-
Seminars in Cancer Biology Oct 2013Autophagy is a highly conserved and regulated process in eukaryotic cells by which components of the cytoplasm, such as damaged organelles and foreign pathogens, become... (Review)
Review
Autophagy is a highly conserved and regulated process in eukaryotic cells by which components of the cytoplasm, such as damaged organelles and foreign pathogens, become enveloped into double-membrane autophagosome vesicles that fuse with the lysosome for degradation. Viruses are adept at subverting host cellular pathways for their replication and survival. The human tumor viruses, Epstein-Barr virus (EBV), Kaposi's Sarcoma-Associated Herpesvirus (KSHV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV), have evolved novel ways of modulating autophagy during productive and latent stages of the virus life cycle. This review will discuss how the autophagy pathway becomes activated upon viral infection and the role of viral proteins in regulating the autophagy pathway. Specifically, we will examine how virus-encoded homologs of autophagy proteins evade autophagy-mediated degradation by blocking the induction, elongation, or maturation steps in the autophagy pathway. We will also discuss how certain viruses enhance autophagy induction or usurp autophagic machinery for their own replication. A comprehensive understanding of the autophagic response to tumor viruses may enable the discovery of novel antiviral and/or anticancer drug therapies.
Topics: Animals; Autophagy; Host-Pathogen Interactions; Humans; Oncogenic Viruses; Viral Proteins; Virus Replication
PubMed: 23727156
DOI: 10.1016/j.semcancer.2013.05.005 -
Cancer Research Oct 2008In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific... (Review)
Review
In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses--EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses--human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century.
Topics: Animals; Bird Diseases; Birds; Genes, Tumor Suppressor; History, 20th Century; History, 21st Century; Humans; Models, Biological; Neoplasms; Oncogenic Viruses; Virology; Virus Physiological Phenomena
PubMed: 18829521
DOI: 10.1158/0008-5472.CAN-08-3301 -
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 -
FEMS Microbiology Reviews Mar 2019Human γ-herpesviruses include the closely related tumor viruses Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). EBV is the most... (Review)
Review
Human γ-herpesviruses include the closely related tumor viruses Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). EBV is the most growth-transforming pathogen known and is linked to at least seven human malignancies. KSHV is also associated with three human cancers. Most EBV- and KSHV-infected individuals fortunately remain disease-free despite persistent infection and this is likely due to the robustness of the immune control that they mount against these tumor viruses. However, upon immune suppression EBV- and KSHV-associated malignancies emerge at increased frequencies. Moreover, primary immunodeficiencies with individual mutations that predispose to EBV or KSHV disease allow us to gain insights into a catalog of molecules that are required for the immune control of these tumor viruses. Curiously, there is little overlap between the mutation targets that predispose individuals to EBV versus KSHV disease, even so both viruses can infect the same host cell, human B cells. These differences will be discussed in this review. A better understanding of the crucial components in the near-perfect life-long immune control of EBV and KSHV should allow us to target malignancies that are associated with these viruses, but also induce similar immune responses against other tumors.
Topics: Genetic Predisposition to Disease; Herpesviridae; Herpesvirus 4, Human; Herpesvirus 8, Human; Host-Pathogen Interactions; Humans; Immunocompetence; Immunologic Deficiency Syndromes; Neoplasms; Oncogenic Viruses
PubMed: 30649299
DOI: 10.1093/femsre/fuy044 -
Current Topics in Microbiology and... 2013Viruses encounter many challenges within host cells in order to replicate their nucleic acid. In the case of DNA viruses, one challenge that must be overcome is... (Review)
Review
Viruses encounter many challenges within host cells in order to replicate their nucleic acid. In the case of DNA viruses, one challenge that must be overcome is recognition of viral DNA structures by the host DNA damage response (DDR) machinery. This is accomplished in elegant and unique ways by different viruses as each has specific needs and sensitivities dependent on its life cycle. In this review, we focus on three DNA tumor viruses and their interactions with the DDR. The viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) account for nearly all of the virus-associated human cancers worldwide. These viruses have also been excellent models for the study of oncogenic virus-mediated cell transformation. In this review, we will discuss how each of these viruses engage and subvert aspects of the host DDR. The first level of DDR engagement is a result of the genetic linkage between the oncogenic potential of these viruses and their ability to replicate. Namely, the promotion of cells from quiescence into the cell cycle to facilitate virus replication can be sensed through aberrant cellular DNA replication structures which activate the DDR and hinder cell transformation. DNA tumor viruses subvert this growth-suppressive DDR through changes in viral oncoprotein expression which ultimately facilitate virus replication. An additional level of DDR engagement is through direct detection of replicating viral DNA. These interactions parallel those observed in other DNA virus systems in that the need to subvert these intrinsic sensors of aberrant DNA structure in order to replicate must be in place. DNA tumor viruses are no exception. This review will cover the molecular features of DNA tumor virus interactions with the host DDR and the consequences for virus replication.
