-
Seminars in Immunology Aug 2017During the last few decades we have become accustomed to the idea that viruses can cause tumors. It is much less considered and discussed, however, that most people... (Review)
Review
During the last few decades we have become accustomed to the idea that viruses can cause tumors. It is much less considered and discussed, however, that most people infected with oncoviruses will never develop cancer. Therefore, the genetic and environmental factors that tip the scales from clearance of viral infection to development of cancer are currently an area of active investigation. Microbiota has recently emerged as a potentially critical factor that would affect this balance by increasing or decreasing the ability of viral infection to promote carcinogenesis. In this review, we provide a model of microbiome contribution to the development of oncogenic viral infections and viral associated cancers, give examples of this process in human tumors, and describe the challenges that prevent progress in the field as well as their potential solutions.
Topics: Animals; Carcinogenesis; Gene-Environment Interaction; Humans; Microbiota; Neoplasms; Oncogenic Viruses; Viral Load; Virus Diseases
PubMed: 28602713
DOI: 10.1016/j.smim.2017.05.003 -
Virology Journal Jun 2013Transforming viruses can change a normal cell into a cancer cell during their normal life cycle. Persistent infections with these viruses have been recognized to cause... (Review)
Review
Transforming viruses can change a normal cell into a cancer cell during their normal life cycle. Persistent infections with these viruses have been recognized to cause some types of cancer. These viruses have been implicated in the modulation of various biological processes, such as proliferation, differentiation and apoptosis. The study of infections caused by oncogenic viruses had helped in our understanding of several mechanisms that regulate cell growth, as well as the molecular alterations leading to cancer. Therefore, transforming viruses provide models of study that have enabled the advances in cancer research. Viruses with transforming abilities, include different members of the Human Papillomavirus (HPV) family, Hepatitis C virus (HCV), Human T-cell Leukemia virus (HTLV-1), Epstein Barr virus (EBV) and Kaposi's Sarcoma Herpesvirus (KSHV).Apoptosis, or programmed cell death, is a tightly regulated process that plays an important role in development and homeostasis. Additionally, it functions as an antiviral defense mechanism. The deregulation of apoptosis has been implicated in the etiology of diverse diseases, including cancer. Oncogenic viruses employ different mechanisms to inhibit the apoptotic process, allowing the propagation of infected and damaged cells. During this process, some viral proteins are able to evade the immune system, while others can directly interact with the caspases involved in apoptotic signaling. In some instances, viral proteins can also promote apoptosis, which may be necessary for an accurate regulation of the initial stages of infection.
Topics: Apoptosis; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Oncogenic Viruses
PubMed: 23741982
DOI: 10.1186/1743-422X-10-182 -
Viruses Sep 2022Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to... (Review)
Review
Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses initially infect DCs and propagate the infection to CD4 T cells through cell-to-cell transmission using mechanisms including the formation of virologic synapses, viral biofilms, and conduits. These retroviruses are both neurotrophic with neurovirulence determinants. The neuropathogenesis of HIV-1 and HTLV-1 results in neurodegenerative diseases such as HIV-associated neurocognitive disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Infected DCs are known to traffic to the brain (CNS) and periphery (PNS, lymphatics) to induce neurodegeneration in HAND and HAM/TSP patients. Elevated levels of neuroinflammation have been correlated with cognitive decline and impairment of motor control performance. Current vaccinations and therapeutics for HIV-1 and HTLV-1 are assessed and can be applied to patients with HIV-1-associated cancers and adult T cell leukemia/lymphoma (ATL). These diseases caused by co-infections can result in both neurodegeneration and cancer. There are associations with cancer malignancies and HIV-1 and HTLV-1 as well as other human oncogenic viruses (EBV, HBV, HCV, HDV, and HPV). This review contains current knowledge on DC sensing of HIV-1 and HTLV-1 including DC-SIGN, Tat, Tax, and current viral therapies. An overview of DC interaction with oncogenic viruses including EBV, Hepatitis viruses, and HPV is also provided. Vaccines and therapeutics targeting host-pathogen interactions can provide a solution to co-infections, neurodegeneration, and cancer.
