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Annals of Gastroenterology 2022Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and is attributable mainly to viral hepatitis, alcohol and nonalcoholic fatty liver disease.
BACKGROUND
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and is attributable mainly to viral hepatitis, alcohol and nonalcoholic fatty liver disease.
METHODS
Three hundred Greek patients diagnosed with HCC between 2000 and 2019 were retrospectively evaluated for patient and HCC characteristics. Patients were classified as before 2011 (A) or after 2011 (B) and HCC risk factors were compared with historic Greek cohorts.
RESULTS
The median age was 64 years and 86% were male; 45% had chronic hepatitis B virus (HBV) infection, 26% chronic hepatitis C virus (HCV) infection, and 30% non-viral liver diseases (nvLD). No change was observed among liver diseases between periods A and B. However, there was a trend towards a decrease in virally and an increase in non-virally induced HCC (P=0.075). Patients in period B (vs. A) were more likely to be diagnosed with fewer (<3, P=0.006) and smaller (<3 cm, P=0.005) nodules. Compared with 1558 Greek HCC patients from 1974-2000, there was a decrease in HBV and an increase in HCV and nvLD-related HCCs (P<0.001).
CONCLUSIONS
In Greece, after 2000, there was a decrease in the proportion of HBV and an increase in the proportion of HCV and nvLD-related HCC, while over the last 2 decades there has been a trend towards a decrease in virally and an increase in non-virally induced HCC. Since 2011, HCC is being diagnosed at an earlier stage, possibly reflecting improved surveillance strategies.
PubMed: 34987294
DOI: 10.20524/aog.2021.0680 -
Cold Spring Harbor Perspectives in... Jun 2021Early studies of transmissible tumors in chickens provided evidence that viruses such as avian leukosis virus (ALV) and Rous sarcoma virus (RSV) can cause cancer in... (Review)
Review
Early studies of transmissible tumors in chickens provided evidence that viruses such as avian leukosis virus (ALV) and Rous sarcoma virus (RSV) can cause cancer in these animals. Doubts about the relevance to human tumors and failures to replicate some early work meant the field of tumor virology followed a bumpy course. Nevertheless, viruses that can cause cancers in rodents and humans were ultimately identified, and several Nobel prizes were awarded for work in this area. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the early history of tumor virus research, from some of the early false starts and debates, to discovery of reverse transcriptase, and identification of human papilloma virus (HPV) as the major cause of cervical cancer.
Topics: Animals; History, 20th Century; Humans; Neoplasms; Oncogenic Viruses; Proviruses; Virology
PubMed: 34074674
DOI: 10.1101/cshperspect.a035774 -
Virus Research Apr 2021Flaviviruses are the fastest spreading arthropod-borne viruses that cause severe symptoms such as hepatitis, hemorrhagic fever, encephalitis, and congenital deformities.... (Review)
Review
Flaviviruses are the fastest spreading arthropod-borne viruses that cause severe symptoms such as hepatitis, hemorrhagic fever, encephalitis, and congenital deformities. Nearly 40 % of the entire human population is at risk of flavivirus epidemics. Yet, effective vaccination is restricted only to a few flaviviruses such as yellow fever and Japanese encephalitis viruses, and most recently for select cases of dengue virus infections. Despite the global spread of dengue virus, and emergence of new threats such as Zika virus and a new genotype of Japanese encephalitis virus, insights into flavivirus targets for potentially broad-spectrum vaccination are limited. In this review article, we highlight biochemical and structural differences in flavivirus proteins critical for virus assembly and host interactions. A comparative sequence analysis of pH-responsive properties of viral structural proteins identifies trends in conservation of complementary acidic-basic character between interacting viral structural proteins. This is highly relevant to the understanding of pH-sensitive differences in virus assembly in organelles such as neutral ER and acidic Golgi. Surface residues in viral interfaces identified by structural approaches are shown to demonstrate partial conservation, further reinforcing virus-specificity in assembly and interactions with host proteins. A comparative analysis of epitope conservation in emerging flaviviruses identifies therapeutic antibody candidates that have potential as broad spectrum anti-virals, thus providing a path towards development of vaccines.
