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1.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334813

ABSTRACT

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART- naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans, yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced “Trojan Horse” in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage “Trojan Horse”, myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

2.
Expert Review of Respiratory Medicine ; 16(3):253-255, 2022.
Article in English | EMBASE | ID: covidwho-1815893
3.
Biochemical and Cellular Archives ; 21(2):1-2, 2021.
Article in English | EMBASE | ID: covidwho-1812557
4.
Blood Purification ; 50(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1812556

ABSTRACT

The proceedings contain 33 papers. The topics discussed include: acute kidney injury in children and adolescents hospitalized for diabetic ketoacidosis;urinary biomarkers as predictors of AKI in COVID-19 hospitalized patients with pneumonia;critically ill patients with COVID-19 pneumonia requiring renal replacement therapy with Oxiris membrane in a third level hospital in north-east Mexico;legionellosis followed by acute respiratory distress syndrome successfully treated with antibiotics and polymyxin B hemoperfusion therapy;the role of serum miRNA in leptospirosis-associated acute kidney injury;and polymixin B hemoperfusion in patients with COVID-19 infection and endotoxin shock: a case report.

5.
Mol Biol ; 56(1):29-45, 2022.
Article in English | PubMed | ID: covidwho-1807339

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) warrants the identification of factors that may determine both risk and severity of infection. The factors include microRNAs that have a wide regulatory potential and hence are particularly interesting. The review focuses on the potential roles of human microRNAs and the viral genome as well as microRNAs in SARS-CoV-2 infection and clinical features of COVID-19. The review summarizes the information about the human microRNAs that are thought to specifically bind to the SARS-CoV-2 genome and considers their expression levels in various organs (cells) in both healthy state and pathologies that are risk factors for severe COVID-19. Potential mechanisms whereby SARS-CoV-2 may affect the clinical features of COVID-19 are discussed in brief. The mechanisms include blocking of human microRNAs and RNA-binding proteins, changes in gene expression in infected cells, and possible epigenetic modifications of the human genome with the participation of coronavirus microRNAs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1134/S0026893322010034.

6.
Front Pharmacol ; 12: 765553, 2021.
Article in English | MEDLINE | ID: covidwho-1785387

ABSTRACT

COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.

7.
Front Immunol ; 13: 825103, 2022.
Article in English | MEDLINE | ID: covidwho-1785336

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on the world, affecting people's lifestyle, economy, and livelihood. Recently, with the development of vaccines, the number of infected cases has decreased. Many case reports have revealed that COVID-19 may induce other serious comorbidities such as anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis. Anti-NMDA receptor encephalitis is an acute autoimmune disease that occurs more commonly in women than in men. To explore the association between COVID-19 and anti-NMDA receptor encephalitis, the microRNA (miRNA) biomarkers of COVID-19, anti-NMDA receptor encephalitis, and other related diseases from the literature are reviewed; then on the basis of these miRNA biomarkers, the relationship between COVID-19 and anti-NMDA receptor encephalitis is discussed. miRNAs are small non-coding RNAs that play important roles in cell differentiation, development, cell-cycle regulation, and apoptosis. miRNAs have been used as biological biomarkers for many diseases. The results in this study reveal that the relationship between anti-NMDA receptor encephalitis and COVID-19 infection or COVID-19 vaccination cannot be excluded; however, the risk that COVID-19 triggers the anti-NMDA receptor encephalitis is not high.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , COVID-19 , MicroRNAs , Biomarkers , COVID-19 Vaccines , Female , Humans , Male , MicroRNAs/genetics
8.
EBioMedicine ; 78: 103982, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1783293

