scholarly journals New Targets forZikaVirus Determined by Human-Viral Interactomic: A Bioinformatics Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Eduardo Esteves ◽  
Nuno Rosa ◽  
Maria José Correia ◽  
Joel P. Arrais ◽  
Marlene Barros
Keyword(s):  
Immune Response ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Zikv Infection ◽  
Antiviral Immune Response ◽  
Vesicular Traffic ◽  
Human Host ◽  
New Targets ◽  
Great Relevance

Identifying ZIKV factors interfering with human host pathways represents a major challenge in understanding ZIKV tropism and pathogenesis. The integration of proteomic, gene expression and Protein-Protein Interactions (PPIs) established between ZIKV and human host proteins predicted by the OralInt algorithm identified 1898 interactions with medium or high score (≥0.7). Targets implicated in vesicular traffic and docking were identified. New receptors involved in endocytosis pathways as ZIKV entry targets, using both clathrin-dependent (17 receptors) and independent (10 receptors) pathways, are described. New targets used by the ZIKV to undermine the host’s antiviral immune response are proposed based on predicted interactions established between the virus and host cell receptors and/or proteins with an effector or signaling role in the immune response such as IFN receptors and TLR. Complement and cytokines are proposed as extracellular potential interacting partners of the secreted form of NS1 ZIKV protein. Altogether, in this article, 18 new human targets for structural and nonstructural ZIKV proteins are proposed. These results are of great relevance for the understanding of viral pathogenesis and consequently the development of preventive (vaccines) and therapeutic targets for ZIKV infection management.

scholarly journals Systems Perspective of Morbillivirus Replication

2016 ◽  
Vol 26 (6) ◽  
pp. 389-400 ◽  
Author(s):  
Naveen Kumar ◽  
Sanjay Barua ◽  
Riyesh Thachamvally ◽  
Bhupendra Nath Tripathi
Keyword(s):  
Immune Response ◽  
Disease Resistance ◽  
Systems Biology ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Systems Perspective ◽  
Host Pathogen Interaction ◽  
Comprehensive Information

Systems biology refers to system-wide changes in biological components such as RNA/DNA (genomics), protein (proteomics) and lipids (lipidomics). In this review, we provide comprehensive information about morbillivirus replication. Besides discussing the role of individual viral/host proteins in virus replication, we also discuss how systems-level analyses could improve our understanding of morbillivirus replication, host-pathogen interaction, immune response and disease resistance. Finally, we discuss how viroinformatics is likely to provide important insights for understanding genome-genome, genome-protein and protein-protein interactions.

scholarly journals Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rommel J. Gestuveo ◽  
Jamie Royle ◽  
Claire L. Donald ◽  
Douglas J. Lamont ◽  
Edward C. Hutchinson ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Protein Interactions ◽  
Zika Virus ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Zikv Infection ◽  
Ubiquitin Protein Ligase ◽  
Mosquito Cells ◽  
Endoplasmic Reticulum Protein ◽  
Arboviral Diseases

AbstractThe escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop an Aedes aegypti cell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics. We identify 157 interactors and show that eight have potentially pro-viral activity during ZIKV infection in mosquito cells. Notably, silencing of transitional endoplasmic reticulum protein TER94 prevents ZIKV capsid degradation and significantly reduces viral replication. Similar results are observed if the TER94 ortholog (VCP) functioning is blocked with inhibitors in human cells. In addition, we show that an E3 ubiquitin-protein ligase, UBR5, mediates the interaction between TER94 and ZIKV capsid. Our study demonstrates a pro-viral function for TER94/VCP during ZIKV infection that is conserved between human and mosquito cells.

scholarly journals Bacteria Use Structural Imperfect Mimicry To Hijack The Host Interactome

2020 ◽  
Author(s):  
Natalia Sanchez de Groot ◽  
Marc Torrent Burgas
Keyword(s):  
Protein Interactions ◽  
Rational Design ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Eukaryotic Proteins ◽  
Host Pathogen ◽  
Imperfect Mimicry ◽  
The Way

ABSTRACTBacteria use protein-protein interactions to infect their hosts and hijack fundamental pathways, which ensures their survival and proliferation. Hence, the infectious capacity of the pathogen is closely related to its ability to interact with host proteins. Here, we show that hubs in the host-pathogen interactome are isolated in the pathogen network by adapting the geometry of the interacting interfaces. An imperfect mimicry of the eukaryotic interfaces allows pathogen proteins to actively bind to the host’s target while preventing deleterious effects on the pathogen interactome. Understanding how bacteria recognize eukaryotic proteins may pave the way for the rational design of new antibiotic molecules.

In silico specificity determination of neoantigen-reactive T-lymphocytes

2021 ◽  
Vol 67 (3) ◽  
pp. 251-258
Author(s):  
A.E. Kniga ◽  
I.V. Polyakov ◽  
A.V. Nemukhin
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Molecular Docking ◽  
Protein Interactions ◽  
Structural Features ◽  
Immune Recognition ◽  
Protein Protein Interactions ◽  
Binary Classifiers

Effective personalized immunotherapies of the future will need to capture not only the peculiarities of the patient’s tumor but also of his immune response to it. In this study, using results of in vitro high-throughput specificity assays, and combining comparative models of pMHCs and TCRs using molecular docking, we have constructed all-atom models for the putative complexes of all their possible pairwise TCR-pMHC combinations. For the models obtained we have calculated a dataset of physics-based scores and have trained binary classifiers that perform better compared to their solely sequence-based counterparts. These structure-based classifiers pinpoint the most prominent energetic terms and structural features characterizing the type of protein-protein interactions that underlies the immune recognition of tumors by T cells.

