scholarly journals VPTMdb: a viral posttranslational modification database

2020 ◽  
Author(s):  
Yujia Xiang ◽  
Quan Zou ◽  
Lilin Zhao
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Drug Targets ◽  
Viral Infections ◽  
Interaction Analysis ◽  
Human Interaction ◽  
Host Cells ◽  
Phosphorylation Sites ◽  
Human Viruses ◽  
Disordered Regions

Abstract In viruses, posttranslational modifications (PTMs) are essential for their life cycle. Recognizing viral PTMs is very important for a better understanding of the mechanism of viral infections and finding potential drug targets. However, few studies have investigated the roles of viral PTMs in virus–human interactions using comprehensive viral PTM datasets. To fill this gap, we developed the first comprehensive viral posttranslational modification database (VPTMdb) for collecting systematic information of PTMs in human viruses and infected host cells. The VPTMdb contains 1240 unique viral PTM sites with 8 modification types from 43 viruses (818 experimentally verified PTM sites manually extracted from 150 publications and 422 PTMs extracted from SwissProt) as well as 13 650 infected cells’ PTMs extracted from seven global proteomics experiments in six human viruses. The investigation of viral PTM sequences motifs showed that most viral PTMs have the consensus motifs with human proteins in phosphorylation and five cellular kinase families phosphorylate more than 10 viral species. The analysis of protein disordered regions presented that more than 50% glycosylation sites of double-strand DNA viruses are in the disordered regions, whereas single-strand RNA and retroviruses prefer ordered regions. Domain–domain interaction analysis indicating potential roles of viral PTMs play in infections. The findings should make an important contribution to the field of virus–human interaction. Moreover, we created a novel sequence-based classifier named VPTMpre to help users predict viral protein phosphorylation sites. VPTMdb online web server (http://vptmdb.com:8787/VPTMdb/) was implemented for users to download viral PTM data and predict phosphorylation sites of interest.

scholarly journals Silencing Viral MicroRNA as a Novel Antiviral Therapy?

2009 ◽  
Vol 2009 ◽  
pp. 1-18 ◽  
Author(s):  
Ugo Moens
Keyword(s):  
Viral Particle ◽  
Viral Infections ◽  
Host Cells ◽  
Viral Diseases ◽  
Host Immune System ◽  
Intracellular Parasites ◽  
Viral Genes ◽  
Viral Microrna ◽  
Mirnas Expression ◽  
Human Viruses

Viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. Some viruses may also survive by transforming the infected cell into an immortal tumour cell. MicroRNAs are small non-coding transcripts that function as posttranscriptional regulators of gene expression. Viruses encode miRNAs that regulate expression of both cellular and viral genes, and contribute to the pathogenic properties of viruses. Hence, neutralizing the action of viral miRNAs expression by complementary single-stranded oligonucleotides or so-called anti-miRNAs may represent a strategy to combat viral infections and viral-induced pathogenesis. This review describes the miRNAs encoded by human viruses, and discusses the possible therapeutic applications of anti-miRNAs against viral diseases.

scholarly journals Bioinformatics analysis and collection of protein post-translational modification sites in human viruses

2020 ◽  
Author(s):  
Yujia Xiang ◽  
Quan Zou ◽  
Lilin Zhao
Keyword(s):  
Viral Protein ◽  
Protein Modification ◽  
Phosphorylation Site ◽  
Protein Domains ◽  
Human Interaction ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Human Proteins ◽  
Human Viruses

