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Current Opinion in Virology Oct 2015Any one model system, be it culture or animal, only recapitulates one aspect of the viral life cycle in the human host. By providing recent examples of animal models for... (Review)
Review
Any one model system, be it culture or animal, only recapitulates one aspect of the viral life cycle in the human host. By providing recent examples of animal models for Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus, we would argue that multiple animal models are needed to gain a comprehensive understanding of the pathogenesis associated with human oncogenic herpesviruses. Transgenic mice, homologous animal herpesviruses, and tumorgraft and humanized mouse models all complement each other in the study of viral pathogenesis. The use of animal model systems facilitates the exploration of novel anti-viral and anti-cancer treatment modalities for diseases associated with oncogenic herpesviruses.
Topics: Animals; Carcinogenesis; Disease Models, Animal; Herpesviridae; Herpesviridae Infections; Host-Pathogen Interactions; Humans; Mice; Oncogenic Viruses
PubMed: 26476352
DOI: 10.1016/j.coviro.2015.09.006 -
Molecular Pharmaceutics Aug 2023Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways... (Review)
Review
Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Carcinogenesis; Neoplasms; Antiviral Agents
PubMed: 37486263
DOI: 10.1021/acs.molpharmaceut.2c01080 -
British Journal of Hospital Medicine... Oct 2016Virus infections are an important factor in the global burden of human cancer. The discovery and mode of action of human tumour viruses is briefly reviewed together with... (Review)
Review
Virus infections are an important factor in the global burden of human cancer. The discovery and mode of action of human tumour viruses is briefly reviewed together with the promise of prevention through vaccination.
Topics: Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Epidermodysplasia Verruciformis; Epstein-Barr Virus Infections; Female; Hepacivirus; Hepatitis B virus; Herpesvirus 4, Human; Humans; Leiomyosarcoma; Liver Neoplasms; Lymphoma; Male; Nasopharyngeal Neoplasms; Neoplasms; Oncogenic Viruses; Papillomaviridae; Papillomavirus Infections; Skin Neoplasms; Stomach Neoplasms; Tumor Virus Infections; Uterine Cervical Neoplasms; Viral Vaccines; Vulvar Neoplasms
PubMed: 27723397
DOI: 10.12968/hmed.2016.77.10.565 -
International Journal of Molecular... Nov 2022In the multi-factorial etiology of organ-site cancers by suspect human chemical carcinogens, oncogenic virus, activation of RAS, Myc and HER-2 oncogenes, inactivation of...
In the multi-factorial etiology of organ-site cancers by suspect human chemical carcinogens, oncogenic virus, activation of RAS, Myc and HER-2 oncogenes, inactivation of TP53, RB and APC tumor suppressor genes represent early-occurring genetic events [...].
Topics: Humans; Antineoplastic Agents; Oncogenes; Oncogenic Viruses; Carcinogens; Neoplasms
PubMed: 36430932
DOI: 10.3390/ijms232214457 -
Viruses Jul 2021Insulin-like growth factor-1 (IGF-1) and the IGF-1 receptor (IGF-1R) belong to the insulin-like growth factor family, and IGF-1 activates intracellular signaling... (Review)
Review
Insulin-like growth factor-1 (IGF-1) and the IGF-1 receptor (IGF-1R) belong to the insulin-like growth factor family, and IGF-1 activates intracellular signaling pathways by binding specifically to IGF-1R. The interaction between IGF-1 and IGF-1R transmits a signal through a number of intracellular substrates, including the insulin receptor substrate (IRS) and the Src homology collagen (Shc) proteins, which activate two major intracellular signaling pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways, specifically the extracellular signal-regulated kinase (ERK) pathways. The PI3K/AKT kinase pathway regulates a variety of cellular processes, including cell proliferation and apoptosis. IGF1/IGF-1R signaling also promotes cell differentiation and proliferation via the Ras/MAPK pathway. Moreover, upon IGF-1R activation of the IRS and Shc adaptor proteins, Shc stimulates Raf through the GTPase Ras to activate the MAPKs ERK1 and ERK2, phosphorylate and several other proteins, and to stimulate cell proliferation. The IGF-1 signaling pathway is required for certain viral effects in oncogenic progression and may be induced as an effect of viral infection. The mechanisms of IGF signaling in animal viral infections need to be clarified, mainly because they are involved in multifactorial signaling pathways. The aim of this review is to summarize the current data obtained from virological studies and to increase our understanding of the complex role of the IGF-1 signaling axis in animal virus infections.
Topics: Animals; Humans; Insulin-Like Growth Factor I; Mice; Oncogenic Viruses; Phosphorylation; Receptor, IGF Type 1; Signal Transduction; Virus Diseases
PubMed: 34452353
DOI: 10.3390/v13081488 -
Postepy Biochemii Dec 2020Oncogenic viruses (oncoviruses) are implicated in approximately 12% of all human cancers. Currently, the viruses known to cause human cancer are: Hepatitis B and C...
Oncogenic viruses (oncoviruses) are implicated in approximately 12% of all human cancers. Currently, the viruses known to cause human cancer are: Hepatitis B and C viruses (HBV and HCV), Human Papillomaviruses (HPV), Merkel Cell Polyomavirus (MCV), Human Herpesvirus-8 (HHV-8), Epstein-Barr Virus (EBV) and Human T-cell lymphotropic virus-1 (HTLV-1). However, oncoviruses are not complete carcinogens, need additional factors andisplay different roles in transformation. Oncoviruses can directly disrupt important regulatory cell genes by inserting virus genom into the DNA of the host cell. They also contain their own genes that damage the regulation of the cell. Some viruses have v-onc that cause disregulation of cellular processes and can lead to cancerous growth.
