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International Journal of Molecular... Jul 2021Globally, HIV/AIDS and cancer are increasingly public health problems and continue to exist as comorbidities. The sub-Saharan African region has the largest number of... (Review)
Review
Globally, HIV/AIDS and cancer are increasingly public health problems and continue to exist as comorbidities. The sub-Saharan African region has the largest number of HIV infections. Malignancies previously associated with HIV/AIDS, also known as the AIDS-defining cancers (ADCs) have been documented to decrease, while the non-AIDS defining cancer (NADCs) are on the rise. On the other hand, cancer is a highly heterogeneous disease and precision oncology as the most effective cancer therapy is gaining attraction. Among HIV-infected individuals, the increased risk for developing cancer is due to the immune system of the patient being suppressed, frequent coinfection with oncogenic viruses and an increase in risky behavior such as poor lifestyle. The core of personalised medicine for cancer depends on the discovery and the development of biomarkers. Biomarkers are specific and highly sensitive markers that reveal information that aid in leading to the diagnosis, prognosis and therapy of the disease. This review focuses mainly on the risk assessment, diagnostic, prognostic and therapeutic role of various cancer biomarkers in HIV-positive patients. A careful selection of sensitive and specific HIV-associated cancer biomarkers is required to identify patients at most risk of tumour development, thus improving the diagnosis and prognosis of the disease.
Topics: Acquired Immunodeficiency Syndrome; Antiretroviral Therapy, Highly Active; Biomarkers, Tumor; Comorbidity; Early Detection of Cancer; Female; HIV-1; Humans; Male; Neoplasms; Oncogenic Viruses; Precision Medicine; Prevalence; Prognosis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 34360891
DOI: 10.3390/ijms22158127 -
Trends in Microbiology Feb 2020The human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) share the common property of... (Review)
Review
The human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) share the common property of persisting as multicopy episomes in the nuclei of rapidly dividing host cells. These episomes form the molecular basis for viral latency and are etiologically linked to virus-associated cancers. Episome maintenance requires epigenetic programming to ensure the proper control of viral gene expression, DNA replication, and genome copy number. For these viruses, episome maintenance requires a dedicated virus-encoded episome maintenance protein (EMP), namely LANA (KSHV), EBNA1 (EBV), and E2 (HPV). Here, we review common features of these viral EMPs and discuss recent advances in understanding how they contribute to the epigenetic control of viral episome maintenance during latency.
Topics: Alphapapillomavirus; Epigenesis, Genetic; Genome, Viral; Herpesvirus 4, Human; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Plasmids; Protein Domains; Viral Proteins; Virus Latency; Virus Replication
PubMed: 31624007
DOI: 10.1016/j.tim.2019.09.002 -
Viruses Jul 2022Human papillomavirus type 16 (HPV 16) is the most common oncogenic type of HPV in cervical, anogenital, and head and neck cancers, making HPV 16 an important high-risk... (Review)
Review
Human papillomavirus type 16 (HPV 16) is the most common oncogenic type of HPV in cervical, anogenital, and head and neck cancers, making HPV 16 an important high-risk HPV (HR HPV) type. To create an environment permissible for viral maintenance and growth and to initiate and support oncogenesis, the HR HPV protein E6 functions to dysregulate normal cellular processes. HR HPV type 16 E6 (16E6) has previously been shown to bind cellular proteins in order to transcriptionally activate genes and to target regulatory proteins for degradation. We have identified an additional functional model for 16E6. First, 16E6 binds to cellular RNA processing and binding proteins, specifically cytoplasmic poly(A) binding proteins (PABPCs) and NFX1-123. Then, 16E6 hijacks those proteins' functions to post-transcriptionally regulate cellular immortalization, growth, and differentiation genes and pathways in keratinocytes. In this review, we have highlighted studies that introduce this new model of 16E6 functionality. Understanding ways in which HR HPV dysregulates cellular processes-particularly at the level of post-transcriptional gene regulation-presents new ways to consider mechanisms underlying DNA tumor virus function and new areas for therapeutic target development in HPV-associated cancers.
