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1.
Int J Oncol ; 60(4)2022 04.
Article in English | MEDLINE | ID: covidwho-1726131

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is highly infectious and pathogenic. Among patients with severe SARS­CoV­2­caused by corona virus disease 2019 (COVID­19), those complicated with malignant tumor are vulnerable to COVID­19 due to compromised immune function caused by tumor depletion, malnutrition and anti­tumor treatment. Cancer is closely related to the risk of severe illness and mortality in patients with COVID­19. SARS­CoV­2 could promote tumor progression and stimulate metabolism switching in tumor cells to initiate tumor metabolic modes with higher productivity efficiency, such as glycolysis, for facilitating the massive replication of SARS­CoV­2. However, it has been shown that infection with SARS­CoV­2 leads to a delay in tumor progression of patients with natural killer cell (NK cell) lymphoma and Hodgkin's lymphoma, while SARS­CoV­2 elicited anti­tumor immune response may exert a potential oncolytic role in lymphoma patients. The present review briefly summarized potential carcinogenicity and oncolytic characteristics of SARS­CoV­2 as well as strategies to protect patients with cancer during the COVID­19 pandemic.


Subject(s)
COVID-19/complications , Neoplasms/etiology , SARS-CoV-2 , Androgen Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 Vaccines/immunology , Humans , Neoplasms/prevention & control , Neoplasms/therapy , Probiotics/administration & dosage , Tumor Virus Infections/complications
2.
Pediatrics ; 148(5)2021 11.
Article in English | MEDLINE | ID: covidwho-1707239

ABSTRACT

OBJECTIVES: We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. METHODS: This cohort study included 139 100 children born at ≥35 weeks' gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. RESULTS: Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. CONCLUSIONS: We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.


Subject(s)
Neoplasms/etiology , Phototherapy/adverse effects , Bilirubin/blood , California/epidemiology , Child , Child, Preschool , Epidemiologic Methods , Female , Humans , Incidence , Male , Negative Results , Neoplasms/epidemiology , Time Factors
3.
Int J Biol Sci ; 17(14): 3795-3817, 2021.
Article in English | MEDLINE | ID: covidwho-1459010

ABSTRACT

Background: SARS-CoV-2, the cause of the worldwide COVID-19 pandemic, utilizes the mechanism of binding to ACE2 (a crucial component of the renin-angiotensin system [RAS]), subsequently mediating a secondary imbalance of the RAS family and leading to severe injury to the host. However, very few studies have been conducted to reveal the mechanism behind the effect of SARS-CoV-2 on tumors. Methods: Demographic data extracted from 33 cancer types and over 10,000 samples were employed to determine the comprehensive landscape of the RAS. Expression distribution, pretranscriptional and posttranscriptional regulation and posttranslational modifications (PTMs) as well as genomic alterations, DNA methylation and m6A modification were analyzed in both tissue and cell lines. The clinical phenotype, prognostic value and significance of the RAS during immune infiltration were identified. Results: Low expression of AGTR1 was common in tumors compared to normal tissues, while very low expression of AGTR2 and MAS1 was detected in both tissues and cell lines. Differential expression patterns of ACE in ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC) were correlated with ubiquitin modification involving E3 ligases. Genomic alterations of the RAS family were infrequent across TCGA pan-cancer program, and ACE had the highest alteration frequency compared with other members. Low expression of AGTR1 may result from hypermethylation in the promoter. Downregulation of RAS family was linked to higher clinical stage and worse survival (as measured by disease-specific survival [DSS], overall survival [OS] or progression-free interval [PFI]), especially for ACE2 and AGTR1 in KIRC. ACE-AGTR1, a classical axis of the RAS family related to immune infiltration, was positively correlated with M2-type macrophages, cancer-associated fibroblasts (CAFs) and immune checkpoint genes in most cancers. Conclusion: ACE, ACE2, AGT and AGTR1 were differentially expressed in 33 types of cancers. PTM of RAS family was found to rely on ubiquitination. ACE2 and AGTR1 might serve as independent prognostic factors for LGG and KIRC. SARS-CoV-2 might modify the tumor microenvironment by regulating the RAS family, thus affecting the biological processes of cancer.