ABSTRACT

BACKGROUND: Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe coronavirus disease 2019 (COVID-19), indicating that the vasculature is affected during the acute stages of SARS-CoV-2 infection. It remains unknown whether circulating vascular markers are sufficient to predict clinical outcomes, are unique to COVID-19, and if vascular permeability can be therapeutically targeted. METHODS: Prospectively evaluating the prevalence of circulating inflammatory, cardiac, and EC activation markers as well as developing a microRNA atlas in 241 unvaccinated patients with suspected SARS-CoV-2 infection allowed for prognostic value assessment using a Random Forest model machine learning approach. Subsequent ex vivo experiments assessed EC permeability responses to patient plasma and were used to uncover modulated gene regulatory networks from which rational therapeutic design was inferred. FINDINGS: Multiple inflammatory and EC activation biomarkers were associated with mortality in COVID-19 patients and in severity-matched SARS-CoV-2-negative patients, while dysregulation of specific microRNAs at presentation was specific for poor COVID-19-related outcomes and revealed disease-relevant pathways. Integrating the datasets using a machine learning approach further enhanced clinical risk prediction for in-hospital mortality. Exposure of ECs to COVID-19 patient plasma resulted in severity-specific gene expression responses and EC barrier dysfunction, which was ameliorated using angiopoietin-1 mimetic or recombinant Slit2-N. INTERPRETATION: Integration of multi-omics data identified microRNA and vascular biomarkers prognostic of in-hospital mortality in COVID-19 patients and revealed that vascular stabilizing therapies should be explored as a treatment for endothelial dysfunction in COVID-19, and other severe diseases where endothelial dysfunction has a central role in pathogenesis. FUNDING INFORMATION: This work was directly supported by grant funding from the Ted Rogers Center for Heart Research, Toronto, Ontario, Canada and the Peter Munk Cardiac Center, Toronto, Ontario, Canada.

9.
Science ; 373(6558):977.13-979, 2021.
Article in English | EMBASE | ID: covidwho-1769812
10.
Journal of Oral and Maxillofacial Surgery ; 79(10):e95, 2021.
Article in English | EMBASE | ID: covidwho-1768349

ABSTRACT

Rationale: Smoking electronic cigarettes (e-cigarettes) is increasing in popularity, but little information is available as to the biologic consequences to the cell populations impacted by the e-cigarette smoke. Based on the knowledge that the oral epithelium is the initial site exposed to e-cigarette smoke, the authors assessed the hypothesis that e-cigarette smoking modifies the biology of oral epithelium of healthy e-cigarette smokers. Methods: Oral biopsies of n = 23 healthy nonsmoker controls and n= 24 healthy e-cigarette smokers (e-cigarette smokers for an average of 2.0±1.0 years) matched for age, gender, and ethnicity were compared based on pathology and RNA transcriptome (mRNA and miRNA) using Illumina Hi-Seq 2000 sequencing. The mRNA data were assessed in e-cigarette smokers compared to nonsmokers genome-wide (n = 19,724): genes previously identified as significantly dysregulated in the oral epithelium of e-cigarette smokers vs. nonsmokers (n = 758);genes previously identified as significantly dysregulated in the small airway epithelium of nonsmokers following an acute exposure to e-cigarettes (n = 71);and genes related to the initial steps of COVID-19 infection, including ACE2, the COVID-19 receptor (n = 9). The miRNA of e-cigarette smokers and nonsmokers was compared on a genome-wide basis (n = 1,100 mature and human miRNAs). All comparisons were performed using ANOVA, Benajmini-Hochberg corrected. P value <.05 was considered significant. Results: The morphology of the epithelium and lamina propria in e-cigarette smokers was normal, with no thickening of the epithelium, dysplasia, basilar hyperplasia, dyskeratosis, and no abnormal vascularity or inflammatory infiltration. The basilar layer in e-cigarette smokers appeared normal, with normal mitotic activity and no nuclear pleomorphism. Assessment of the transcriptome, both on mRNA and miRNA levels, based on all gene lists did not identify any genes significantly modified in the oral epithelium of e-cigarette smokers compared to nonsmokers. Conclusion: The oral epithelium pathology and transcriptome of e-cigarette smokers are not modified in response to e-cigarette smoking.

11.
Cancers (Basel) ; 14(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1760403

ABSTRACT

Traditional targeted therapeutic agents have relied on small synthetic molecules or large proteins, such as monoclonal antibodies. These agents leave a lot of therapeutic targets undruggable because of the lack or inaccessibility of active sites and/or pockets in their three-dimensional structure that can be chemically engaged. RNA presents an attractive, transformative opportunity to reach any genetic target with therapeutic intent. RNA therapeutic design is amenable to modularity and tunability and is based on a computational blueprint presented by the genetic code. Here, we will focus on short non-coding RNAs (sncRNAs) as a promising therapeutic modality because of their potency and versatility. We review recent progress towards clinical application of small interfering RNAs (siRNAs) for single-target therapy and microRNA (miRNA) activity modulators for multi-target therapy. siRNAs derive their potency from the fact that the underlying RNA interference (RNAi) mechanism is catalytic and reliant on post-transcriptional mRNA degradation. Therapeutic siRNAs can be designed against virtually any mRNA sequence in the transcriptome and specifically target a disease-causing mRNA variant. Two main classes of microRNA activity modulators exist to increase (miRNA mimics) or decrease (anti-miRNA inhibitors) the function of a specific microRNA. Since a single microRNA regulates the expression of multiple target genes, a miRNA activity modulator can have a more profound effect on global gene expression and protein output than siRNAs do. Both types of sncRNA-based drugs have been investigated in clinical trials and some siRNAs have already been granted FDA approval for the treatment of genetic, cardiometabolic, and infectious diseases. Here, we detail clinical results using siRNA and miRNA therapeutics and present an outlook for the potential of these sncRNAs in medicine.

