scholarly journals A Message from the Human Placenta: Structural and Immunomodulatory Defense against SARS-CoV-2

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1777 ◽  
Author(s):  
Nina-Naomi Kreis ◽  
Andreas Ritter ◽  
Frank Louwen ◽  
Juping Yuan
Keyword(s):  
Vertical Transmission ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Preterm Births ◽  
Nuclear Factor Κb ◽  
Immune Defense ◽  
Global Public Health ◽  
Health Crisis ◽  
Host Interactions ◽  
Tissue Damages

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic has caused a global public health crisis. Viral infections may predispose pregnant women to a higher rate of pregnancy complications, including preterm births, miscarriage and stillbirth. Despite reports of neonatal COVID-19, definitive proof of vertical transmission is still lacking. In this review, we summarize studies regarding the potential evidence for transplacental transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterize the expression of its receptors and proteases, describe the placental pathology and analyze virus-host interactions at the maternal-fetal interface. We focus on the syncytium, the barrier between mother and fetus, and describe in detail its physical and structural defense against viral infections. We further discuss the potential molecular mechanisms, whereby the placenta serves as a defense front against pathogens by regulating the interferon type III signaling, microRNA-triggered autophagy and the nuclear factor-κB pathway. Based on these data, we conclude that vertical transmission may occur but rare, ascribed to the potent physical barrier, the fine-regulated placental immune defense and modulation strategies. Particularly, immunomodulatory mechanisms employed by the placenta may mitigate violent immune response, maybe soften cytokine storm tightly associated with severely ill COVID-19 patients, possibly minimizing cell and tissue damages, and potentially reducing SARS-CoV-2 transmission.

scholarly journals MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2525
Author(s):  
Jorlan Fernandes ◽  
Renan Lyra Miranda ◽  
Elba Regina Sampaio de Lemos ◽  
Alexandro Guterres
Keyword(s):  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Mirna Expression Profile ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Emerging Viruses ◽  
Cellular Mirnas ◽  
Host Interactions ◽  
Causative Agents

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

scholarly journals Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection

2021 ◽  
Author(s):  
Wenzhe Wu ◽  
Eun-Jin Choi ◽  
Binbin Wang ◽  
Ke Zhang ◽  
Awadalkareem Adam ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Airway Epithelial Cells ◽  
Host Responses ◽  
Airway Epithelial ◽  
Global Public Health ◽  
Significant Difference ◽  
Non Coding Rnas ◽  
Almost All

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5'-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS41 CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3'-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

scholarly journals SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Youwei Zhu ◽  
Zhaoyang Zhang ◽  
Jia Song ◽  
Weizhou Qian ◽  
Xiangqian Gu ◽  
...  
Keyword(s):  
Differential Expression ◽  
Molecular Mechanisms ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Health Crisis ◽  
Host Interactions ◽  
Interferon Pathway ◽  
Host Innate Immune Response ◽  
Susceptible Gene

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.

scholarly journals Network-based Virus-Host Interaction Prediction with Application to SARS-CoV-2

2020 ◽  
Author(s):  
Hangyu Du ◽  
Feng Chen ◽  
Hongfu Liu ◽  
Pengyu Hong
Keyword(s):  
Molecular Mechanisms ◽  
Interaction Network ◽  
Spectrum Prediction ◽  
Health Crisis ◽  
Host Interactions ◽  
Multi Scale ◽  
Host Interaction ◽  
Human Proteins ◽  
Potential Risks ◽  
Insight Into

COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has quickly become a global health crisis since the first report of infection in December of 2019. However, the infection spectrum of SARS-CoV-2 and its comprehensive protein-level interactions with hosts remain unclear. There is a massive amount of under-utilized data and knowledge about RNA viruses highly relevant to SARS-CoV-2 and their hosts’ proteins. More in-depth and more comprehensive analyses of that knowledge and data can shed new insight into the molecular mechanisms underlying the COVID-19 pandemic and reveal potential risks. In this work, we constructed a multi-layer virus-host interaction network to incorporate these data and knowledge. A machine learning-based method, termed Infection Mechanism and Spectrum Prediction (IMSP), was developed to predict virus-host interactions at both protein and organism levels. Our approach revealed five potential infection targets of SARS-CoV-2, which deserved public health attention, and eight highly possible interactions between SARS-CoV-2 proteins and human proteins. Given a new virus, IMSP can utilize existing knowledge and data about other highly relevant viruses to predict multi-scale interactions between the new virus and potential hosts.

scholarly journals Characterization of methylation signatures in spontaneous preterm birth

2021 ◽  
Author(s):  
Heather M Brockway ◽  
Samantha L Wilson ◽  
Suhas G Kallapur ◽  
Catalin S Buhimschi ◽  
Louis J Muglia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preterm Birth ◽  
Molecular Mechanisms ◽  
Methylation Pattern ◽  
Global Public Health ◽  
Spontaneous Preterm Birth ◽  
Placental Development ◽  
Health Crisis ◽  
Histologic Chorioamnionitis ◽  
And Function

AbstractPreterm birth (PTB) is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous PTB (isPTB) and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology, and our transcriptomics studies suggest a role for placental maturity in isPTB. It is known that placental methylation changes over gestation and we hypothesized that if placental hypermaturity is present in our samples, we would observe unique isPTB methylation signature as well as identify loci where isPTB methylation is more similar to that of term birth (TB) than the gestational age matched controls. Our results indicate the isPTB DNA methylation pattern mimics the TB methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions (DMRs) fitting the isPTB specific hypomethylation (relative to the controls) pattern were identified, indicating unusually high similarity in DNA methylation between isPTB and TB samples. In contrast, 1,718 acute histologic chorioamnionitis(AHC) specific DMRs were identified with hypermethylated DMRs in WNT and cadherin pathways when compared to isPTB and TB samples. In these AHC DMRs, there were no significant differences between the isPTB and TB, which indicated again, a striking level of similarly between isPTB and TB sample sets. Taken together, these data reflect a more mature placenta than expected which may be impacting birth timing.