Subject(s)
Neoplasms/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , COVID-19/complications , COVID-19/metabolism , DNA Methylation , Gene Expression Regulation, Neoplastic , Humans , Immunotherapy , Neoplasms/etiology , Neoplasms/mortality , Neoplasms/therapy , Protein Processing, Post-Translational
4.
Anticancer Res ; 41(6): 2745-2757, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1404214

ABSTRACT

BACKGROUND/AIM: Seventy-six years after Auschwitz Liberation, the Holocaust keeps on persecuting its surviving victims. As witnessed by the psychiatric and medical literature in the last decades, in fact, the Holocaust survivors (HS) appear to suffer from several Shoah-related late-onset diseases impacting their survival, such as internal illnesses and post-traumatic stress disorder (PTSD). Cancer represents a further severe pathology which seems to be connected with the Holocaust experience. Our aim was to review the existing knowledge of Holocaust-related cancer in HS in order to assess its real incidence and clinicoprognostic significance. MATERIALS AND METHODS: We systematically reviewed the literature dealing with Israeli Jewish and non-Jewish non-Israeli HS developing cancer. We also reviewed and analyzed the cancer data of noted Jewish HS not resident or having resided in Israel available as public information. RESULTS: We found 16 and 15 studies on Israeli Jews and non-Jewish non-Israeli survivors, respectively. A statistically significant association between the Holocaust and development of late-onset cancer in HS was seen in most studies with cancer adversely impacting the survival. We also selected 330 noted Jewish non-Israeli HS: genocide-related late-onset cancer resulted to be a significant and independent risk factor of poor prognosis (p<0.0001) imparting shorter survival in affected versus non-cancer subjects (57 versus 64 years, respectively, p=0.0001). CONCLUSION: Although 76 years have passed, our review shows how the Holocaust keeps on burdening its survivors. Moreover, we offered the first analysis of Jewish HS not resident or having resided in Israel in terms of genocide-related late-onset diseases focusing on cancer. Further studies on Jewish non-Israeli HS are needed in order to corroborate our findings on late-onset cancer occurring in this targeted population.


Subject(s)
Holocaust/psychology , Jews , Neoplasms/etiology , Survivors/psychology , Age of Onset , Aged , Humans , Israel , Neoplasms/epidemiology , Neoplasms/pathology , Risk Factors , Survival Analysis
5.
Front Immunol ; 12: 712722, 2021.
Article in English | MEDLINE | ID: covidwho-1394761

ABSTRACT

The activating immune receptor natural killer group member D (NKG2D) and its cognate ligands represent a fundamental surveillance system of cellular distress, damage or transformation. Signaling through the NKG2D receptor-ligand axis is critical for early detection of viral infection or oncogenic transformation and the presence of functional NKG2D ligands (NKG2D-L) is associated with tumor rejection and viral clearance. Many viruses and tumors have developed mechanisms to evade NKG2D recognition via transcriptional, post-transcriptional or post-translational interference with NKG2D-L, supporting the concept that circumventing immune evasion of the NKG2D receptor-ligand axis may be an attractive therapeutic avenue for antiviral therapy or cancer immunotherapy. To date, the complexity of the NKG2D receptor-ligand axis and the lack of specificity of current NKG2D-targeting therapies has not allowed for the precise manipulation required to optimally harness NKG2D-mediated immunity. However, with the discovery of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins, novel opportunities have arisen in the realm of locus-specific gene editing and regulation. Here, we give a brief overview of the NKG2D receptor-ligand axis in humans and discuss the levels at which NKG2D-L are regulated and dysregulated during viral infection and oncogenesis. Moreover, we explore the potential for CRISPR-based technologies to provide novel therapeutic avenues to improve and maximize NKG2D-mediated immunity.


