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Trends in Molecular Medicine Mar 2023Endothelial-to-mesenchymal transition has been described in tumors as a source of mesenchymal stroma, while the reverse process has been proposed in tumor vasculogenesis... (Review)
Review
Endothelial-to-mesenchymal transition has been described in tumors as a source of mesenchymal stroma, while the reverse process has been proposed in tumor vasculogenesis and angiogenesis. A human oncogenic virus, Kaposi's sarcoma herpes virus (KSHV), can regulate both processes in order to transit through this transition 'boulevard' when infecting KS oncogenic progenitor cells. Endothelial or mesenchymal circulating progenitor cells can serve as KS oncogenic progenitors recruited by inflammatory cytokines because KSHV can reprogram one into the other through endothelial-to-mesenchymal and mesenchymal-to-endothelial transitions. Through these novel insights, the identity of the potential oncogenic progenitor of KS is revealed while gaining knowledge of the biology of the mesenchymal-endothelial differentiation axis and pointing to this axis as a therapeutic target in KS.
Topics: Humans; Sarcoma, Kaposi; Herpesvirus 8, Human; Cell Differentiation
PubMed: 36635149
DOI: 10.1016/j.molmed.2022.12.003 -
Viruses May 2021Human oncogenic viruses account for at least 12% of total cancer cases worldwide. Epstein-Barr virus (EBV) is the first identified human oncogenic virus and it alone... (Review)
Review
Human oncogenic viruses account for at least 12% of total cancer cases worldwide. Epstein-Barr virus (EBV) is the first identified human oncogenic virus and it alone causes ~200,000 cancer cases and ~1.8% of total cancer-related death annually. Over the past 40 years, increasing lines of evidence have supported a causal link between EBV infection and a subgroup of lung cancers (LCs). In this article, we review the current understanding of the EBV-LC association and the etiological role of EBV in lung carcinogenesis. We also discuss the clinical impact of the knowledge gained from previous research, challenges, and future directions in this field. Given the high clinical relevance of EBV-LC association, there is an urgent need for further investigation on this topic.
Topics: Animals; Cell Transformation, Viral; Disease Models, Animal; Disease Susceptibility; Epstein-Barr Virus Infections; Gene Expression Regulation, Viral; Herpesvirus 4, Human; Humans; Lung Neoplasms; Virus Latency
PubMed: 34064727
DOI: 10.3390/v13050877 -
Current Oncology Reports Jul 2022This study assesses the current state of knowledge of head and neck squamous cell carcinomas (HNSCC), which are malignancies arising from the orifices and adjacent... (Review)
Review
PURPOSE OF REVIEW
This study assesses the current state of knowledge of head and neck squamous cell carcinomas (HNSCC), which are malignancies arising from the orifices and adjacent mucosae of the aerodigestive tracts. These contiguous anatomical areas are unique in that 2 important human oncoviruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are causally associated with nasopharyngeal and oropharyngeal cancers, respectively. Mortality rates have remained high over the last 4 decades, and insufficient attention paid to the unique viral and clinical oncology of the different subgroups of HNSCC.
RECENT FINDINGS
We have compared and contrasted the 2 double-stranded DNA viruses and the relevant molecular oncogenesis of their respective cancers against other head and neck cancers. Tobacco and alcohol ingestion are also reviewed, as regard the genetic progression/mutation accumulation model of carcinogenesis. The importance of stringent stratification when searching for cancer mutations and biomarkers is discussed. Evidence is presented for a dysplastic/pre-invasive cancerous phase for HPV+ oropharyngeal cancers, and analogous with other HPV+ cancers. This raises the possibility of strategies for cancer screening as early diagnosis will undoubtedly save lives. Staging and prognostication have changed to take into account the distinct biological and prognostic pathways for viral+ and viral- cancers. Diagnosis of pre-cancers and early stage cancers will reduce mortality rates. Multi-modal treatment options for HNSCC are reviewed, especially recent developments with immunotherapies and precision medicine strategies. Knowledge integration of the viral and molecular oncogenic pathways with sound planning, hypothesis generation, and clinical trials will continue to provide therapeutic options in the future.
Topics: Carcinoma, Squamous Cell; Epstein-Barr Virus Infections; Head and Neck Neoplasms; Herpesvirus 4, Human; Humans; Medical Oncology; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 35347592
DOI: 10.1007/s11912-022-01263-7 -
Virology Journal Nov 2021Toll-like receptors (TLRs) control anti-viral responses both directly in infected cells and in responding cells of the immune systems. Therefore, they are crucial for... (Review)
Review
Toll-like receptors (TLRs) control anti-viral responses both directly in infected cells and in responding cells of the immune systems. Therefore, they are crucial for responses against the oncogenic γ-herpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and the related murine virus MHV68, which directly infect immune system cells. However, since these viruses also cause lifelong persistent infections, TLRs may also be involved in modulation of inflammation during latent infection and contribute to virus-driven tumorigenesis. This review summarizes work on both of these aspects of TLR/γ-herpesvirus interactions, as well as results showing that TLR activity can drive these viruses' re-entry into the replicative lytic cycle.