12.
European Urology ; 79:S909, 2021.
Article in English | EMBASE | ID: covidwho-1747421

ABSTRACT

Introduction & Objectives: In November 2019 the first case of Sars-Cov2 was noticed in Wuhan, China. This virus was finally spreading all over the world and we have a pandemic situation with an unclear outcome. Several different groups have already published that the virus can be present in the testis after infection, however with unknown consequences. Materials & Methods: FPPE tissue samples from patients died with or of Corona (n=6) compared with healthy donors (n=5), seminoma without metastasis (n=5) and seminoma with metastasis (n=5) were analyzed and compared via qRT-PCR for the expression of microRNAs (miRs) which are predominantly overexpressed in Seminoma and in metastazing cells, miR-199-3p, miR-498 and miR-371a-3p. Beyond this, an IHC for Androgenreceptor (AR) and ACE2 was performed. The median age of the corona patients was 70 years. Results: In 50% of all corona FFPE samples, a significant upregulation of the seminoma specific miR-371a-3p was detectable, whereas all other tumor specific miRs were negative. In H&E staining of the FFPE samples in 50% of all patients the spermatogenesis was reduced/absent. IHC for AR in COVID positive and negative testes showed loss of immunoreactivity in Sertoli cells of Covid-positive cases vs controls. Conclusions: Our group presented here for the first time a possible late onset complication after Sars-Cov2 infection, namely the increased risk for developing seminoma due to the upregulation of the seminoma specific miR-371a-3p.

13.
Indian Journal of Medical Microbiology ; 39:S70, 2021.
Article in English | EMBASE | ID: covidwho-1734506

ABSTRACT

Background: The Coronavirus disease 2019 (COVID -19), an infectious disease caused by newly discovered Novel Coro- navirus. COVID-19 has spread worldwide causing a pandemic, with maximum death -cases. Hence there is an urgent need for vaccines and treatments to be developed to combat the COVID -19. To overcome this Micro RNA (miRNA) based therapy will be an effective option in controlling infection. The miRNA is a noncoding single -stranded RNA that is smaller in size (17-24nucleotides). They are also able to regulate the Gut Microbiota, an essential factor of host immune response. The usage of miRNA instead of other techniques has many advantages that include early detection, improved pathogen identification, detection of latent infection, personalized medicine. Methods: Selective COVID 19 genome sequences with special reference from India by NCBI genome database and Nextstrain.org. Coronavirus subtyping and Mutation analysis carried out by Genome Detective Coronavirus Typing Tool (version 1.1.3) and CLUSTAL OMEGA software. The prediction of antiviral miRNA are performed online by Tar- getscan.org Results: This study integrated selective bioinformatics tools and databases to investigate the COVID -19 sequences in India and the trialogue relationship between the miRNA with Coronavirus and Gut Microbiota. The miRNA is found to be a potential biomarker and also therapeutics for diseases in viral diseases. Conclusions: The miRNA has been extensively documented for their key roles in combating the disease and it is still an unexplored area. As the miRNA regulates the gene of the target, altering the expression can bring in a desired therapeu- tic outcome.