Topics: Flavivirus; Flavivirus Infections; Humans; Viral Structural Proteins; Yellow Fever; Zika Virus; Zika Virus Infection
PubMed: 33607183
DOI: 10.1016/j.virusres.2021.198343 -
The Journal of General Virology May 2021Viral latency is an active process during which the host cell environment is optimized for latent carriage and reactivation. This requires control of both viral and host...
Viral latency is an active process during which the host cell environment is optimized for latent carriage and reactivation. This requires control of both viral and host gene promoters and enhancers often at the level of chromatin, and several viruses co-opt the chromatin organiser CTCF to control gene expression during latency. While CTCF has a role in the latencies of alpha- and gamma-herpesviruses, it was not known whether CTCF played a role in the latency of the beta-herpesvirus human cytomegalovirus (HCMV). Here, we show that HCMV latency is associated with increased CTCF expression and CTCF binding to the viral major lytic promoter, the major immediate early promoter (MIEP). This increase in CTCF binding is dependent on the virally encoded G protein coupled receptor, US28, and contributes to suppression of MIEP-driven transcription, a hallmark of latency. Furthermore, we show that latency-associated upregulation of CTCF represses expression of the neutrophil chemoattractants S100A8 and S100A9 which we have previously shown are downregulated during HCMV latency. As with downregulation of the MIEP, CTCF binding to the enhancer region of S100A8/A9 drives their suppression, again in a US28-dependent manner. Taken together, we identify CTCF upregulation as an important mechanism for optimizing latent carriage of HCMV at both the levels of viral and cellular gene expression.
Topics: CCCTC-Binding Factor; Calgranulin A; Calgranulin B; Cytomegalovirus; Cytomegalovirus Infections; Enhancer Elements, Genetic; Gene Expression Regulation; Genes, Immediate-Early; Host-Pathogen Interactions; Humans; Monocytes; Promoter Regions, Genetic; Receptors, Chemokine; Viral Proteins; Virus Latency
PubMed: 34042564
DOI: 10.1099/jgv.0.001609 -
Frontiers in Immunology 2020The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This "cytokine storm" produces an excessive... (Review)
Review
The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This "cytokine storm" produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities. In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1, and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases and conditions often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Cytokines; Humans; Immunologic Factors; Inflammation; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 33072097
DOI: 10.3389/fimmu.2020.558898 -
Nature Feb 2022Public databases contain a planetary collection of nucleic acid sequences, but their systematic exploration has been inhibited by a lack of efficient methods for...
Public databases contain a planetary collection of nucleic acid sequences, but their systematic exploration has been inhibited by a lack of efficient methods for searching this corpus, which (at the time of writing) exceeds 20 petabases and is growing exponentially. Here we developed a cloud computing infrastructure, Serratus, to enable ultra-high-throughput sequence alignment at the petabase scale. We searched 5.7 million biologically diverse samples (10.2 petabases) for the hallmark gene RNA-dependent RNA polymerase and identified well over 10 novel RNA viruses, thereby expanding the number of known species by roughly an order of magnitude. We characterized novel viruses related to coronaviruses, hepatitis delta virus and huge phages, respectively, and analysed their environmental reservoirs. To catalyse the ongoing revolution of viral discovery, we established a free and comprehensive database of these data and tools. Expanding the known sequence diversity of viruses can reveal the evolutionary origins of emerging pathogens and improve pathogen surveillance for the anticipation and mitigation of future pandemics.