Topics: Adult; Coinfection; Dendritic Cells; HIV Infections; HIV Seropositivity; HIV-1; HTLV-I Infections; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Neoplasms; Oncogenic Viruses; Papillomavirus Infections; Paraparesis, Tropical Spastic
PubMed: 36146843
DOI: 10.3390/v14092037 -
British Journal of Cancer Jan 2012The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene... (Review)
Review
The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation.
Topics: Cell Transformation, Neoplastic; Cell Transformation, Viral; DNA Damage; Genes, cdc; Humans; Oncogenic Viruses; Tumor Virus Infections
PubMed: 22240795
DOI: 10.1038/bjc.2011.612 -
Journal of Molecular Biology Sep 2018The central importance of cell polarity control is emphasized by the frequency with which it is targeted by many diverse viruses. It is clear that in targeting key... (Review)
Review
The central importance of cell polarity control is emphasized by the frequency with which it is targeted by many diverse viruses. It is clear that in targeting key polarity control proteins, viruses affect not only host cell polarity, but also influence many cellular processes, including transcription, replication, and innate and acquired immunity. Examination of the interactions of different virus proteins with the cell and its polarity controls during the virus life cycles, and in virally-induced cell transformation shows ever more clearly how intimately all cellular processes are linked to the control of cell polarity.
Topics: Cell Polarity; Host-Pathogen Interactions; Humans; Immunity; Oncogenic Viruses; Organ Specificity; Virus Physiological Phenomena
PubMed: 29680664
DOI: 10.1016/j.jmb.2018.04.016 -
Virology Journal Jan 2021Viral oncogenic transformation of healthy cells into a malignant state is a well-established phenomenon but took decades from the discovery of tumor-associated viruses... (Review)
Review
Viral oncogenic transformation of healthy cells into a malignant state is a well-established phenomenon but took decades from the discovery of tumor-associated viruses to their accepted and established roles in oncogenesis. Viruses cause ~ 15% of know cancers and represents a significant global health burden. Beyond simply causing cellular transformation into a malignant form, a number of these cancers are augmented by a subset of viral factors that significantly enhance the tumor phenotype and, in some cases, are locked in a state of oncogenic addiction, and substantial research has elucidated the mechanisms in these cancers providing a rationale for targeted inactivation of the viral components as a treatment strategy. In many of these virus-associated cancers, the prognosis remains extremely poor, and novel drug approaches are urgently needed. Unlike non-specific small-molecule drug screens or the broad-acting toxic effects of chemo- and radiation therapy, the age of designer nucleases permits a rational approach to inactivating disease-causing targets, allowing for permanent inactivation of viral elements to inhibit tumorigenesis with growing evidence to support their efficacy in this role. Although many challenges remain for the clinical application of designer nucleases towards viral oncogenes; the uniqueness and clear molecular mechanism of these targets, combined with the distinct advantages of specific and permanent inactivation by nucleases, argues for their development as next-generation treatments for this aggressive group of cancers.
Topics: Animals; Carcinogenesis; Cell Line; Cell Transformation, Neoplastic; Cell Transformation, Viral; Humans; Mice; Neoplasms; Oncogenes; Oncogenic Viruses
PubMed: 33441159
DOI: 10.1186/s12985-021-01488-1 -
Philosophical Transactions of the Royal... May 2019One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention...
