scholarly journals NAD+ Degrading Enzymes, Evidence for Roles During Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Arnold Tan ◽  
Craig L. Doig
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Nicotinamide Adenine Dinucleotide ◽  
Metabolic Dysfunction ◽  
Enzymatic Cleavage ◽  
Post Translational Modifications ◽  
Substrate Proteins ◽  
Hydrolysis Of ◽  
Response Activation ◽  
Pathogenic Infection

Declines in cellular nicotinamide adenine dinucleotide (NAD) contribute to metabolic dysfunction, increase susceptibility to disease, and occur as a result of pathogenic infection. The enzymatic cleavage of NAD+ transfers ADP-ribose (ADPr) to substrate proteins generating mono-ADP-ribose (MAR), poly-ADP-ribose (PAR) or O-acetyl-ADP-ribose (OAADPr). These important post-translational modifications have roles in both immune response activation and the advancement of infection. In particular, emergent data show viral infection stimulates activation of poly (ADP-ribose) polymerase (PARP) mediated NAD+ depletion and stimulates hydrolysis of existing ADP-ribosylation modifications. These studies are important for us to better understand the value of NAD+ maintenance upon the biology of infection. This review focuses specifically upon the NAD+ utilising enzymes, discusses existing knowledge surrounding their roles in infection, their NAD+ depletion capability and their influence within pathogenic infection.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

scholarly journals The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Julie M. Steinbrink ◽  
Rachel A. Myers ◽  
Kaiyuan Hua ◽  
Melissa D. Johnson ◽  
Jessica L. Seidelman ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacterial Infection ◽  
Viral Infection ◽  
Fungal Infection ◽  
Host Response ◽  
Hospitalized Patients ◽  
Neutrophil Activation ◽  
Heme Biosynthesis ◽  
Transcriptional Analysis ◽  
Diagnostic Approaches

Abstract Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. Methods In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. Results Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). Conclusions Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

Do fish erythrocytes have a potential role in the immune response orchestration after viral infection and DNA vaccination

2013 ◽  
Vol 34 (6) ◽  
pp. 1669-1670
Author(s):  
M. Ortega-Villaizan ◽  
A. Martínez-López ◽  
P. García-Valtanen ◽  
A.H. Teruel ◽  
L. Perez ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Potential Role ◽  
Dna Vaccination

scholarly journals Epigenetic Changes in the Regulation of Nicotiana tabacum Response to Cucumber Mosaic Virus Infection and Symptom Recovery through Single-Base Resolution Methylomes

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 402 ◽  
Author(s):  
Chenguang Wang ◽  
Chaonan Wang ◽  
Wenjie Xu ◽  
Jingze Zou ◽  
Yanhong Qiu ◽  
...  
Keyword(s):  
Immune Response ◽  
Nicotiana Tabacum ◽  
Viral Infection ◽  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Developmental Stages ◽  
Reduced Representation ◽  
Reduced Representation Bisulfite Sequencing ◽  
Symptom Recovery

Plants have evolved multiple mechanisms to respond to viral infection. These responses have been studied in detail at the level of host immune response and antiviral RNA silencing (RNAi). However, the possibility of epigenetic reprogramming has not been thoroughly investigated. Here, we identified the role of DNA methylation during viral infection and performed reduced representation bisulfite sequencing (RRBS) on tissues of Cucumber mosaic virus (CMV)-infected Nicotiana tabacum at various developmental stages. Differential methylated regions are enriched with CHH sequence contexts, 80% of which are located on the gene body to regulate gene expression in a temporal style. The methylated genes depressed by methyltransferase inhibition largely overlapped with methylated genes in response to viral invasion. Activation in the argonaute protein and depression in methyl donor synthase revealed the important role of dynamic methylation changes in modulating viral clearance and resistance signaling. Methylation-expression relationships were found to be required for the immune response and cellular components are necessary for the proper defense response to infection and symptom recovery.