Subject(s)
CRISPR-Cas Systems , Gene Editing , NK Cell Lectin-Like Receptor Subfamily K/genetics , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Disease Resistance , Disease Susceptibility , Epigenesis, Genetic , Gene Editing/methods , Genetic Therapy , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity/genetics , Ligands , Neoplasms/etiology , Protein Binding , Virus Diseases/etiology
6.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188622, 2021 12.
Article in English | MEDLINE | ID: covidwho-1377662

ABSTRACT

Since the identification of the first human oncogenic virus in 1964, viruses have been studied for their potential role in aiding the development of cancer. Through the modulation of cellular pathways associated with proliferation, immortalization, and inflammation, viral proteins can mimic the effect of driver mutations and contribute to transformation. Aside from the modulation of signaling pathways, the insertion of viral DNA into the host genome and the deregulation of cellular miRNAs represent two additional mechanisms implicated in viral oncogenesis. In this review, we will discuss the role of twelve different viruses on cancer development and how these viruses utilize the abovementioned mechanisms to influence oncogenesis. The identification of specific mechanisms behind viral transformation of human cells could further elucidate the process behind cancer development.


Subject(s)
Cell Transformation, Neoplastic/genetics , Neoplasms/etiology , Neoplasms/virology , Virus Diseases/complications , Humans , Virus Diseases/pathology
7.
Int J Mol Sci ; 22(7)2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1299439

ABSTRACT

The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS. It is implicated in a variety of physiological and pathological states and an attractive pharmacological target yet to reach its full potential. This review will focus on the involvement of ECS in glucose and lipid metabolism, food intake regulation, immune homeostasis, respiratory health, inflammation, cancer and other physiological and pathological states will be substantiated using freely available data from open-access databases, experimental data and literature review. Future directions should envision capturing its diversity and exploiting pharmacological options beyond the classical ECS suspects (exogenous cannabinoids and cannabinoid receptor monomers) as signaling through cannabinoid receptor heteromers offers new possibilities for different biochemical outcomes in the cell.


Subject(s)
Endocannabinoids/metabolism , Metabolic Networks and Pathways , Receptors, Cannabinoid/metabolism , Animals , Appetite Regulation , Carbohydrate Metabolism , Endocannabinoids/immunology , Humans , Lipid Metabolism , Neoplasms/etiology , Neoplasms/metabolism , Respiration Disorders/immunology , Respiration Disorders/metabolism
9.
Int J Mol Sci ; 22(12)2021 Jun 18.
Article in English | MEDLINE | ID: covidwho-1282514

ABSTRACT

Nanotechnology is an important application in modern cancer therapy. In comparison with conventional drug formulations, nanoparticles ensure better penetration into the tumor mass by exploiting the enhanced permeability and retention effect, longer blood circulation times by a reduced renal excretion and a decrease in side effects and drug accumulation in healthy tissues. The most significant classes of nanoparticles (i.e., liposomes, inorganic and organic nanoparticles) are here discussed with a particular focus on their use as delivery systems for small molecule tyrosine kinase inhibitors (TKIs). A number of these new compounds (e.g., Imatinib, Dasatinib, Ponatinib) have been approved as first-line therapy in different cancer types but their clinical use is limited by poor solubility and oral bioavailability. Consequently, new nanoparticle systems are necessary to ameliorate formulations and reduce toxicity. In this review, some of the most important TKIs are reported, focusing on ongoing clinical studies, and the recent drug delivery systems for these molecules are investigated.


Subject(s)
Antineoplastic Agents/pharmacology , Nanotechnology , Protein Kinase Inhibitors/pharmacology , Theranostic Nanomedicine , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Drug Compounding , Drug Evaluation, Preclinical , Humans , Nanoparticles/chemistry , Neoplasms/diagnosis , Neoplasms/drug therapy , Neoplasms/etiology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Structure-Activity Relationship , Treatment Outcome
10.
Int J Environ Res Public Health ; 18(11)2021 06 05.
Article in English | MEDLINE | ID: covidwho-1264441