One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention through immunization against the viral infection, for early screening through molecular detection of the infectious agent, and potentially for specific treatments, by targeting the virus as a marker of cancer cells. Accomplishing these objectives will require a detailed understanding of the natural history of infections, the mechanisms by which the viruses contribute to disease, the mutual adaptation of viruses and hosts, and the possible viral evolution in the absence and in the presence of the public health interventions conceived to target them. This issue showcases the current developments in experimental tissue-like and animal systems, mathematical models and evolutionary approaches to understand DNA oncoviruses. Our global aim is to provide proximate explanations to the present-day interface and interactions between virus and host, as well as ultimate explanations about the adaptive value of these interactions and about the evolutionary pathways that have led to the current malignant phenotype of oncoviral infections. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
Topics: Animals; DNA Virus Infections; DNA Viruses; Evolution, Molecular; Humans; Oncogenic Viruses; Tumor Virus Infections; Virulence
PubMed: 30955496
DOI: 10.1098/rstb.2019.0041 -
Current Topics in Microbiology and... 2011NF-κB is a pivotal transcription factor that controls cell survival and proliferation in diverse physiological processes. The activity of NF-κB is tightly controlled... (Review)
Review
NF-κB is a pivotal transcription factor that controls cell survival and proliferation in diverse physiological processes. The activity of NF-κB is tightly controlled through its cytoplasmic sequestration by specific inhibitors, IκBs. Various cellular stimuli induce the activation of an IκB kinase, which phosphorylates IκBs and triggers their proteasomal degradation, causing nuclear translocation of activated NF-κB. Under normal conditions, the activation of NF-κB occurs transiently, thus ensuring rapid but temporary induction of target genes. Deregulated NF-κB activation contributes to the development of various diseases, including cancers and immunological disorders. Accumulated studies demonstrate that the NF-κB signaling pathway is a target of several human oncogenic viruses, including the human T cell leukemia virus type 1, the Kaposi sarcoma-associated herpesvirus, and the Epstein-Bar virus. These viruses encode specific oncoproteins that target different signaling components of the NF-κB pathway, leading to persistent activation of NF-κB. This chapter will discuss the molecular mechanisms by which NF-κB is activated by the viral oncoproteins.
Topics: Animals; Herpesvirus 4, Human; Herpesvirus 8, Human; Human T-lymphotropic virus 1; Humans; NF-kappa B; Oncogene Proteins, Viral; Signal Transduction
PubMed: 20845110
DOI: 10.1007/82_2010_108 -
Current Opinion in Virology Oct 2018Most humans are infected with at least one of the known human cancer viruses during their lifetimes. While the initial infection with these viruses does not cause major... (Review)
Review
Most humans are infected with at least one of the known human cancer viruses during their lifetimes. While the initial infection with these viruses does not cause major disease, infected cells can acquire cancer hallmarks, particularly upon immunosuppression or exposure to co-carcinogenic stimuli. Even though cancer formation represents a rare outcome of a viral infection, approximately one out of eight human cancers has a viral etiology. Viral cancers present unique opportunities for prophylaxis, diagnosis, and therapy, as demonstrated by the success of HBV and HPV vaccines and HCV antivirals in decreasing the incidence of tumors that are caused by these viruses. Here we review common characteristics and mechanisms of action of the human oncogenic viruses.
Topics: Animals; Carcinogenesis; Cell Transformation, Neoplastic; Humans; Immunocompromised Host; Mice; Neoplasms; Oncogenes; Oncogenic Viruses; Tumor Virus Infections; Vaccination; Virus Diseases
PubMed: 30268926
DOI: 10.1016/j.coviro.2018.09.003 -
Molekuliarnaia Biologiia 2019Numerous studies on the nature of neoplastic growth have demonstrated that oncogenic viruses maybe one of the factors causing cancer. According to various estimates,... (Review)
Review
Numerous studies on the nature of neoplastic growth have demonstrated that oncogenic viruses maybe one of the factors causing cancer. According to various estimates, 10-20% of all human cancers are caused by viruses. For example, the Epstein-Barr virus (EBV), hepatitis B and C viruses, human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV-1), human herpesvirus type 8 (HHV-8), and Merkel cell polyomavirus were implicated in initiating tumors. At the same time, the long period between viral infection and the manifestation of cancer significantly complicates the search for a causal relationship between the presence of a virus in the human organism and the malignant transformation. For this reason, the role of certain viruses in the initiation of neoplastic processes in humans remains an unresolved issue.
Topics: Cell Transformation, Neoplastic; Humans; Neoplasms; Oncogenic Viruses; Virus Diseases
PubMed: 31661485
DOI: 10.1134/S0026898419050033