Traces the history of the study of tumor viruses and its role in driving breakthroughs in cancer research.Worldwide, approximately one-fifth of human cancers are caused by tumor viruses, with ...hepatitis B virus and HPV being the leading culprits. While the explosive growth in molecular biology in the late twentieth century is well known, the role that the study of tumor viruses has played in driving many of the greatest breakthroughs is not. Without the insights gained by studying tumor viruses, many significant theoretical advancements over the last four decades in cellular and molecular biology would not have been made. More practically, the study of tumor viruses has saved thousands, if not millions, of lives.In Cancer Virus Hunters, Gregory J. Morgan traces the high points in the development of tumor virology, from Peyton Rous's pioneering work on chicken tumors in 1909 to the successful development of an HPV vaccine for cervical cancer in 2006. Morgan offers a novel approach to understanding the interconnectedness of a long series of biomedical breakthroughs, including those that led to seven Nobel prizes. Among other advances, Morgan describes and contextualizes the science that prompted the discoveries of reverse transcriptase, RNA splicing, the tumor suppressor p53, the vaccine for hepatitis B, and the HIV test. He also explores how cancer virus hunters have demonstrated the virtue of beginning with a simple system, even when investigating a complex disease like cancer.Based on extensive archival research and over fifty interviews with experts, Cancer Virus Hunters is a tour de force summarizing a century of research to show how discoveries made with tumor viruses came to dominate the contemporary understanding of cancer. By showcasing the scientists themselves, the book makes for an unusually accessible journey through the history of science. It will be of interest to biomedical professionals—especially in oncology, hepatology, and infectious disease—in addition to historians of science and anyone interested in cancer research.
CXCR4 is involved in many facets of cancer, including being a major player in establishing metastasis. This is in part due to the deregulation of CXCR4, which can be attributed to many genetic and ...epigenetic mechanisms, including aberrant microRNA-CXCR4 interaction. MicroRNAs (miRNAs) are a type of small non-coding RNA that primarily targets the 3' UTR of mRNA transcripts, which in turn suppresses mRNA and subsequent protein expression. In this review, we reported and characterized the many aberrant miRNA-CXCR4 interactions that occur throughout human cancers. In particular, we reported known target sequences located on the 3' UTR of CXCR4 transcripts that tumour suppressor miRNAs bind and therefore regulate expression by. From these aberrant interactions, we also documented affected downstream genes/pathways and whether a particular tumour suppressor miRNA was reported as a prognostic marker in its respected cancer type. In addition, a limited number of cancer-causing miRNAs coined 'oncomirs' were reported and described in relation to CXCR4 regulation. Moreover, the mechanisms underlying both tumour suppressor and oncomir deregulations concerning CXCR4 expression were also explored. Furthermore, the miR-146a-CXCR4 axis was delineated in oncoviral infected endothelial cells in the context of virus-causing cancers. Lastly, miRNA-driven therapies and CXCR4 antagonist drugs were discussed as potential future treatment options in reported cancers pertaining to deregulated miRNA-CXCR4 interactions.
Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides ...oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the
subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, including proteins and non-coding RNAs, some of which have been shown to deregulate angiogenic pathways and promote tumor growth. In this review, we discuss the ability of both viruses to modulate the pro-angiogenic process.
Epstein–Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus ...(MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses.
Xipapillomavirus includes a group of viruses almost exclusively reported in both beef cattle and dairy breeding, in which they induce papillomatosis and occasionally malignant tumors. Bovine ...papillomaviruses (BPVs) infection impacts greatly on animal productions, and this is amplified by their cosmopolitan distribution. Cutaneous proliferative lesions in bovines can relate to leather depreciation and impaired milk production by giving rise to obstruction of the teat and hygiene limitations, often leading to hemorrhagic mastitis. This study reports the identification of a novel Xipapillomavirus type associated with udder papilloma in a Jersey cow in Costa Rica. Viral genome was fully sequenced and molecularly characterized. Histopathology and viral phylogeny and evolution are also presented and discussed by comparison with already described BPVs. Based on results, a novel Xipapillomavirus type, namely BPV30, is proposed. BPV30 is a typical Xipapillomavirus 2 most similar to BPV12, from which it separated roughly 18 million years ago. The absence of E6 and the presence of E10 in BPV30 confirm an E6 loss occurring along the clade leading to BPV12. The identification of this novel BPV is fundamental to the development of specific prophylactic tools, which represent the most effective weapon to fight viral circulation, to prevent infections, and eventually controlling associated proliferative lesions.