ABSTRACT

Besides our current health concerns due to COVID-19, cancer is a longer-lasting and even more dramatic pandemic that affects almost a third of the human population worldwide. Most of the emphasis on its causes has been posed on genetic predisposition, chance, and wrong lifestyles (mainly, obesity and smoking). Moreover, our medical weapons against cancers have not improved too much during the last century, although research is in progress. Once diagnosed with a malignant tumour, we still rely on surgery, radiotherapy, and chemotherapy. The main problem is that we have focused on fighting a difficult battle instead of preventing it by controlling its triggers. Quite the opposite, our knowledge of the links between environmental pollution and cancer has surged from the 1980s. Carcinogens in water, air, and soil have continued to accumulate disproportionally and grow in number and dose, bringing us to today's carnage. Here, a synthesis and critical review of the state of the knowledge of the links between cancer and environmental pollution in the three environmental compartments is provided, research gaps are briefly discussed, and some future directions are indicated. New evidence suggests that it is relevant to take into account not only the dose but also the time when we are exposed to carcinogens. The review ends by stressing that more dedication should be put into studying the environmental causes of cancers to prevent and avoid curing them, that the precautionary approach towards environmental pollutants must be much more reactionary, and that there is an urgent need to leave behind the outdated petrochemical-based industry and goods production.


Subject(s)
Air Pollution , COVID-19 , Environmental Pollutants , Neoplasms , Environmental Pollution , Humans , Neoplasms/epidemiology , Neoplasms/etiology , SARS-CoV-2
11.
Int J Mol Sci ; 22(9)2021 Apr 21.
Article in English | MEDLINE | ID: covidwho-1231490

ABSTRACT

Obesity is globally a serious public health concern and is associated with a high risk of cardiovascular disease (CVD) and various types of cancers. It is important to evaluate various types of obesity, such as visceral and sarcopenic obesity. The evidence on the associated risk of CVD, cancer and sarcopenic obesity, including pathophysiological aspects, occurrence, clinical implications and survival, needs further investigation. Sarcopenic obesity is a relatively new term. It is a clinical condition that primarily affects older adults. There are several endocrine-hormonal, metabolic and lifestyle aspects involved in the occurrence of sarcopenic obesity that affect pathophysiological aspects that, in turn, contribute to CVD and neoplasms. However, there is no available evidence on the role of sarcopenic obesity in the occurrence of CVD and cancer and its pathophysiological interplay. Therefore, this review aims to describe the pathophysiological aspects and the clinical and epidemiological evidence on the role of sarcopenic obesity related to the occurrence and mortality risk of various types of cancer and cardiovascular disease. This literature review highlights the need for further research on sarcopenic obesity to demonstrate the interrelation of these various associations.


Subject(s)
Cardiovascular Diseases/physiopathology , Neoplasms/physiopathology , Obesity/complications , Sarcopenia/complications , Animals , Cardiovascular Diseases/etiology , Humans , Neoplasms/etiology
12.
BMC Infect Dis ; 21(1): 391, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1215099

ABSTRACT

BACKGROUND: Accurately predicting outcomes for cancer patients with COVID-19 has been clinically challenging. Numerous clinical variables have been retrospectively associated with disease severity, but the predictive value of these variables, and how multiple variables interact to increase risk, remains unclear. METHODS: We used machine learning algorithms to predict COVID-19 severity in 348 cancer patients at Memorial Sloan Kettering Cancer Center in New York City. Using only clinical variables collected on or before a patient's COVID-19 positive date (time zero), we sought to classify patients into one of three possible future outcomes: Severe-early (the patient required high levels of oxygen support within 3 days of being tested positive for COVID-19), Severe-late (the patient required high levels of oxygen after 3 days), and Non-severe (the patient never required oxygen support). RESULTS: Our algorithm classified patients into these classes with an area under the receiver operating characteristic curve (AUROC) ranging from 70 to 85%, significantly outperforming prior methods and univariate analyses. Critically, classification accuracy is highest when using a potpourri of clinical variables - including basic patient information, pre-existing diagnoses, laboratory and radiological work, and underlying cancer type - suggesting that COVID-19 in cancer patients comes with numerous, combinatorial risk factors. CONCLUSIONS: Overall, we provide a computational tool that can identify high-risk patients early in their disease progression, which could aid in clinical decision-making and selecting treatment options.


