducing oncogenesis by these human gammaherpesviruses.
Topics: Carcinogenesis; Epigenesis, Genetic; Gammaherpesvirinae; Genome, Viral; Herpesviridae Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Tumor Virus Infections; Virus Latency
PubMed: 32991266
DOI: 10.1146/annurev-virology-020420-014025 -
International Journal of Molecular... Apr 2023Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer... (Review)
Review
Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, β-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.
Topics: Humans; SARS-CoV-2; Epstein-Barr Virus Infections; Papillomavirus Infections; Post-Acute COVID-19 Syndrome; Herpesvirus 4, Human; COVID-19; Neoplasms; Oncogenic Viruses; Cell Transformation, Neoplastic; Hepatitis C
PubMed: 37175509
DOI: 10.3390/ijms24097803 -
Cancer Discovery Jan 2023The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin...
UNLABELLED
The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, "low-risk" HPV, recapitulates the molecular hallmarks of oncogenic, "high-risk" HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell-like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell-like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.
SIGNIFICANCE
We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell-like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers. See related commentary by Starrett et al., p. 17. This article is highlighted in the In This Issue feature, p. 1.
Topics: Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Neoplasms; Skin Neoplasms; Bone Neoplasms; Breast Neoplasms; Papillomaviridae; Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Germ Cells
PubMed: 36213965
DOI: 10.1158/2159-8290.CD-22-0489 -
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 -
Biology Oct 2021Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and... (Review)
Review
Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and inhibiting apoptosis. They counteract the cellular antiviral defense through viral proteins as well as specific cellular effectors involved in virus-induced tumorigenesis. Type I interferons (IFNs) are a family of cytokines critical not only for viral interference but also for their broad range of properties that go beyond the antiviral action. In fact, they can inhibit cell proliferation and modulate differentiation, apoptosis, and migration. However, their principal role is to regulate the development and activity of most effector cells of the innate and adaptive immune responses. Various are the mechanisms by which IFNs exert their effects on immune cells. They can act directly, through IFN receptor triggering, or indirectly by the induction of chemokines, the secretion of further cytokines, or by the stimulation of cells useful for the activation of particular immune cells. All the properties of IFNs are crucial in the host defense against viruses and bacteria, as well as in the immune surveillance against tumors. IFNs may be affected by and, in turn, affect signaling pathways to mediate anti-proliferative and antiviral responses in virus-induced tumorigenic context. New data on cellular and viral microRNAs (miRNAs) machinery, as well as cellular communication and microenvironment modification via classical secretion mechanisms and extracellular vesicles-mediated delivery are reported. Recent research is reviewed on the tumorigenesis induced by specific viruses with RNA or DNA genome, belonging to different families (i.e., HPV, HTLV-1, MCPyV, JCPyV, Herpesviruses, HBV, HCV) and the IFN system involvement.
PubMed: 34681093
DOI: 10.3390/biology10100994 -
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 -
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