scholarly journals Structure of the 5' untranslated region in SARS-CoV-2 genome and its specific recognition by innate immune system via the human oligoadenylate synthase 1

2021 ◽  
Author(s):  
Emmanuelle Bignon ◽  
Tom Miclot ◽  
Alessio Terenzi ◽  
Giampaolo Barone ◽  
Antonio Monari
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Viral Infections ◽  
Interaction Network ◽  
High Sensitivity ◽  
Innate Immune ◽  
System Response ◽  
Oligoadenylate Synthetase ◽  
Stem Loop ◽  
Viral Maturation

The 2'-5'-oligoadenylate synthetase 1 (OAS1) have been identified as one of the key enzymes driving the innate immune system response to SARS-CoV-2 infection and has been related to COVID-19 severity. OAS1 is a sensor of endogenous RNA that triggers the 2'-5' oligoadenylate/RNase L pathway in response to viral infections, ultimately activating the RNA-Lyase which cleaves endogenous and exogenous RNA hence impeding the viral maturation. Upon SARS-CoV-2 infection, OAS1 is responsible for the recognition of viral RNA and has been shown to possess a particularly high sensitivity for the 5'-untranslated (5'-UTR) RNA region, which is organized in a double-strand stem loop motif (SL1). Yet the structure of the nucleic acid/protein complex has not been resolved. Here, we report the structure of the OAS1/SL1 complex generated by molecular modeling, including enhanced sampling approaches. We also pinpoint how SL1 region enhances the interaction network with the enzyme, promoting specific hydrogen bonds which are absent in normal double strand RNA fragments, hence rationalizing the high affinity shown by OAS1.

A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape

2019 ◽  
Vol 20 (4) ◽  
pp. 493-502 ◽  
Author(s):  
Philipp Hubel ◽  
Christian Urban ◽  
Valter Bergant ◽  
William M. Schneider ◽  
Barbara Knauer ◽  
...  
Keyword(s):  
Immune System ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Innate Immune System ◽  
Interaction Network ◽  
Innate Immune ◽  
Interferon Stimulated Genes

scholarly journals The innate immune system and neurogenesis as modulating mechanisms of electroconvulsive therapy in pre-clinical studies

2020 ◽  
Vol 34 (10) ◽  
pp. 1086-1097
Author(s):  
Juliette Giacobbe ◽  
Carmine M Pariante ◽  
Alessandra Borsini
Keyword(s):  
Cell Proliferation ◽  
Immune System ◽  
Electroconvulsive Therapy ◽  
Clinical Studies ◽  
Innate Immune System ◽  
Innate Immune ◽  
System Response ◽  
Treatment Resistant ◽  
The Impact ◽  
Over Time

Background: Electroconvulsive therapy (ECT) is a powerful and fast-acting anti-depressant strategy, often used in treatment-resistant patients. In turn, patients with treatment-resistant depression often present an increased inflammatory response. The impact of ECT on several pathophysiological mechanisms of depression has been investigated, with a focus which has largely been on cellular and synaptic plasticity. Although changes in the immune system are known to influence neurogenesis, these processes have principally been explored independently from each other in the context of ECT. Objective: The aim of this review was to compare the time-dependent consequences of acute and chronic ECT on concomitant innate immune system and neurogenesis-related outcomes measured in the central nervous system in pre-clinical studies. Results: During the few hours following acute electroconvulsive shock (ECS), the expression of the astrocytic reactivity marker glial fibrillary acidic protein (GFAP) and inflammatory genes, such as cyclooxygenase-2 (COX2), were significantly increased together with the neurogenic brain-derived neurotrophic factor (BDNF) and cell proliferation. Similarly, chronic ECS caused an initial upregulation of the same astrocytic marker, immune genes, and neurogenic factors. Interestingly, over time, inflammation appeared to be dampened, while glial activation and neurogenesis were maintained, after either acute or chronic ECS. Conclusion: Regardless of treatment duration ECS would seemingly trigger a rapid increase in inflammatory molecules, dampened over time, as well as a long-lasting activation of astrocytes and production of growth and neurotrophic factors, leading to cell proliferation. This suggests that both innate immune system response and neurogenesis might contribute to the efficacy of ECT.

scholarly journals Transcriptomic Analysis of Aedes aegypti Innate Immune System in Response to Ingestion of Chikungunya Virus

2019 ◽  
Vol 20 (13) ◽  
pp. 3133 ◽  
Author(s):  
Liming Zhao ◽  
Barry W. Alto ◽  
Yongxing Jiang ◽  
Fahong Yu ◽  
Yanping Zhang
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Aedes Aegypti ◽  
Innate Immune System ◽  
Chikungunya Virus ◽  
Innate Immune ◽  
Transcriptomic Analysis ◽  
System Response ◽  
Sequencing Analysis ◽  
Immune System Response

