scholarly journals ZIKV Infection and miRNA Network in Pathogenesis and Immune Response

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1992
Author(s):  
Carolina Manganeli Polonio ◽  
Jean Pierre Schatzmann Peron
Keyword(s):  
Transcriptional Repression ◽  
Neuronal Development ◽  
Viral Infections ◽  
Protein Translation ◽  
Neurological Impairment ◽  
Severe Illness ◽  
Biological Processes ◽  
Mosquito Vectors ◽  
Zikv Infection ◽  
Neuronal Precursor Cells

Over the years, viral infections have caused severe illness in humans. Zika Virus (ZIKV) is a flavivirus transmitted by mosquito vectors that leads to notable neurological impairment, whose most dramatic impact is the Congenital ZIKV Syndrome (CZS). ZIKV targets neuronal precursor cells leading to apoptosis and further impairment of neuronal development, causing microcephaly, lissencephaly, ventriculomegaly, and calcifications. Several regulators of biological processes are involved in CZS development, and in this context, microRNAs (miRNAs) seem to have a fundamental role. miRNAs are important regulators of protein translation, as they form the RISC silencing complex and interact with complementary mRNA target sequences to further post-transcriptional repression. In this context, little is known about their participation in the pathogenesis of viral infections. In this review, we discuss how miRNAs could relate to ZIKV and other flavivirus infections.

scholarly journals Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Najeh Hcini ◽  
Yaovi Kugbe ◽  
Zo Hasina Linah Rafalimanana ◽  
Véronique Lambert ◽  
Meredith Mathieu ◽  
...  
Keyword(s):  
Neurological Impairment ◽  
In Utero ◽  
In Utero Exposure ◽  
Zikv Infection ◽  
Neurodevelopmental Delay ◽  
Systematic Testing ◽  
Brain Anomalies ◽  
Increased Risk ◽  
Structural Brain

AbstractLittle is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5–29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2–20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9–10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

scholarly journals Emerging multifaceted roles of BAP1 complexes in biological processes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aileen Patricia Szczepanski ◽  
Lu Wang
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Multiprotein Complex ◽  
Downstream Target ◽  
Evolutionarily Conserved ◽  
Complex Forms ◽  
Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

scholarly journals Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6047
Author(s):  
Mattias F. Lindberg ◽  
Laurent Meijer
Keyword(s):  
Tyrosine Phosphorylation ◽  
Human Disease ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Viral Infections ◽  
Current Knowledge ◽  
Lymphoblastic Leukemia ◽  
Cell Cycle Control ◽  
Megakaryoblastic Leukemia ◽  
Dual Specificity

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.

Gene of the month: BECN1

2014 ◽  
Vol 67 (8) ◽  
pp. 656-660 ◽  
Author(s):  
Sumit Sahni ◽  
Angelica M Merlot ◽  
Sukriti Krishan ◽  
Patric J Jansson ◽  
Des R Richardson
Keyword(s):  
Neurological Disorders ◽  
Viral Infections ◽  
Critical Role ◽  
Beclin 1 ◽  
Biological Processes ◽  
Disease States ◽  
Binding Partners ◽  
Future Drug ◽  
Cellular Components ◽  
Important Therapeutic Target

The BECN1 gene encodes the Beclin-1 protein, which is a well-established regulator of the autophagic pathway. It is a mammalian orthologue of the ATG6 gene in yeast and was one of the first identified mammalian autophagy-associated genes. Beclin-1 interacts with a number of binding partners in the cell which can lead to either activation (eg, via PI3KC3/Vps34, Ambra 1, UV radiation resistance-associated gene) or inhibition (eg, via Bcl-2, Rubicon) of the autophagic pathway. Apart from its role as a regulator of autophagy, it is also shown to effect important biological processes in the cell such as apoptosis and embryogenesis. Beclin-1 has also been implicated to play a critical role in the pathology of a variety of disease states including cancer, neurological disorders (eg, Alzheimer's disease, Parkinson's disease) and viral infections. Thus, understanding the functions of Beclin-1 and its interactions with other cellular components will aid in its development as an important therapeutic target for future drug development.

scholarly journals Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

2021 ◽  
Author(s):  
Elizabeth E. McCarthy ◽  
Pamela M. Odorizzi ◽  
Emma Lutz ◽  
Carolyn P. Smullin ◽  
Iliana Tenvooren ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Zikv Infection ◽  
Antibody Titers ◽  
Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

scholarly journals Impact of Zika Virus Infection on Human Neural Stem Cell MicroRNA Signatures

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1219
Author(s):  
Denna Tabari ◽  
Catharina Scholl ◽  
Michael Steffens ◽  
Sandra Weickhardt ◽  
Fabian Elgner ◽  
...  
Keyword(s):  
Zika Virus ◽  
Viral Infections ◽  
Cell Communication ◽  
French Polynesia ◽  
Host Responses ◽  
Zikv Infection ◽  
Regulate Gene Expression ◽  
Mediate Cell ◽  
And Oxidative Stress ◽  
Mrna Transcriptome

Zika virus (ZIKV) is a mosquito-borne virus, which can cause brain abnormalities in newborns, including microcephaly. MicroRNAs (miRNAs) are small non-coding RNAs, which post- transcriptionally regulate gene expression. They are involved in various processes including neurological development and host responses to viral infection, but their potential role in ZIKV pathogenesis remains poorly understood. MiRNAs can be incorporated into extracellular vesicles (EVs) and mediate cell-to-cell communication. While it is well known that in viral infections EVs carrying miRNAs can play a crucial role in disease pathogenesis, ZIKV effects on EV-delivered miRNAs and their contribution to ZIKV pathogenesis have not been elucidated. In the present study, we profiled intracellular and EV-derived miRNAs by next generation sequencing and analyzed the host mRNA transcriptome of neural stem cells during infection with ZIKV Uganda and French Polynesia strains. We identified numerous miRNAs, including miR-4792, which were dysregulated at the intracellular level and had altered levels in EVs during ZIKV infection. Integrated analyses of differentially expressed genes and miRNAs showed that ZIKV infection had an impact on processes associated with neurodevelopment and oxidative stress. Our results provide insights into the roles of intracellular and EV-associated host miRNAs in ZIKV pathogenesis.