Subject(s)
COVID-19/etiology , Decision Support Systems, Clinical , Machine Learning , Neoplasms/etiology , Risk Factors , Aged , Aged, 80 and over , Algorithms , Area Under Curve , COVID-19/epidemiology , COVID-19/therapy , Comorbidity , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/virology , New York City/epidemiology , Prognosis , ROC Curve , Respiration, Artificial , Retrospective Studies , Severity of Illness Index
14.
Bioessays ; 43(6): e2000331, 2021 06.
Article in English | MEDLINE | ID: covidwho-1206752

ABSTRACT

As the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to surge worldwide, our knowledge of coronavirus disease 2019 (COVID-19) is rapidly expanding. Although most COVID-19 patients recover within weeks of symptom onset, some experience lingering symptoms that last for months ("long COVID-19"). Early reports of COVID-19 sequelae, including cardiovascular, pulmonary, and neurological conditions, have raised concerns about the long-term effects of COVID-19, especially in hard-hit communities. It is becoming increasingly evident that cancer patients are more susceptible to SARS-CoV-2 infection and are at a higher risk of severe COVID-19 than the general population. Nevertheless, whether long COVID-19 increases the risk of cancer in those with no prior malignancies, remains unclear. Given, the disproportionate impact of the disease on the African American community, yet another unanswered question is whether racial disparities are to be expected in COVID-19 sequelae. Herein, we propose that long COVID-19 may predispose recovered patients to cancer development and accelerate cancer progression. This hypothesis is based on growing evidence of the ability of SARS-CoV-2 to modulate oncogenic pathways, promote chronic low-grade inflammation, and cause tissue damage. Comprehensive studies are urgently required to elucidate the effects of long COVID-19 on cancer susceptibility.


Subject(s)
COVID-19/complications , Neoplasms/etiology , African Americans , COVID-19/etiology , COVID-19/immunology , Cytokines/metabolism , Health Status Disparities , Humans , Neoplasms/virology , Race Factors
15.
Front Immunol ; 11: 1554, 2020.
Article in English | MEDLINE | ID: covidwho-1194588

ABSTRACT

The RNase T2 family consists of evolutionarily conserved endonucleases that express in many different species, including animals, plants, protozoans, bacteria, and viruses. The main biological roles of these ribonucleases are cleaving or degrading RNA substrates. They preferentially cleave single-stranded RNA molecules between purine and uridine residues to generate two nucleotide fragments with 2'3'-cyclic phosphate adenosine/guanosine terminus and uridine residue, respectively. Accumulating studies have revealed that RNase T2 is critical for the pathophysiology of inflammation and cancer. In this review, we introduce the distribution, structure, and functions of RNase T2, its differential roles in inflammation and cancer, and the perspective for its research and related applications in medicine.


Subject(s)
Disease Susceptibility , Endoribonucleases/genetics , Endoribonucleases/metabolism , Inflammation/etiology , Inflammation/metabolism , Neoplasms/etiology , Neoplasms/metabolism , Animals , Biomarkers , Cellular Microenvironment/immunology , Disease Susceptibility/immunology , Endoribonucleases/chemistry , Humans , Immune System/immunology , Immune System/metabolism , Immunomodulation , Inflammation/pathology , Neoplasms/pathology , Structure-Activity Relationship
16.
Mol Cancer ; 20(1): 52, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1136226

ABSTRACT

In vitro-transcribed messenger RNA-based therapeutics represent a relatively novel and highly efficient class of drugs. Several recently published studies emphasize the potential efficacy of mRNA vaccines in treating different types of malignant and infectious diseases where conventional vaccine strategies and platforms fail to elicit protective immune responses. mRNA vaccines have lately raised high interest as potent vaccines against SARS-CoV2. Direct application of mRNA or its electroporation into dendritic cells was shown to induce polyclonal CD4+ and CD8+ mediated antigen-specific T cell responses as well as the production of protective antibodies with the ability to eliminate transformed or infected cells. More importantly, the vaccine composition may include two or more mRNAs coding for different proteins or long peptides. This enables the induction of polyclonal immune responses against a broad variety of epitopes within the encoded antigens that are presented on various MHC complexes, thus avoiding the restriction to a certain HLA molecule or possible immune escape due to antigen-loss. The development and design of mRNA therapies was recently boosted by several critical innovations including the development of technologies for the production and delivery of high quality and stable mRNA. Several technical obstacles such as stability, delivery and immunogenicity were addressed in the past and gradually solved in the recent years.This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.