scholarly journals TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections

2021 ◽  
Vol 118 (14) ◽  
pp. e2100225118
Author(s):  
Seoyun Yum ◽  
Minghao Li ◽  
Yan Fang ◽  
Zhijian J. Chen
Keyword(s):  
Viral Infections ◽  
Adenosine Monophosphate ◽  
Nuclear Factor Κb ◽  
Cyclic Guanosine Monophosphate ◽  
Immune Defense ◽  
Guanosine Monophosphate ◽  
Type I Interferons ◽  
Type I ◽  
Autophagy Induction ◽  
Independent Functions

The induction of type I interferons through the transcription factor interferon regulatory factor 3 (IRF3) is considered a major outcome of stimulator of interferon genes (STING) activation that drives immune responses against DNA viruses and tumors. However, STING activation can also trigger other downstream pathways such as nuclear factor κB (NF-κB) signaling and autophagy, and the roles of interferon (IFN)-independent functions of STING in infectious diseases or cancer are not well understood. Here, we generated a STING mouse strain with a mutation (S365A) that disrupts IRF3 binding and therefore type I interferon induction but not NF-κB activation or autophagy induction. We also generated STING mice with mutations that disrupt the recruitment of TANK-binding kinase 1 (TBK1), which is important for both IRF3 and NF-κB activation but not autophagy induction (L373A or ∆CTT, which lacks the C-terminal tail). The STING-S365A mutant mice, but not L373A or ∆CTT mice, were still resistant to herpes simplex virus 1 (HSV-1) infections and mounted an antitumor response after cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) treatment despite the absence of STING-induced interferons. These results demonstrate that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.

Preparation and Antitubercular Activities of Palindromic Hydrazinecarbothioamides and Carbonothioic Dihydrazides

2019 ◽  
Vol 16 (11) ◽  
pp. 1202-1210 ◽  
Author(s):  
Michael Joseps Hearn ◽  
Gwendolyn Towers ◽  
Michael Henry Cynamon
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Virulent Strain ◽  
Chemotherapeutic Agents ◽  
Disc Diffusion ◽  
Global Public Health ◽  
Health Crisis ◽  
Chemical Structures ◽  
Public Health Crisis ◽  
Zones Of Inhibition ◽  
Diffusion Assay

Background:With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, prompting research into new classes of compounds, as well as the re-evaluation of known chemotherapeutic agents.Objectives:The antimycobacterial activities associated with some recently-reported thiocarbonyl compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug design and discovery.Methods:In the present study, the title compounds 3 and 4 were prepared by the condensation of hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc diffusion, and minimum inhibitory concentrations were determined against the virulent strain M. tuberculosis Erdman.Results:The chemical structures of these thermally stable compounds were determined by IR, 1HNMR, 13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates. Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound 3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 µg/mL.Conclusion:We found that the title compounds may be prepared conveniently in excellent purity and good yields. They are readily identified on the basis of their characteristic spectra. Some members of this class showed significant activities against mycobacteria. We conclude that further work will be warranted in exploring the antitubercular properties of these compounds.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

2019 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Mahsa Hatami ◽  
Mina Abdolahi ◽  
Neda Soveyd ◽  
Mahmoud Djalali ◽  
Mansoureh Togha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
English Language ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Nuclear Factor Κb ◽  
General Term ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Polymeric Nanoparticles ◽  
Volume Ratio ◽  
Fold Increase ◽  
Multi Drug Resistance ◽  
Health Crisis ◽  
Pharmaceutical Properties ◽  
Simplex Virus ◽  
The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

Impact of Novel Coronavirus (COVID-19) on Pregnant Women: A Review

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Saima Habeeb ◽  
Manju Chugani
Keyword(s):  
Pregnant Women ◽  
Vertical Transmission ◽  
Respiratory Infections ◽  
Age Groups ◽  
Well Being ◽  
Fetal Outcome ◽  
Global Public Health ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
The Impact

: The novel coronavirus infection (COVID‐19) is a global public health emergency.Since its outbreak in Wuhan, China in December 2019, the infection has spread at an alarming rate across the globe and humans have been locked down to their countries, cities and homes. As of now, the virus has affected over 20million people globally and has inflicted over 7 lac deaths. Nevertheless, the recovery rate is improving with each passing day and over 14 million people have recuperated so far. The statistics indicate that nobody is immune to the disease as the virus continues to spread among all age groups; newborns to the elders, and all compartmentsincluding pregnant women. However, pregnant women may be more susceptible to this infection as they are, in general, highly vulnerable to respiratory infections. There is no evidence for vertical transmission of the COVID-19 virus among pregnant women, but an increased prevalence of preterm deliveries. Besides this, the COVID-19 may alter immune response at the maternal-fetal interface and affect the well-being of mothers as well as infants. Unfortunately, there is limited evidence available in the open literature regarding coronavirus infection during pregnancy and it now appears that certain pregnant women have infected during the present 2019-nCoV pandemic. In this short communication, we study the impact of the COVID-19 infection on vertical transmission and fetal outcome among pregnant women.

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