Topics: Gene Expression Regulation; Host Microbial Interactions; Human papillomavirus 16; Humans; Keratinocytes; Oncogene Proteins, Viral; Papillomavirus Infections
PubMed: 35891463
DOI: 10.3390/v14071483 -
Viruses Mar 2023Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous... (Review)
Review
Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been implicated in promoting this persistence. The precursor of hepatitis e antigen (HBeAg), is translated from the precore/core region and is post-translationally modified to yield HBeAg, which is secreted in the serum. HBeAg is a non-particulate protein of HBV and can act as both a tolerogen and an immunogen. HBeAg can protect hepatocytes from apoptosis by interfering with host signalling pathways and acting as a decoy to the immune response. By evading the immune response and interfering with apoptosis, HBeAg has the potential to contribute to the hepatocarcinogenic potential of HBV. In particular, this review summarises the various signalling pathways through which HBeAg and its precursors can promote hepatocarcinogenesis via the various hallmarks of cancer.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B e Antigens; Liver Neoplasms; Hepatitis B virus; Hepatitis B; Hepatitis B, Chronic; Mutation; DNA, Viral
PubMed: 37112837
DOI: 10.3390/v15040857 -
Med (New York, N.Y.) Jun 2023The majority of oncogenic viruses are capable of integrating into the host genome, posing significant challenges to clinical control. Recent conceptual and technological...
The majority of oncogenic viruses are capable of integrating into the host genome, posing significant challenges to clinical control. Recent conceptual and technological advances, however, offer promising clinical applications. Here, we summarize the advances in our understanding of oncogenic viral integration, their clinical relevance, and the future perspectives.
Topics: Oncogenic Viruses; Genome; Virus Integration
PubMed: 37301195
DOI: 10.1016/j.medj.2023.04.007 -
Advances in Virus Research 2021The DNA viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are members of the gammaherpesvirus subfamily, a group of viruses whose... (Review)
Review
The DNA viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are members of the gammaherpesvirus subfamily, a group of viruses whose infection is associated with multiple malignancies, including cancer. The primary host for these viruses is humans and, like all herpesviruses, infection with these pathogens is lifelong. Due to the persistence of gammaherpesvirus infection and the potential for cancer formation in infected individuals, there is a driving need to understand not only the biology of these viruses and how they remain undetected in host cells but also the mechanism(s) by which tumorigenesis occurs. One of the methods that has provided much insight into these processes is proteomics. Proteomics is the study of all the proteins that are encoded by a genome and allows for (i) identification of existing and novel proteins derived from a given genome, (ii) interrogation of protein-protein interactions within a system, and (iii) discovery of druggable targets for the treatment of malignancies. In this chapter, we explore how proteomics has contributed to our current understanding of gammaherpesvirus biology and their oncogenic processes, as well as the clinical applications of proteomics for the detection and treatment of gammaherpesvirus-associated cancers.
Topics: Books; Carcinogenesis; DNA Viruses; Gammaherpesvirinae; Herpesviridae Infections; Host Microbial Interactions; Humans; Proteomics; Tumor Virus Infections; Virus Replication
PubMed: 33934828
DOI: 10.1016/bs.aivir.2020.10.001 -
International Journal of Molecular... Nov 2022The development of cancer is a multifactorial phenomenon, while it constitutes a major global health problem. Viruses are an important factor that is involved in... (Review)
Review
The development of cancer is a multifactorial phenomenon, while it constitutes a major global health problem. Viruses are an important factor that is involved in tumorigenesis and is associated with 12.1% of all cancer cases. Major examples of oncogenic viruses which are closely associated with the digestive system are HBV, HCV, EBV, HPV, JCV, and CMV. EBV, HPV, JCV, and CMV directly cause oncogenesis by expressing oncogenic proteins that are encoded in their genome. In contrast, HBV and HCV are correlated indirectly with carcinogenesis by causing chronic inflammation in the infected organs. In addition, the tumor microenvironment contains various immune cells, endothelial cells, and fibroblasts, as well as several growth factors, cytokines, and other tumor-secreted molecules that play a key role in tumor growth, progression, and migration, while they are closely interrelated with the virus. The presence of T-regulatory and B-regulatory cells in the tumor microenvironment plays an important role in the anti-tumor immune reaction. The tumor immune microenvironments differ in each type of cancer and depend on viral infection. The alterations in the immune microenvironment caused by viruses are also reflected in the effectiveness of immunotherapy. The present review aims at shedding light on the association between viruses and digestive system malignancies, the characteristics of the tumor immune microenvironment that develop, and the possible treatments that can be administered.