scholarly journals miRNA-Mediated Interactions in and between Plants and Insects

2018 ◽  
Vol 19 (10) ◽  
pp. 3239 ◽  
Author(s):  
Chade Li ◽  
Annette Wong ◽  
Shuang Wang ◽  
Qi Jia ◽  
Wen-Po Chuang ◽  
...  
Keyword(s):  
Regulation Of Gene Expression ◽  
Protein Translation ◽  
Review Article ◽  
Biological Processes ◽  
Critical Area ◽  
Biotechnological Applications ◽  
Mirna Regulation ◽  
Cellular Regulation ◽  
Plant Insect Interactions ◽  
Insect Interactions

Our understanding of microRNA (miRNA) regulation of gene expression and protein translation, as a critical area of cellular regulation, has blossomed in the last two decades. Recently, it has become apparent that in plant-insect interactions, both plants and insects use miRNAs to regulate their biological processes, as well as co-opting each others’ miRNA systems. In this review article, we discuss the current paradigms of miRNA-mediated cellular regulation and provide examples of plant-insect interactions that utilize this regulation. Lastly, we discuss the potential biotechnological applications of utilizing miRNAs in agriculture.

High Levels of Circulating Cell-free DNA Are Associated With a Poor Prognosis in Patients With Severe Fever With Thrombocytopenia Syndrome

2019 ◽  
Vol 70 (9) ◽  
pp. 1941-1949 ◽  
Author(s):  
Yue Zhang ◽  
Rui Song ◽  
Yi Shen ◽  
Yongxiang Zhao ◽  
Zhenghua Zhao ◽  
...  
Keyword(s):  
Disease Progression ◽  
Predictive Value ◽  
Viral Infections ◽  
Myocardial Damage ◽  
Predictive Biomarker ◽  
Severe Illness ◽  
Dna Complexes ◽  
Cell Free Dna ◽  
Free Dna ◽  
Severe Fever

AbstractBackgroundThe extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS.MethodsA prospective study was performed with a multicenter cohort of patients with SFTS (n = 112) to quantify serum NET levels. Three markers of NETs—namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes—were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels.ResultsSFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. A high level of cfDNA (>711.7 ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049–33.503]; P = .003).ConclusionsThis study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.

scholarly journals microRNA seedless sites attenuate strong-seed-site-mediated target repression

2019 ◽  
Author(s):  
Xujun Wang ◽  
Jingru Tian ◽  
Peng Cui ◽  
Stephen Mastriano ◽  
Dingyao Zhang ◽  
...  
Keyword(s):  
Protein Translation ◽  
Untranslated Regions ◽  
Seed Region ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Attenuation Effect ◽  
Reporter Assays ◽  
Regulate Protein ◽  
Surprising Finding

AbstractMicroRNAs (miRNAs) regulate protein-coding gene expression primarily through cognitive binding sites in the 3’ untranslated regions (3′ UTRs). Seed sites are sequences in messenger RNAs (mRNAs) that form perfect Watson-Crick base-paring with a miRNA’s seed region, which can effectively reduce mRNA abundance and/or repress protein translation. Some seedless sites, which do no form perfect seed-pairing with a miRNA, can also lead to target repression, often with lower efficacy. Here we report the surprising finding that when seedless sites and seed sites are co-present in the same 3’UTR, seedless sites attenuate strong-seed-site-mediated target suppression, independent of 3′ UTR length. This attenuation effect is detectable in >70% of transcriptomic datasets examined, in which specific miRNAs are experimentally increased or decreased. The attenuation effect is confirmed by 3’UTR reporter assays and mediated through base-pairing between miRNA and seedless sites. Furthermore, this seedless-site-based attenuation effect could affect seed sites of the same miRNA or another miRNA, thus partially explaining the variability in target suppression and miRNA-mediated gene upregulation. Our findings reveal an unexpected principle of miRNA-mediated gene regulation, and could impact the understanding of many miRNA-regulated biological processes.

scholarly journals Neurodevelopmental outcomes of infants secondary to in utero exposure to maternal SARS-CoV-2 infection: A national prospective study in Kuwait

2021 ◽  
Author(s):  
Mariam Ayed ◽  
Alia Embaireeg ◽  
Mais Kartam ◽  
Kiran More ◽  
Mafaza Alqallaf ◽  
...  
Keyword(s):  
Developmental Delays ◽  
Viral Infections ◽  
Cutoff Score ◽  
Third Trimester ◽  
Post Discharge ◽  
Neurodevelopmental Outcomes ◽  
Population Mean ◽  
Neuronal Precursor Cells ◽  
Ages And Stages Questionnaire

Background An increasing proportion of women are being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study is to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy. Methods In this prospective cohort study, the neurodevelopment status of infants (N=298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff score: ≤2 standard deviations (SDs) below the population mean) and no delay (score >2 SDs above the population mean). Results Approximately 10% of infants born to mothers with SARS-CoV-2 infections during pregnancy showed developmental delays. Two of 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infection during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P=0.039) and second trimesters (P=0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. Infants born at <31 weeks gestation were more prone to developmental delays than those born at >31 weeks gestation (10% versus 0.8%; P=0.002). Conclusion The findings of the study highlight the need for long-term neurodevelopmental assessment of infants born to mothers with SARS-CoV-2 infection.

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