Topics: Animals; DNA Damage; DNA Tumor Viruses; Humans; Tumor Virus Infections; Virus Replication
PubMed: 23686238
DOI: 10.1007/978-3-642-37765-5_9 -
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 -
California Medicine May 1965The answer to the important question, "Do viruses play a role in human cancer?" is still unknown. Although many scientists think that they may play a role,... (Review)
Review
The answer to the important question, "Do viruses play a role in human cancer?" is still unknown. Although many scientists think that they may play a role, straightforward attempts to isolate human tumor viruses in animals or in tissue cultures have failed. Possibly the most sensitive test object, newborn human infants, of course cannot be used as test objects, and this may explain the failure to isolate human tumor viruses. At present, it would appear that the best means of tackling the problem of viral-induced carcinogenesis is to study the basic characteristics of known tumor viruses and the basic aspects of their interactions with cells. Both RNA-containing and DNA-containing viruses, two obviously different classes of virus, can cause cancer and therefore both classes must be studied in order to obtain a complete picture of the role of viruses in causing cancer in animals and cell transformation in vitro. Such basic studies already have yielded information of great importance to general biology.A number of exciting developments have occurred in the area of virus-induced cancer. One of these is the oncogenic capacity in hamsters of certain human adenoviruses, and an intensive probe of their possible role in human cancer is in progress. Another is the detection by electron microscopy of virus-like particles in the tissues and serum of patients with leukemia. Rigid criteria have been suggested to establish etiologic significance of viruses recovered from human cancer tissues and of the virus-like particles observed by electron microscopy in serum or malignant tissues from cancer patients. If viruses are eventually found to play a role in human cancer, then perhaps the disease can be prevented by vaccines and treated with antiviral substances.
Topics: Adenoviruses, Human; Animals; Cell Transformation, Neoplastic; Cricetinae; DNA Viruses; Humans; Microscopy, Electron; Neoplasms; Oncogenic Viruses; Viruses
PubMed: 14290931
DOI: No ID Found -
Biochemistry. Biokhimiia Oct 2020The disruption of apoptotic cell death process is closely associated with the etiology of various diseases, including cancer. Permanent viral infections can cause... (Review)
Review
The disruption of apoptotic cell death process is closely associated with the etiology of various diseases, including cancer. Permanent viral infections can cause different types of cancers. Oncogenic viruses manipulate both external and internal apoptosis pathways, and inhibit the activity of proapoptotic proteins and signaling pathways, which facilitates carcinogenesis. Ineffective immune surveillance or immune response suppression can induce uncontrolled virus propagation and host cell proliferation. In this review, we discuss current data that provide insights into mechanisms of apoptotic death suppression by viruses and their role in oncogenesis.
Topics: Apoptosis; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation; Humans; Mitochondria; NF-kappa B; Oncogenic Viruses; Phosphatidylinositol 3-Kinases; Tumor Suppressor Protein p53; Tumor Virus Infections
PubMed: 33202204
DOI: 10.1134/S0006297920100077 -
Tumour Virus Research Jun 2022Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis... (Review)
Review
Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis with a low survival rate of 15-25%. Depending upon the cell type, oesophageal carcinoma is categorised into oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC). ESCC is predominantly reported in developing countries, while EAC is more common in developed countries. Aside from the presence of exogenous co-factors, such as cigarette smoking, alcohol consumption, obesity, gastroesophageal reflux disease (GERD); infection with oncogenic viruses is suspected to be one of the major factors contributing to EC development. Oncogenic viruses, including human papillomavirus (HPV), Epstein Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) have been detected in various proportions of EC samples. Nonetheless, their aetiological roles in EC remain debatable. In this review, we garnered previous studies that focus on the association between oncogenic viruses and EC. Among these oncogenic viruses, HPV appears to have a stronger association with EC than the others. In addition, we also discuss the pros and cons of the treatment regimens to treat EC patients, including immunotherapy, chemo- and chemoradiotherapy, and their efficacy.
Topics: Alphapapillomavirus; Carcinoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 34920177
DOI: 10.1016/j.tvr.2021.200231 -
Philosophical Transactions of the Royal... Oct 2017With the advent of massively parallel sequencing, oncogenic viruses in tumours can now be detected in an unbiased and comprehensive manner. Additionally, new viruses or... (Review)
Review
With the advent of massively parallel sequencing, oncogenic viruses in tumours can now be detected in an unbiased and comprehensive manner. Additionally, new viruses or strains can be discovered based on sequence similarity with known viruses. Using this approach, the causative agent for Merkel cell carcinoma was identified. Subsequent studies using data from large collections of tumours have confirmed models built during decades of hypothesis-driven and low-throughput research, and a more detailed and comprehensive description of virus-tumour associations have emerged. Notably, large cohorts and high sequencing depth, in combination with newly developed bioinformatical techniques, have made it possible to rule out several suggested virus-tumour associations with a high degree of confidence. In this review we discuss possibilities, limitations and insights gained from using massively parallel sequencing to characterize tumours with viral content, with emphasis on detection of viral sequences and genomic integration events.This article is part of the themed issue 'Human oncogenic viruses'.
Topics: DNA, Viral; Genomics; High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Oncogenic Viruses; RNA, Viral; Sequence Analysis, DNA; Sequence Analysis, RNA; Tumor Virus Infections
PubMed: 28893932
DOI: 10.1098/rstb.2016.0265