-
Seminars in Diagnostic Pathology Jul 2018Immunosuppression induced by chronic medication, such as occurs post-transplantation, may increase a patient's risk of developing solid tumors. These are often rare... (Review)
Review
Immunosuppression induced by chronic medication, such as occurs post-transplantation, may increase a patient's risk of developing solid tumors. These are often rare tumors characterized by odd presentations. This review focuses on commonly encountered iatrogenic, non-hematopoietic solid tumors following immunotherapy and provides a practical approach to their diagnosis. All of the malignancies covered in this review are viral-induced. They include human papillomavirus (HPV)-associated carcinomas, Epstein-Barr virus (EBV)-associated tumors, Merkel cell polyomavirus (MCPyV)-related Merkel cell carcinoma, and Human Herpesvirus 8 (HHV8)-related Kaposi sarcoma. The complementary diagnostic role of ancillary studies, such as immunohistochemistry and in-situ hybridization that target these oncogenic viruses, is addressed.
Topics: Carcinoma, Merkel Cell; Herpesvirus 8, Human; Humans; Iatrogenic Disease; Immunohistochemistry; Immunosuppression Therapy; Immunotherapy; In Situ Hybridization; Papillomaviridae; Papillomavirus Infections; Sarcoma, Kaposi; Soft Tissue Neoplasms
PubMed: 29066044
DOI: 10.1053/j.semdp.2017.09.002 -
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 -
Philosophical Transactions of the Royal... Oct 2017Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now... (Review)
Review
Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: Herpesvirus 8, Human; Humans; Sarcoma, Kaposi
PubMed: 28893942
DOI: 10.1098/rstb.2016.0275 -
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 -
Viruses Oct 2014The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt's... (Review)
Review
The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt's lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.
Topics: Apoptosis; Cell Transformation, Neoplastic; Genomic Instability; Humans; Immune Tolerance; Neoplasms; Oncogenic Viruses; Tumor Virus Infections
PubMed: 25341666
DOI: 10.3390/v6104047 -
Papillomavirus Research (Amsterdam,... Jun 2019Over the last two decades many host cell proteins have been described to be involved in the process of infectious entry of oncogenic human papillomaviruses (HPV). After... (Review)
Review
Over the last two decades many host cell proteins have been described to be involved in the process of infectious entry of oncogenic human papillomaviruses (HPV). After initial binding and priming of the capsid, a sequence of events on the cell surface precedes the formation of the HPV entry platform. It has been shown that the virus-associated entry complex consists of membrane organizers, tetraspanins CD151 and CD63, and their associated partner proteins such as integrins, growth factor receptors, and the annexin A2 heterotetramer. Further recruitment of cytoplasmic factors such as the obscurin-like protein 1 and actin results in a non-canonical clathrin-independent endocytosis of the virus. Internalized viruses are then routed to multivesicular bodies for capsid disassembly. This early trafficking again involves annexins, and tetraspanin proteins. In this review, we summarize the current knowledge about HPV16 endocytosis and the subsequent endosomal trafficking. Moreover, we propose a model on how tetraspanins and annexins organize the spatial accumulation of HPV16-associated molecules, the recruitment of cytoplasmic trafficking factors, and the L2 membrane penetration to trigger virus entry.
Topics: Biological Transport; Endocytosis; Host-Pathogen Interactions; Human papillomavirus 16; Humans; Papillomavirus Infections; Virus Internalization
PubMed: 30946955
DOI: 10.1016/j.pvr.2019.03.004 -
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