14.
Clin Exp Pediatr ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1725368

ABSTRACT

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently US Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

15.
Zeitschrift fur Gastroenterologie ; 60(1):e45, 2022.
Article in English | EMBASE | ID: covidwho-1721712

ABSTRACT

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current coronavirus disease 2019 (COVID-19) pandemic. Despite a preferential respiratory tropism of SARS-CoV-2, multi-organ involvement has been described. SARS-CoV-2 entry into host cells is mediated by the entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Recent studies suggest that SARS-CoV-2 causes direct hepatic impairment in COVID-19 patients. Interestingly, ACE2 and TMPRSS2 are also expressed in primary human hepatocytes (PHH). Despite this evidence, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHHs are scarce. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been described to modulate various cellular processes and have been implicated as potential therapeutic target. We aimed to study the infection of PHHs with SARS-CoV-2 and to evaluate the potential of miRNAs for modulating viral infection. We could demonstrate that PHHs can be readily infected with SARS-CoV-2. Bioinformatics analyses revealed miR- 200c-3p, miR-429, let-7c-5p and miR-141-3p as candidate miRNAs targeting ACE2 and TMPRSS2. All miRNAs were able to reduce SARS-CoV-2 burden in PHH by supressing ACE2 and TMPRSS2. Our findings provide the first evidence of the applicability of miRNA molecules in reducing SARS-CoV-2 viral loads.

16.
Front Med (Lausanne) ; 8: 756517, 2021.
Article in English | MEDLINE | ID: covidwho-1703379

ABSTRACT

Background: The pathophysiology of COVID-19-related critical illness is not completely understood. Here, we analyzed the microRNA (miRNA) profile of bronchial aspirate (BAS) samples from COVID-19 and non-COVID-19 patients admitted to the ICU to identify prognostic biomarkers of fatal outcomes and to define molecular pathways involved in the disease and adverse events. Methods: Two patient populations were included (n = 89): (i) a study population composed of critically ill COVID-19 and non-COVID-19 patients; (ii) a prospective study cohort composed of COVID-19 survivors and non-survivors among patients assisted by invasive mechanical ventilation (IMV). BAS samples were obtained by bronchoaspiration during the ICU stay. The miRNA profile was analyzed using RT-qPCR. Detailed biomarker and bioinformatics analyses were performed. Results: The deregulation in five miRNA ratios (miR-122-5p/miR-199a-5p, miR-125a-5p/miR-133a-3p, miR-155-5p/miR-486-5p, miR-214-3p/miR-222-3p, and miR-221-3p/miR-27a-3p) was observed when COVID-19 and non-COVID-19 patients were compared. In addition, five miRNA ratios segregated between ICU survivors and nonsurvivors (miR-1-3p/miR-124-3p, miR-125b-5p/miR-34a-5p, miR-126-3p/miR-16-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). Through multivariable analysis, we constructed a miRNA ratio-based prediction model for ICU mortality that optimized the best combination of miRNA ratios (miR-125b-5p/miR-34a-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). The model (AUC 0.85) and the miR-199a-5p/miR-9-5p ratio (AUC 0.80) showed an optimal discrimination value and outperformed the best clinical predictor for ICU mortality (days from first symptoms to IMV initiation, AUC 0.73). The survival analysis confirmed the usefulness of the miRNA ratio model and the individual ratio to identify patients at high risk of fatal outcomes following IMV initiation. Functional enrichment analyses identified pathological mechanisms implicated in fibrosis, coagulation, viral infections, immune responses and inflammation. Conclusions: COVID-19 induces a specific miRNA signature in BAS from critically ill patients. In addition, specific miRNA ratios in BAS samples hold individual and collective potential to improve risk-based patient stratification following IMV initiation in COVID-19-related critical illness. The biological role of the host miRNA profiles may allow a better understanding of the different pathological axes of the disease.

17.
Mech Ageing Dev ; 202: 111636, 2022 03.
Article in English | MEDLINE | ID: covidwho-1665255

ABSTRACT

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.


Subject(s)
COVID-19/blood , COVID-19/mortality , Circulating MicroRNA/blood , Hospital Mortality , Hospitalization , MicroRNAs/blood , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/genetics , Circulating MicroRNA/genetics , Female , Humans , Male , MicroRNAs/genetics , Predictive Value of Tests , Prognosis , RNA-Seq , Risk Assessment , Risk Factors , Time Factors , Up-Regulation
18.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1632481