Subject(s)
Cancer Vaccines/genetics , Cancer Vaccines/immunology , Neoplasms/etiology , Neoplasms/therapy , RNA, Messenger/genetics , RNA, Messenger/immunology , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Cancer Vaccines/administration & dosage , Drug Delivery Systems , Gene Expression Regulation, Neoplastic , Gene Transfer Techniques , Humans , Immunity , Immunotherapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasms/pathology , RNA Stability , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
17.
Mol Oncol ; 15(3): 801-808, 2021 03.
Article in English | MEDLINE | ID: covidwho-1117325

ABSTRACT

Traditionally, the prevention of cancer (and other chronic diseases) has been considered primarily linked to personal responsibility, for which interventions must be based on health education information enabling individuals to make knowledge-based decisions to improve their lifestyle. However, lifestyle is conditioned by environmental factors (including dimensions such as the context of economics, transport, urbanism, agriculture or education) that may render healthy behavioural choices either easier or, alternatively, impossible. This article reviews the conceptual underpinnings of the behavioural-structural dichotomy. We believe that it is advisable to opt for multilevel strategies that take into account all the determinants of health, using structural and behavioural approaches, rather than only the latter, as has been done until now.


Subject(s)
Neoplasms/prevention & control , Health Behavior , Humans , Life Style , Neoplasms/etiology , Protective Factors , Risk Factors , Sustainable Development
18.
Virologie (Montrouge) ; 24(6): 381-418, 2020 12 01.
Article in French | MEDLINE | ID: covidwho-1030336

ABSTRACT

The innate immune response is nonspecific and constitutes the first line of defense against infections by pathogens, mainly by enabling their elimination by phagocytosis or apoptosis. In immune cells, this response is characterized, amongst others, by the synthesis of restriction factors, a class of proteins whose role is to inhibit viral replication. Among them, the proteins of the APOBEC3 (Apolipoprotein B mRNA-editing Enzyme Catalytic polypeptide-like 3 or A3) family are major antiviral factors that target a wide range of viruses. One of their targets is the Human Immunodeficiency Virus Type 1 (HIV-1): the deaminase activity of some A3 proteins converts a fraction of cytidines of the viral genome into uridines, impairing its expression. Nevertheless, HIV-1 counteracts A3 proteins thanks to its Vif protein, which inhibits them by hijacking several cellular mechanisms. Besides, APOBEC3 proteins help maintaining the genome integrity by inhibiting retroelements but they also contribute to carcinogenesis, as it is the case for A3A and A3B, two major factors in this process. The large range of A3 activities, combined with recent studies showing their implication in the regulation of emerging viruses (Zika, SARS-CoV-2), allow A3 and their viral partners to be considered as therapeutic areas.


Subject(s)
APOBEC Deaminases/physiology , COVID-19/immunology , Immunity, Innate , Adult , Amino Acid Motifs , Animals , Cell Cycle Proteins/metabolism , Cytidine Deaminase/physiology , DNA Repair , DNA, Viral/metabolism , Deamination , Humans , Mammals/metabolism , MicroRNAs/genetics , Models, Molecular , Molecular Targeted Therapy , Mutagenesis , Neoplasms/enzymology , Neoplasms/etiology , Neoplasms/genetics , Prognosis , Protein Conformation , RNA Editing , Structure-Activity Relationship , Transcription, Genetic , Viral Proteins/metabolism , Virus Diseases/drug therapy , Virus Diseases/enzymology , Virus Diseases/immunology , Virus Replication
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