scholarly journals Tumour viruses and innate immunity

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160267 ◽  
Author(s):  
Sharon E. Hopcraft ◽  
Blossom Damania
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Host Cells ◽  
Oncogenic Viruses ◽  
Barr Virus ◽  
Human T Cell ◽  
Epstein Barr

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system. This article is part of the themed issue ‘Human oncogenic viruses’.

scholarly journals Comparison of Type I Interferon Expression in Adult and Neonatal Mice during Respiratory Viral Infection

10.29007/ltkw ◽  
2019 ◽  
Author(s):  
Zifeng Liang
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Mouse Models ◽  
Post Infection ◽  
Type I Interferon ◽  
Sendai Virus ◽  
Killer Cell ◽  
Type I ◽  
Respiratory Viral Infection ◽  
Neonatal Mice

The aim of this paper is to identify the difference of type I interferon expression in 2- day neonatal and six-to-eight-weeks adult mice infected by Sendai virus (SeV), a single- stranded RNA virus of the family Paramyxoviridae. Sendai virus mimics the influence of respiratory syncytial virus (RSV) on humans, but does not infect humans. Although RSV has a fatal impact on people across age groups, little is understood about this common virus and the disparity between neonatal and adult immune response to it. It has been suggested by past findings that Type I interferon mRNA is present in higher levels in adults than in neonates, however there is a greater amount of interferon proteins in neonates rather than adults. To test the hypothesis that neonates are more capable of interferon production and preventing the translation of viral protein, I observed mouse models of respiratory viral infection and determined the expression of IFN-α1, IFN-α2, IFN-α5, IFN-α6, IFN-α7, IFN-β in archived mouse lung tissue samples harvested on different days post-infection with quantitative real time PCR. Expression of Glyceraldehyde 3-phosphate dehydrogenase(GAPDH), a housekeeping gene expressed constitutively in all mouse models, was used as a positive control of the experiment. To determine the ideal concentration of primer used in qPCR, primer reconstitution, primer optimization, and gel electrophoresis were conducted in advance. In addition, technical replicates and biological replicates were used to reduce error and confirm results in qPCR. In accordance with previous discovery, I found an upward trend in adults’ interferon expression from post-infection day 1 to day 5, and levels off in day 7. In contrast, neonatal levels were much higher on day 1 and remained high over the course of infection. This explains how type I interferon expression is altered in neonates to help them clear the virus at the same efficiency as adults without causing inflammation. Future research on immune response differences in human infection should focus on the evaluation of interferon protein amounts, as well as the analysis of activation of molecules downstream of the type I interferon receptors, such as signal transducer and activator of transcription (STAT) protein family. It is also crucial to compare immune cells like macrophages and natural killer cell activity in adult and neonatal mice during viral infection.

scholarly journals Multiplexed Detection of COVID-19 with Single-Molecule Technology

2021 ◽  
Author(s):  
Noa Furth ◽  
Shay Shilo ◽  
Niv Cohen ◽  
Nir Erez ◽  
Vadim Fedyuk ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Single Molecule ◽  
Direct Detection ◽  
Genetic Material ◽  
Diagnostic Tools ◽  
Proof Of Concept ◽  
Multiplexed Detection ◽  
Diagnostic Approaches ◽  
Quantitative Nature

The COVID-19 pandemic raises the need for diverse diagnostic approaches to rapidly detect different stages of viral infection. The flexible and quantitative nature of single-molecule imaging technology renders it optimal for development of new diagnostic tools. Here we present a proof-of-concept for a single-molecule based, enzyme-free assay for multiplexed detection of SARS-CoV-2. The unified platform we developed allows direct detection of the viral genetic material from patients' samples, as well as their immune response consisting of IgG and IgM antibodies. Thus, it establishes a platform for diagnostics of COVID-19, which could also be adjusted to diagnose additional pathogens.

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