Topics: Hepacivirus; Humans; Neoplasms; Oncogenic Viruses; Retroviridae
PubMed: 33470075
DOI: 10.18388/pb.2020_360 -
Advances in Experimental Medicine and... 2017Kaposi's sarcoma-associated herpesvirus (KSHV), also known as Human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and a human... (Review)
Review
Kaposi's sarcoma-associated herpesvirus (KSHV), also known as Human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and a human oncogenic virus. Since its discovery in AIDS-associated KS tissues by Drs. Yuan Chang and Patrick Moore, much progress has been made in the past two decades. There are four types of KS including classic KS, endemic KS, immunosuppressive therapy-related KS, and AIDS-associated KS. In addition to KS, KSHV is also involved in the development of primary effusion lymphoma (PEL) and certain types of multicentric Castleman's disease. KSHV manipulates numerous viral proteins to promote the progression of angiogenesis and tumorigenesis. In this chapter, we review the epidemiology and molecular biology of KSHV and the mechanisms underlying KSHV-induced diseases.
Topics: Acquired Immunodeficiency Syndrome; Castleman Disease; Herpesvirus 8, Human; Humans; Oncogenic Viruses; Sarcoma, Kaposi
PubMed: 29052134
DOI: 10.1007/978-981-10-5765-6_7 -
Viruses Jun 2022A signature trait of neurotropic α-herpesviruses (α-HV) is their ability to establish stable non-productive infections of peripheral neurons termed latency. This... (Review)
Review
A signature trait of neurotropic α-herpesviruses (α-HV) is their ability to establish stable non-productive infections of peripheral neurons termed latency. This specialized gene expression program is the foundation of an evolutionarily successful strategy to ensure lifelong persistence in the host. Various physiological stresses can induce reactivation in a subset of latently-infected neurons allowing a new cycle of viral productive cycle gene expression and synthesis of infectious virus. Recurring reactivation events ensure transmission of the virus to new hosts and contributes to pathogenesis. Efforts to define the molecular basis of α-HV latency and reactivation have been notoriously difficult because the neurons harboring latent virus in humans and in experimentally infected live-animal models, are rare and largely inaccessible to study. Increasingly, researchers are turning to cultured neuron infection models as simpler experimental platforms from which to explore latency and reactivation at the molecular level. In this review, I reflect on the strengths and weaknesses of existing neuronal models and briefly summarize the important mechanistic insights these models have provided. I also discuss areas where prioritization will help to ensure continued progress and integration.
Topics: Animals; Herpesviridae; Herpesvirus 1, Human; Neurons; Oncogenic Viruses; Virus Activation; Virus Latency
PubMed: 35746680
DOI: 10.3390/v14061209 -
Viruses Dec 2021During initial infection, human papillomaviruses (HPV) take an unusual trafficking pathway through their host cell. It begins with a long period on the cell surface,... (Review)
Review
During initial infection, human papillomaviruses (HPV) take an unusual trafficking pathway through their host cell. It begins with a long period on the cell surface, during which the capsid is primed and a virus entry platform is formed. A specific type of clathrin-independent endocytosis and subsequent retrograde trafficking to the trans-Golgi network follow this. Cellular reorganization processes, which take place during mitosis, enable further virus transport and the establishment of infection while evading intrinsic cellular immune defenses. First, the fragmentation of the Golgi allows the release of membrane-encased virions, which are partially protected from cytoplasmic restriction factors. Second, the nuclear envelope breakdown opens the gate for these virus-vesicles to the cell nucleus. Third, the dis- and re-assembly of the PML nuclear bodies leads to the formation of modified virus-associated PML subnuclear structures, enabling viral transcription and replication. While remnants of the major capsid protein L1 and the viral DNA remain in a transport vesicle, the viral capsid protein L2 plays a crucial role during virus entry, as it adopts a membrane-spanning conformation for interaction with various cellular proteins to establish a successful infection. In this review, we follow the oncogenic HPV type 16 during its long journey into the nucleus, and contrast pro- and antiviral processes.
Topics: Animals; Capsid Proteins; Endocytosis; Epithelial Cells; Human papillomavirus 16; Humans; Papillomavirus Infections; Virus Internalization; trans-Golgi Network
PubMed: 34960729
DOI: 10.3390/v13122460 -
Current Opinion in Virology Oct 2015Human γ-herpesviruses contain Epstein Barr virus (EBV), the first human tumor virus that was identified in man, and Kaposi Sarcoma associated herpesvirus (KSHV), one of... (Review)
Review
Human γ-herpesviruses contain Epstein Barr virus (EBV), the first human tumor virus that was identified in man, and Kaposi Sarcoma associated herpesvirus (KSHV), one of the most recently identified human oncogenic pathogens. Both of these have co-evolved with humans to cause tumors only in a minority of infected individuals, despite their exquisite ability to establish persistent infections. In this review we will summarize the fine-tuned balance between immune responses, immune escape and cellular transformation by these viruses, which results in life-long persistent, but asymptomatic infection with immune control in most virus carriers. A detailed understanding of this balance is required to immunotherapeutically reinstall it in patients that suffer from EBV and KSHV associated malignancies.
Topics: Carcinogenesis; Herpesvirus 4, Human; Herpesvirus 8, Human; Host-Pathogen Interactions; Humans; Immune Evasion; Oncogenic Viruses
PubMed: 26372881
DOI: 10.1016/j.coviro.2015.08.014