Topics: Humans; Endothelial Cells; Papillomavirus Infections; Tumor Microenvironment; Gastrointestinal Neoplasms; Carcinogenesis; Immunotherapy; Cell Transformation, Neoplastic; Cytomegalovirus Infections; Hepatitis C
PubMed: 36362398
DOI: 10.3390/ijms232113612 -
Viruses May 2021The success of long-term host-virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus's skill in... (Review)
Review
The success of long-term host-virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus's skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silently in their hosts, though perturbations in this host-virus equilibrium can result in disease. The heterochromatin machinery that tightly regulates endogenous retroviral elements and pericentromeric repeats also silences invading genomes of alpha-, beta-, and gammaherpesviruses. That said, how these viruses disrupt this constitutive heterochromatin machinery to replicate and spread, particularly in response to disparate lytic triggers, is unclear. Here, we review how the cancer-causing gammaherpesvirus Epstein-Barr virus (EBV) uses the inflammasome as a security system to alert itself of threats to its cellular home as well as to flip the virus-encoded lytic switch, allowing it to replicate and escape in response to a variety of lytic triggers. EBV provides the first example of an infectious agent able to actively exploit the inflammasome to spark its replication. Revealing an unexpected link between the inflammasome and the epigenome, this further brings insights into how the heterochromatin machinery uses differential strategies to maintain the integrity of the cellular genome whilst guarding against invading pathogens. These recent insights into EBV biology and host-viral epigenetic regulation ultimately point to the NLRP3 inflammasome as an attractive target to thwart herpesvirus reactivation.
Topics: Carcinogenesis; Cell Line, Tumor; Epigenesis, Genetic; Epstein-Barr Virus Infections; Herpesviridae; Herpesvirus 4, Human; Heterochromatin; Humans; Inflammasomes; Virus Activation; Virus Latency; Virus Replication
PubMed: 34066537
DOI: 10.3390/v13050846 -
Cureus Sep 2019Multiple sclerosis (MS) is a chronic neuro-inflammatory, immune-mediated disorder of the central nervous system; however, less is known about its cause. It causes... (Review)
Review
Multiple sclerosis (MS) is a chronic neuro-inflammatory, immune-mediated disorder of the central nervous system; however, less is known about its cause. It causes neurological disability in young adults, more commonly in women. Several risk factors including environmental, genetics, and infections have been identified, which contribute to the abnormal immune response. Viruses belonging to the Herpes family have been indicated as a potential risk for MS; their biological mechanisms are not known but several possibilities have been discussed. Epstein-Barr virus (EBV) is the leading and most common virus associated with MS. It is a potential oncogenic virus that hosts the B lymphocytes and has been associated with numerous cancers such as Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma. The risk of MS is low in patients who are EBV negative but increases by several folds in individuals who have a history of infectious mononucleosis (IM). Several ecological studies, co-occurring pathologies, and experimental laboratory-based research provide evidence to support the relationship between EBV and MS.
PubMed: 31720167
DOI: 10.7759/cureus.5699 -
RNA Biology May 2021Oncogenic viruses are associated with approximately 15% of human cancers. In viral infections, microRNAs play an important role in host-pathogen interactions. miR-21 is... (Review)
Review
Oncogenic viruses are associated with approximately 15% of human cancers. In viral infections, microRNAs play an important role in host-pathogen interactions. miR-21 is a highly conserved non-coding RNA that not only regulates the development of oncogenic viral diseases, but also responds to the regulation of intracellular signal pathways. Oncogenic viruses, including HBV, HCV, HPV, and EBV, co-evolve with their hosts and cause persistent infections. The upregulation of host miR-21 manipulates key cellular pathways to evade host immune responses and then promote viral replication. Thus, a better understanding of the role of miR-21 in viral infections may help us to develop effective genetically-engineered oncolytic virus-based therapies against cancer.
Topics: Animals; Host-Pathogen Interactions; Humans; MicroRNAs; Neoplasms; Oncogenic Viruses; Tumor Virus Infections; Virus Replication
PubMed: 33499700
DOI: 10.1080/15476286.2021.1880756