Topics: Animals; Antiviral Agents; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; Mice; Toll-Like Receptors; Virus Latency; Virus Replication
PubMed: 34749760
DOI: 10.1186/s12985-021-01678-x -
Viruses Dec 2019Viral lymphomagenesis induced by infection with oncogenic viruses, such as Kaposi's sarcoma associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human T-cell... (Review)
Review
Viral lymphomagenesis induced by infection with oncogenic viruses, such as Kaposi's sarcoma associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human T-cell leukemia virus (HTLV-1), represents a group of aggressive malignancies with a diverse range of pathological features. Combined chemotherapy remains the standard of care for these virus-associated lymphomas; however, frequent chemoresistance is a barrier to achieving successful long-term disease-free survival. There is increasing evidence that indicates virus-associated lymphomas display more resistance to cytotoxic chemotherapeutic agents than that observed in solid tumors. Although the tumor microenvironment and genetic changes, such as key oncogene mutations, are closely related to chemoresistance, some studies demonstrate that the components of oncogenic viruses themselves play pivotal roles in the multidrug chemoresistance of lymphoma cells. In this review, we summarize recent advances in the understanding of the mechanisms through which oncogenic viruses mediate lymphoma cell chemoresistance, with a particular focus on KSHV and EBV, two major oncogenic viruses. We also discuss the current challenges to overcome these obstacles in the treatment of virus-associated lymphomas.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Drug Resistance, Neoplasm; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoma; Oncogenic Viruses; Tumor Virus Infections
PubMed: 31888174
DOI: 10.3390/v11121161 -
Viruses Nov 2021Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant... (Review)
Review
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.
Topics: Alphapapillomavirus; Biomarkers, Tumor; Carcinogenesis; Epigenesis, Genetic; Humans; Immune Evasion; Neoplasms; Oncogene Proteins, Viral; Papillomavirus Infections
PubMed: 34835040
DOI: 10.3390/v13112234 -
Current Opinion in Virology Dec 2019Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and... (Review)
Review
Oncogenic viruses, like all viruses, relies on host metabolism to provide the metabolites and energy needed for virus replication. Many DNA tumor viruses and retroviruses will reprogram metabolism during infection. Additionally, some viral oncogenes may alter metabolism independent of virus replication. Virus infection and cancer development share many similarities regarding metabolic reprogramming as both processes demand increased metabolic activity to produce biomass: cell proliferation in the case of cancer and virion production in the case of infection. This review discusses the parallels in metabolic reprogramming between human oncogenic viruses and oncogenesis.
Topics: Biomass; Carcinogenesis; Cell Proliferation; Cellular Reprogramming; Hepacivirus; Hepatitis B virus; Herpesviridae; Humans; Merkel cell polyomavirus; Metabolic Networks and Pathways; Neoplasms; Oncogenic Viruses; Papillomaviridae; Retroviridae; Virion; Virus Replication
PubMed: 31766001
DOI: 10.1016/j.coviro.2019.11.002 -
The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy.Cancers Feb 2022Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors... (Review)
Review
Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors and a few atypical receptors also with decoy activity. They are well-described targets of oncogenic pathways and key players in cancer development, invasiveness, and metastasis acting both at the level of cancer cells and cells of the tumor microenvironment. Hence, they can regulate cancer cell proliferation and survival and promote immune or endothelial cell migration into the tumor microenvironment. Additionally, oncogenic viruses display the potential of jeopardizing the chemokine system by encoding mimics of chemokines and receptors as well as several products such as oncogenic proteins or microRNAs that deregulate their human host transcriptome. Conversely, the chemokine system participates in the host responses that control the virus life cycle, knowing that most oncoviruses establish asymptomatic latent infections. Therefore, the deregulated expression and function of chemokines and receptors as a consequence of acquired or inherited mutations could bias oncovirus infection toward pro-oncogenic pathways. We here review these different processes and discuss the anticancer therapeutic potential of targeting chemokine availability or receptor activation, from signaling to decoy-associated functions, in combination with immunotherapies.
PubMed: 35159113
DOI: 10.3390/cancers14030848 -
Emerging Microbes & Infections Dec 2023Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes...
Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and EBV-induced lymphoma. Neutralizing epitopes targeted by antibodies 1A7 and 6G7 are distinct and novel. Antibody 6G7 blocks gp42 binding to B cell surface and both 1A7 and 6G7 inhibit membrane fusion with B cells. Furthermore, 1A7- and 6G7-like antibodies in immunized sera are major contributors to B cell neutralization. This study demonstrates that anti-gp42 neutralizing antibodies are effective in inhibiting EBV infection and sheds light on the design of gp42-based vaccines and therapeutics.
Topics: Rabbits; Humans; Animals; Mice; Herpesvirus 4, Human; Antibodies, Neutralizing; Epstein-Barr Virus Infections; Membrane Glycoproteins; Viral Proteins; Epitopes
PubMed: 37542379
DOI: 10.1080/22221751.2023.2245920 -
Viruses Mar 2021I was fortunate to be associated with the lab of Stephen Oroszlan at the US National Cancer Institute from ~1982 until his conversion to Emeritus status in 1995. His lab...
I was fortunate to be associated with the lab of Stephen Oroszlan at the US National Cancer Institute from ~1982 until his conversion to Emeritus status in 1995. His lab made groundbreaking discoveries on retroviral proteins during that time, including many features that could not have been inferred or anticipated from straightforward sequence information. Building on the Oroszlan lab results, my colleagues and I demonstrated that the zinc fingers in nucleocapsid proteins play a crucial role in genomic RNA encapsidation; that the N-terminal myristylation of the Gag proteins of many retroviruses is important for their association with the plasma membrane before particle assembly is completed; and that gammaretroviruses initially synthesize their Env protein as an inactive precursor and then truncate the cytoplasmic tail of the transmembrane protein, activating Env fusogenicity, during virus maturation. We also elucidated several aspects of the mechanism of translational suppression in gene expression in gammaretroviruses; amazingly, this is a fundamentally different mechanism of suppression from that in most other retroviral genera.
Topics: Cell Membrane; History, 21st Century; Retroviridae; Viral Proteins
PubMed: 33809689
DOI: 10.3390/v13030491