Aedes aegypti (L.) is the primary vector of emergent mosquito-borne viruses, including chikungunya, dengue, yellow fever, and Zika viruses. To understand how these viruses interact with their mosquito vectors, an analysis of the innate immune system response was conducted. The innate immune system is a conserved evolutionary defense strategy and is the dominant immune system response found in invertebrates and vertebrates, as well as plants. RNA-sequencing analysis was performed to compare target transcriptomes of two Florida Ae. aegypti strains in response to chikungunya virus infection. We analyzed a strain collected from a field population in Key West, Florida, and a laboratory strain originating from Orlando. A total of 1835 transcripts were significantly expressed at different levels between the two Florida strains of Ae. aegypti. Gene Ontology analysis placed these genes into 12 categories of biological processes, including 856 transcripts (up/down regulated) with more than 1.8-fold (p-adj (p-adjust value) ≤ 0.01). Transcriptomic analysis and q-PCR data indicated that the members of the AaeCECH genes are important for chikungunya infection response in Ae. aegypti. These immune-related enzymes that the chikungunya virus infection induces may inform molecular-based strategies for interruption of arbovirus transmission by mosquitoes.

scholarly journals Effects of Metal Oxide Nanoparticles on Toll-Like Receptor mRNAs in Human Monocytes

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 127 ◽  
Author(s):  
Vladislav A. Vasilichin ◽  
Sergey A. Tsymbal ◽  
Anna F. Fakhardo ◽  
Elizaveta I. Anastasova ◽  
Andrey S. Marchenko ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Metal Oxide Nanoparticles ◽  
Innate Immune ◽  
Future Research ◽  
System Response ◽  
Widespread Application ◽  
Host Immune Responses ◽  
Immune System Response ◽  
Fragmented Data

For the widespread application of nanotechnology in biomedicine, it is necessary to obtain information about their safety. A critical problem is presented by the host immune responses to nanomaterials. It is assumed that the innate immune system plays a crucial role in the interaction of nanomaterials with the host organism. However, there are only fragmented data on the activation of innate immune system factors, such as toll-like receptors (TLRs), by some nanoparticles (NPs). In this study, we investigated TLRs’ activation by clinically relevant and promising NPs, such as Fe3O4, TiO2, ZnO, CuO, Ag2O, and AlOOH. Cytotoxicity and effects on innate immunity factors were studied in THP-1(Tohoku Hospital Pediatrics-1) cell culture. NPs caused an increase of TLR-4 and -6 expression, which was comparable with the LPS-induced level. This suggests that the studied NPs can stimulate the innate immune system response inside the host. The data obtained should be taken into account in future research and to create safe-by-design biomedical nanomaterials.

The older brain, inflammation, vaccination and the prevention of dementia

2010 ◽  
Vol 20 (4) ◽  
pp. 288-308
Author(s):  
JW Neal
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Transgenic Animal ◽  
Innate Immune ◽  
Brain Inflammation ◽  
Amyloid Peptide ◽  
System Response ◽  
Protective Function

SummaryAn important protective function of the brain's innate immune system is to detect the presence of proteins such as amyloid and to remove them before they become neurotoxic, as is thought to occur in Alzheimer's disease (AD). Ageing affects the immune system response to infection and can influence the systemic response to vaccination and other potential immunotherapeutic agents. The generation of systemic antibodies is a vital component of the immune response, facilitating the identification and clearance of pathogens from the central nervous system (CNS). Experimental evidence using transgenic animal models of AD has shown successful clearance of amyloid from the CNS following vaccination with an amyloid peptide, and consequently a trial of amyloid beta peptide (Aβ) vaccination was undertaken in older people with AD. This produced some unexpected results, as not only was there evidence for amyloid plaque removal, but also a small number of cases developed encephalitis. A detailed review of the response to vaccination and the neuropathology findings are discussed, showing that the findings are understandable given the effects of ageing upon the innate immune system in the brain. Finally, the therapeutic potential of manipulating the regulatory components of the ageing innate immune system in order to inhibit brain inflammation and reduce cognitive decline is outlined.

scholarly journals Cytokine storm interference

2021 ◽  
Vol 4 (1) ◽  
pp. 185-187
Author(s):  
Michael John Dochniak
Keyword(s):  
Innate Immunity ◽  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Innate Immune System ◽  
Distress Syndrome ◽  
Viral Infections ◽  
Acute Infection ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Healthy Individuals

Viral infections are a natural and inevitable part of life. In healthy individuals, mortality increases when the body’s innate immune system quickly activates, creating a cytokine storm. A rapid and excessive release of cytokines into the bloodstream can cause acute respiratory distress syndrome and death. This communication proposes inhibiting cytokine storm development through forced atopy. Hyper-allergenic skin cream therapy stimulates adaptive immunity to support innate immunity before acute infection.

scholarly journals Innate immune responses in RNA viral infection

2020 ◽  
Author(s):  
Qian Xu ◽  
Yuting Tang ◽  
Gang Huang
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Viral Infection ◽  
Immune Cells ◽  
Innate Immune System ◽  
Viral Infections ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Past Century ◽  
Main Role

AbstractRNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

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