AbstractIn viruses, post-translational modifications (PTMs) are essential for their life cycle. Recognizing viral PTMs is very important for better understanding the mechanism of viral infections and finding potential drug targets. However, few studies have investigated the roles of viral PTMs in virus-human interactions using comprehensive viral PTM datasets. To fill this gap, firstly, we developed a viral post-translational modification database (VPTMdb) for collecting systematic information of viral PTM data. The VPTMdb contains 912 PTM sites that integrate 414 experimental-confirmed PTM sites with 98 proteins in 45 human viruses manually extracted from 162 publications and 498 PTMs extracted from UniProtKB/Swiss-Prot. Secondly, we investigated the viral PTM sequence motifs, the function of target human proteins, and characteristics of PTM protein domains. The results showed that (i) viral PTMs have the consensus motifs with human proteins in phosphorylation, SUMOylation and N-glycosylation. (ii) The function of human proteins that targeted by viral PTM proteins are related to protein targeting, translation, and localization. (iii) Viral PTMs are more likely to be enriched in protein domains. The findings should make an important contribution to the field of virus-human interaction. Moreover, we created a novel sequence-based classifier named VPTMpre to help users predict viral protein phosphorylation sites. Finally, an online web server was implemented for users to download viral protein PTM data and predict phosphorylation sites of interest.Author summaryPost-translational modifications (PTMs) plays an important role in the regulation of viral proteins; However, due to the limitation of data sets, there has been no detailed investigation of viral protein PTMs characteristics. In this manuscript, we collected experimentally verified viral protein post-translational modification sites and analysed viral PTMs data from a bioinformatics perspective. Besides, we constructed a novel feature-based machine learning model for predicting phosphorylation site. This is the first study to explore the roles of viral protein modification in virus infection using computational methods. The valuable viral protein PTM data resource will provide new insights into virus-host interaction.

scholarly journals Inter-proteomic posttranslational modifications of the SARS-CoV-2 and the host proteins ‒ A new frontier

2021 ◽  
pp. 153537022098678
Author(s):  
Suresh Mishra ◽  
Geetika Bassi ◽  
BL Grégoire Nyomba
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Cell Biology ◽  
Scientific Community ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Therapeutic Modality ◽  
Host Proteins

Posttranslational modification of proteins, which include both the enzymatic alterations of protein side chains and main-chain peptide bond connectivity, is a fundamental regulatory process that is crucial for almost every aspects of cell biology, including the virus-host cell interaction and the SARS-CoV-2 infection. The posttranslational modification of proteins has primarily been studied in cells and tissues in an intra-proteomic context (where both substrates and enzymes are part of the same species). However, the inter-proteomic posttranslational modifications of most of the SARS-CoV-2 proteins by the host enzymes and vice versa are largely unexplored in virus pathogenesis and in the host immune response. It is now known that the structural spike (S) protein of the SARS-CoV-2 undergoes proteolytic priming by the host serine proteases for entry into the host cells, and N- and O-glycosylation by the host cell enzymes during virion packaging, which enable the virus to spread. New evidence suggests that both SARS-CoV-2 and the host proteins undergo inter-proteomic posttranslational modifications, which play roles in virus pathogenesis and infection-induced immune response by hijacking the host cell signaling. The purpose of this minireview is to bring attention of the scientific community to recent cutting-edge discoveries in this understudied area. It is likely that a better insight into the molecular mechanisms involved may open new research directions, and thereby contribute to novel therapeutic modality development against the SARS-CoV-2. Here we briefly discuss the rationale and touch upon some unanswered questions in this context, especially those that require attention from the scientific community.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

The Role of Purinergic Signaling in Trichomonas vaginalis Infection

2020 ◽  
Vol 20 ◽  
Author(s):  
Micheli Ferla ◽  
Tiana Tasca
Keyword(s):  
Drug Targets ◽  
Trichomonas Vaginalis ◽  
Hiv Transmission ◽  
Cell Damage ◽  
Purinergic Signaling ◽  
Host Cells ◽  
Purine Nucleotides ◽  
Cellular Effects ◽  
Adverse Pregnancy ◽  
Purine Salvage Pathways

: Trichomoniasis, one of the most common non-viral sexually transmitted infections worldwide, is caused by the parasite Trichomonas vaginalis. The pathogen colonizes the human urogenital tract and the infection is associated with complications such as adverse pregnancy outcomes, cervical cancer, and an increase in HIV transmission. The mecha-nisms of pathogenicity are multifactorial, and controlling immune responses is essential for infection maintenance. Extra-cellular purine nucleotides are released by cells in physiological and pathological conditions, and they are hydrolyzed by enzymes called ecto-nucleotidases. The cellular effects of nucleotides and nucleosides occur via binding to purinoceptors, or throughthe uptake by nucleoside transporters. Altogether, enzymes, receptors and transporters constitute the purinergic signaling, a cellular network that regulates several effects in practically all systems including mammals, helminths, proto-zoa, bacteria, and fungi. In this context, this review updates the data on purinergic signaling involved in T. vaginalis biol-ogy and interaction with host cells, focusing on the characterization of ecto-nucleotidases and on purine salvage pathways. The implications of the final products, the nucleosides adenosine and guanosine, for human neutrophil response and vagi-nal epithelial cell damage reveal the purinergic signaling as a potential new mechanism for alternative drug targets.

Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration

2020 ◽  
Vol 16 ◽  
Author(s):  
Jogendra Singh Nim ◽  
Mohit Yadav ◽  
Lalit Kumar Gautam ◽  
Chaitali Ghosh ◽  
Shakti Sahi ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Functional Characterization ◽  
Host Cells ◽  
System Control ◽  
Xenorhabdus Nematophila ◽  
Functional Features ◽  
Dynamics Simulations ◽  
Species Specific ◽  
Rna Interaction

Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn-MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, XnMazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.

scholarly journals Targeting Viral Surface Proteins through Structure-Based Design

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1320
Author(s):  
Yogesh B Narkhede ◽  
Karen J Gonzalez ◽  
Eva-Maria Strauch
Keyword(s):  
Public Health ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Surface Proteins ◽  
Host Cells ◽  
Viral Fusion ◽  
Health It ◽  
Viral Particles ◽  
Pathogenic Viruses ◽  
Viral Surface

The emergence of novel viral infections of zoonotic origin and mutations of existing human pathogenic viruses represent a serious concern for public health. It warrants the establishment of better interventions and protective therapies to combat the virus and prevent its spread. Surface glycoproteins catalyzing the fusion of viral particles and host cells have proven to be an excellent target for antivirals as well as vaccines. This review focuses on recent advances for computational structure-based design of antivirals and vaccines targeting viral fusion machinery to control seasonal and emerging respiratory viruses.

The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity

2019 ◽  
Vol 400 (5) ◽  
pp. 629-638 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Measles Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Sequence Similarity ◽  
Eukaryotic Cell ◽  
Point Of View ◽  
Peptide Sequence ◽  
Human Viruses ◽  
Archaeal Ancestor ◽  
Borna Disease

Abstract Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Indeed, according to the viral eukaryogenesis hypothesis and in light of the endosymbiotic theory, the first eukaryotic cell (our lineage) originated as a consortium consisting of an archaeal ancestor of the eukaryotic cytoplasm, a bacterial ancestor of the mitochondria and a viral ancestor of the nucleus. From a pathologic point of view, the peptide sequence similarity between viruses and humans may provide a molecular platform for autoimmune crossreactions during immune responses following viral infections/immunizations.

scholarly journals The intracellular dynamic of protein palmitoylation

2010 ◽  
Vol 191 (7) ◽  
pp. 1229-1238 ◽  
Author(s):  
Christine Salaun ◽  
Jennifer Greaves ◽  
Luke H. Chamberlain
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Mammalian Cells ◽  
Protein Functionality ◽  
Peripheral Membrane Proteins ◽  
Protein Palmitoylation ◽  
Thioester Bond ◽  
Intracellular Sorting ◽  
Intracellular Dynamic ◽  
Insight Into

S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond. This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning. Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation. In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates. In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation.

scholarly journals The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses

2016 ◽  
Vol 90 (19) ◽  
pp. 8780-8794 ◽  
Author(s):  
Subhajit Poddar ◽  
Jennifer L. Hyde ◽  
Matthew J. Gorman ◽  
Michael Farzan ◽  
Michael S. Diamond
Keyword(s):  
Viral Infections ◽  
Transmembrane Protein ◽  
Flow Cytometric Analysis ◽  
Antiviral Effect ◽  
Host Cells ◽  
Type I ◽  
Targeted Gene Deletion ◽  
Multiple Organs ◽  
Viral Burden ◽  
Alphavirus Infection

ABSTRACTHost cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased inIfitm3−/−andIfitmlocus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,Ifitm3−/−mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested thatIfitm3−/−macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments withIfitm3−/−bone marrow-derived macrophages.Ifitm3−/−mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.IMPORTANCEThe interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion ofIfitm3as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

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