•A novel Xipapillomavirus (BPV30) was identified associated to cutaneous udder papilloma in cattle.•BPV30 genome has been fully sequenced and characterized and its evolutionary history fully reconstructed.•BPV30 evolution confirm the loss of E6 along the clade leading to BPV12.•This study is fundamental to development of tools to control bovine papillomatosis.
Abstract The advent of modern molecular biology has allowed for the discovery of several mechanisms by which oncoviruses promote carcinogenesis. Remarkably, nearly all human oncogenic viruses ...increase levels of the transcription factor hypoxia-inducible factor 1 (HIF-1). In this review, we highlight HIF-1׳s significance in viral oncogenesis, while providing an in-depth analysis of its activation mechanisms by the following oncoviruses: human papillomaviruses (HPVs), hepatitis B/C viruses (HBV/HCVs), Epstein–Barr virus (EBV), Kaposi׳s sarcoma-associated herpes virus (KSHV), and human T-cell lymphotropic virus (HTLV-1). We discuss virus-induced HIF-1׳s role in transcriptional upregulation of metabolic, angiogenic, and microenvironmental factors that are integral for oncogenesis. Admittedly, conclusive evidence is lacking as to whether activation of HIF-1 target genes is necessary for malignant transformation or merely a result thereof. In addition, a complete understanding of host–virus interactions, the effect of viral genomic variation, and the clinical (and potential therapeutic) relevance of HIF-1 in viral oncogenesis warrant further investigation.
Modelling the evolution of viral oncogenesis Murall, Carmen Lía; Alizon, Samuel
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
05/2019, Letnik:
374, Številka:
1773
Journal Article
Recenzirano
Odprti dostop
Most human oncogenic viruses share several characteristics, such as being DNA viruses, having long (co)evolutionary histories with their hosts and causing either latent or chronic infections. They ...can reach high prevalences while causing relatively low case mortality, which makes them quite fit according to virulence evolution theory. After analysing the life histories of DNA oncoviruses, we use a mathematical modelling approach to investigate how the virus life cycle may generate selective pressures favouring or acting against oncogenesis at the within-host or at the between-host level. In particular, we focus on two oncoprotein activities, namely extending cell life expectancy and increasing cell proliferation rate. These have immediate benefits (increasing viral population size) but can be associated with fitness costs at the epidemiological level (increasing recovery rate or risk of cancer) thus creating evolutionary trade-offs. We interpret the results of our nested model in light of the biological features and identify future perspectives for modelling oncovirus dynamics and evolution. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
Carcinogenic viruses (oncoviruses) can initiate cancer, but their impact on established cancer varies. Some of these viruses prolong survival while others shorten it. This study classifies ...oncoviruses into two categories: viruses which induce a strong CD8+T cell reaction in non-cancerous tissues, and viruses which induce a weak CD8+ T cell reaction in non-cancerous tissues. The classification proves useful in predicting the effect of oncoviruses on the prognosis of solid cancers. Therefore, while eliminating carcinogenic viruses in healthy individuals (for example by immunization) may be important for cancer prevention, this study suggests that only viruses which induce a weak CD8+ T cell reaction should be eradicated in established solid tumors. The model correctly predicts the effect of oncoviruses on survival for six out of seven known oncoviruses, indicating that immune modulation by oncoviruses has a prominent effect on prognosis. It seems that CD8+ T cell response to oncoviruses observed in infected benign tissues is retained in infected tumors. Clinical significance: the effect of oncoviruses on solid cancer prognosis can be predicted with confidence based on immunological responses when clinical data are unavailable.
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.
Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated ...cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.
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