ABSTRACT

Introduction: Neuropilin-1 has been recently identified as a co-factor needed for the entry of SARSCoV-2 in host cells and has been linked to neurologic symptoms of COVID-19 (Science 2020). Emerging evidence indicates that exosomal microRNAs (miRNAs) are involved in a number of physiologic and pathologic processes. However, to our knowledge, exosomal miRNAs have not been hitherto investigated in COVID-19. Hypothesis: Since we have recently demonstrated that miR-24 targets the 3'UTR of the gene encoding for Neuropilin-1 and this miRNA is expressed in human brain endothelial cells, we hypothesized an association between plasma levels of CD31 extracellular vesicles (EVs) enriched in miR-24 and the risk of cerebrovascular manifestations in patients hospitalized for COVID-19. Methods and Results: We obtained plasma from >300 COVID-19 patients;as control COVID-19 negative populations, we obtained plasma from healthy donors and patients hospitalized for cerebrovascular disorders. CD31 EVs were isolated from plasma on hospital admission, and miR24 levels were quantified. When comparing patients with vs without cerebrovascular disorders, we found that plasma levels of CD31 EV miR-24 were significantly different between these populations. We did not find any significant difference among groups when assessing circulating free levels of miR-24. Using a multiple regression analysis, adjusting for age, hypertension, and diabetes, the association between EV miR-24 and cerebrovascular complications in COVID-19 patients was confirmed (P<0.05). Conclusions: This is the first study showing a significant association between EV non-coding RNAs and clinical outcome in COVID-19 patients. Our results are relevant for basic researchers, because we identified an unprecedented significant association between EV miR-24 and cerebrovascular disorders, which could be helpful to better understand the molecular mechanisms underlying the pathophysiology of cerebrovascular events in COVID-19, as well as for clinicians, inasmuch as this association may help healthcare professionals in identifying COVID-19 patients who are at high risk of developing cerebrovascular disease.

19.
Front Immunol ; 12: 767726, 2021.
Article in English | MEDLINE | ID: covidwho-1639598

ABSTRACT

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus-host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.


Subject(s)
Genetic Predisposition to Disease/genetics , Immune Evasion/genetics , Interferon Type I/genetics , SARS-CoV-2/genetics , 2',5'-Oligoadenylate Synthetase/genetics , COVID-19/pathology , Cell Line , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/immunology , Interferon Regulatory Factor-7/genetics , Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/immunology , STAT2 Transcription Factor/genetics
20.
Cell Mol Life Sci ; 79(2): 75, 2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1630170

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new member of the Betacoronaviridae family, responsible for the recent pandemic outbreak of COVID-19. To start exploring the molecular events that follow host cell infection, we queried VirusCircBase and identified a circular RNA (circRNA) predicted to be synthesized by SARS-CoV-2, circ_3205, which we used to probe: (i) a training cohort comprised of two pools of cells from three nasopharyngeal swabs of SARS-CoV-2 infected (positive) or uninfected (negative, UCs) individuals; (ii) a validation cohort made up of 12 positive and 3 negative samples. The expression of circRNAs, miRNAs and miRNA targets was assayed through real-time PCR. CircRNA-miRNA interactions were predicted by TarpMiR, Analysis of Common Targets for circular RNAs (ACT), and STarMir tools. Enrichment of the biological processes and the list of predicted miRNA targets were retrieved from DIANA miRPath v3.0. Our results showed that the predicted SARS-CoV-2 circ_3205 was expressed only in positive samples and its amount positively correlated with that of SARS-CoV-2 Spike (S) mRNA and the viral load (r values = 0.80952 and 0.84867, Spearman's correlation test, respectively). Human (hsa) miR-298 was predicted to interact with circ_3205 by all three predictive tools. KCNMB4 and PRKCE were predicted as hsa-miR-298 targets. Interestingly, the function of both is correlated with blood coagulation and immune response. KCNMB4 and PRKCE mRNAs were upregulated in positive samples as compared to UCs (6 and 8.1-fold, p values = 0.049 and 0.02, Student's t test, respectively) and their expression positively correlated with that of circ_3205 (r values = 0.6 and 0.25, Spearman's correlation test, respectively). We propose that our results convincingly suggest that circ_3205 is a circRNA synthesized by SARS-CoV-2 upon host cell infection and that it may behave as a competitive endogenous RNA (ceRNA), sponging hsa-miR-298 and contributing to the upregulation of KCNMB4 and PRKCE mRNAs.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , RNA, Circular/genetics , RNA, Viral , SARS-CoV-2/genetics , Computational Biology , Gene Expression Regulation, Viral , Gene Regulatory Networks , Humans , Large-Conductance Calcium-Activated Potassium Channel beta Subunits/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Nasopharynx/virology , Nerve Tissue Proteins/genetics , Protein Interaction Mapping , Protein Kinase C-epsilon/genetics , Reproducibility of Results
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