Topics: Animals; Archives; Bacteriophages; Biodiversity; Cloud Computing; Coronavirus; Databases, Genetic; Evolution, Molecular; Hepatitis Delta Virus; Humans; Models, Molecular; RNA Viruses; RNA-Dependent RNA Polymerase; Sequence Alignment; Software; Virology; Virome
PubMed: 35082445
DOI: 10.1038/s41586-021-04332-2 -
Genes & Diseases Nov 2023Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV),... (Review)
Review
Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV), Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus (HTLV), and Merkel cell polyomavirus (MCV)) that infect humans have been identified as an oncogene and have been associated with several human malignancies. Recently, growing attention has been attracted to exploring the pathogenesis of virus-related cancers. One of the most mysterious molecules involved in carcinogenesis and progression of virus-related cancers is circular RNAs (circRNA). These emerging non-coding RNAs (ncRNAs), due to the absence of 5' and 3' ends, have high stability than linear RNAs and are found in some species across the eukaryotic organisms. Compelling evidence has revealed that viruses also encode a repertoire of circRNAs, as well as dysregulation of these viral circRNAs play a critical role in the pathogenesis and progression of different types of virus-related cancers. Therefore, understanding the exact role and function of the virally encoded circRNAs with virus-associated cancers will open a new road for increasing our knowledge about the RNA world. Hence, in this review, we will focus on emerging roles of virus-encoded circRNAs in multiple cancers, including cervical cancer, gastric cancer, Merkel cell carcinoma, nasopharyngeal carcinoma, Kaposi cancer, and liver cancer.
PubMed: 37554189
DOI: 10.1016/j.gendis.2022.04.009 -
Biomedicine & Pharmacotherapy =... Mar 2022The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths... (Review)
Review
The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.
Topics: Alkaloids; Antiviral Agents; Benzaldehydes; Benzoquinones; Caffeic Acids; Cinnamates; Depsides; Ellagic Acid; Humans; Phytochemicals; Phytotherapy; Quercetin; SARS-CoV-2; Thymol; Triterpenes; COVID-19 Drug Treatment; Rosmarinic Acid; Ursolic Acid
PubMed: 35066300
DOI: 10.1016/j.biopha.2022.112658 -
Nutrients Mar 2020Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic... (Review)
Review
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients.
Topics: Animals; Humans; Polymorphism, Genetic; Receptors, Calcitriol; Virus Diseases; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein
PubMed: 32235600
DOI: 10.3390/nu12040962 -
International Journal of Molecular... Jan 2022Cell death by apoptosis is a major cellular response in the control of tissue homeostasis and as a defense mechanism in the case of cellular aggression such as an... (Review)
Review
Cell death by apoptosis is a major cellular response in the control of tissue homeostasis and as a defense mechanism in the case of cellular aggression such as an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the spread of a virus. Although it may contribute to the deleterious effects in infectious pathology, apoptosis remains a key mechanism for viral clearance and the resolution of infection. The control mechanisms of cell death processes by viruses have been extensively studied. Apoptosis can be triggered by different viral determinants through different pathways as a result of virally induced cell stresses and innate immune responses. Zika virus (ZIKV) induces Zika disease in humans, which has caused severe neurological forms, birth defects, and microcephaly in newborns during the last epidemics. ZIKV also surprised by revealing an ability to persist in the genital tract and in semen, thus being sexually transmitted. Mechanisms of diverting antiviral responses such as the interferon response, the role of cytopathic effects and apoptosis in the etiology of the disease have been widely studied and debated. In this review, we examined the interplay between ZIKV infection of different cell types and apoptosis and how the virus deals with this cellular response. We illustrate a duality in the effects of ZIKV-controlled apoptosis, depending on whether it occurs too early or too late, respectively, in neuropathogenesis, or in long-term viral persistence. We further discuss a prospective role for apoptosis in ZIKV-related therapies, and the use of ZIKV as an oncolytic agent.
Topics: Animals; Antiviral Agents; Apoptosis; Cell Death; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferons; Microcephaly; Virus Physiological Phenomena; Virus Replication; Zika Virus; Zika Virus Infection
PubMed: 35163212
DOI: 10.3390/ijms23031287