Prediction of Protein-Protein Interactions Between Human Host and Two Mycobacterial Organisms

2013 ◽  
pp. 175-187
Author(s):  
Oruganty Krishnadev ◽  
Shveta Bisht ◽  
Narayanaswamy Srinivasan
Keyword(s):  
Protein Interactions ◽  
Serine Proteases ◽  
Cellular Membrane ◽  
Human Pathogens ◽  
Protein Protein Interactions ◽  
Human Host ◽  
Interaction Partners ◽  
Human Proteins ◽  
Mycobacterial Antigens ◽  
Ras Signalling

The genomes of many human pathogens have been sequenced but the protein-protein interactions across a pathogen and human are still poorly understood. The authors apply a simple homology-based method to predict protein-protein interactions between human host and two mycobacterial organisms viz., M.tuberculosis and M.leprae. They focused on secreted proteins of pathogens and cellular membrane proteins to restrict to uncovering biologically significant and feasible interactions. Predicted interactions include five mycobacterial proteins of yet unknown function, thus suggesting a role for these proteins in pathogenesis. The authors predict interaction partners for secreted mycobacterial antigens such as MPT70, serine proteases and other proteins interacting with human proteins, such as toll-like receptors, ras signalling proteins and immune maintenance proteins, that are implicated in pathogenesis. These results suggest that the list of predicted interactions is suitable for further analysis and forms a useful step in the understanding of pathogenesis of these mycobacterial organisms.

scholarly journals Detection of the Potyviral Genome-Linked Protein VPg in Virions and Its Phosphorylation by Host Kinases

2002 ◽  
Vol 76 (24) ◽  
pp. 12703-12711 ◽  
Author(s):  
Pietri Puustinen ◽  
Minna-Liisa Rajamäki ◽  
Konstantin I. Ivanov ◽  
Jari P. T. Valkonen ◽  
Kristiina Mäkinen
Keyword(s):  
Protein Interactions ◽  
Kinase Activity ◽  
Systemic Infection ◽  
Proximal Part ◽  
Infection Cycle ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Solanum Commersonii ◽  
Wild Potato Species ◽  
Potato Virus A

ABSTRACT The multifunctional genome-linked protein (VPg) of Potato virus A (PVA; genus Potyvirus) was found to be phosphorylated as a part of the virus particle by a cellular kinase activity from tobacco. Immunoprecipitation, immunolabeling, and immunoelectron microscopy experiments showed that VPg is exposed at one end of the virion and it is accessible to protein-protein interactions. Substitution Ser185Leu at the C-proximal part of VPg reduces accumulation of PVA in inoculated leaves of the wild potato species Solanum commersonii and delays systemic infection, which is not observed in tobacco plants. Our data show that kinases of S. commersonii differentially recognize the VPg containing Ser or Leu at position 185, whereas both forms of VPg are similarly recognized by tobacco kinases. Taken together, our data imply that the virion-bound VPg may interact with host proteins and that phosphorylation of VPg may play a role in the VPg-mediated functions during the infection cycle of potyviruses.

scholarly journals A comprehensive library of fluorescent constructs of SARS-CoV-2 proteins and their initial characterization in different cell types

2020 ◽  
Author(s):  
Stéphanie Miserey-Lenkei ◽  
Katarina Trajkovic ◽  
Juan Martìn D'Ambrosio ◽  
Amanda J Patel ◽  
Alenka Čopič ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Fluorescent Proteins ◽  
Imaging Techniques ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Red Fluorescent Proteins ◽  
Late Endosomes ◽  
Initial Characterization ◽  
Different Cell Types

Comprehensive libraries of plasmids for SARS-CoV-2 proteins with various tags (e.g. Strep, HA, Turbo) are now available. They enable the identification of numerous potential protein-protein interactions between the SARS-CoV-2 virus and host proteins. To facilitate further cellular investigations, notably by imaging techniques, we present here a large library of SARS CoV-2 protein constructs fused with green and red fluorescent proteins and their initial characterization in various human cell lines including lung epithelial cell models (A549, BEAS-2B), as well as in budding yeast. The localization of a few SARS-CoV-2 proteins matches their proposed interactions with host proteins. These include the localization of Nsp13 to the centrosome, Orf3a to late endosomes, and Orf9b to mitochondria.

scholarly journals Integrative proteomics reveals exceptional diversity and versatility of mammalian humoral immunity

2020 ◽  
Author(s):  
Yufei Xiang ◽  
Zhe Sang ◽  
Lirane Bitton ◽  
Jianquan Xu ◽  
Yang Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Interactions ◽  
Specific Antigen ◽  
Cellular Protein ◽  
Protein Protein Interactions ◽  
Humoral Immune ◽  
High Affinity ◽  
Interaction Interface ◽  
Systematic Understanding ◽  
Antigen Antibody

SummaryThe humoral immune response is essential for the survival of mammals. However, we still lack a systematic understanding of the specific serologic antibody repertoire in response to an antigen. We developed a proteomic strategy to survey, at an unprecedented scale, the landscapes of antigen-engaged, serum-circulating repertoires of camelid heavy-chain antibodies (hcAbs). The sensitivity and robustness of this technology were validated using three antigens spanning orders of magnitude in immune response; thousands of divergent, high-affinity hcAb families were confidently identified and quantified. Using high-throughput structural modeling, cross-linking mass spectrometry, mutagenesis, and deep learning, we mapped and analyzed the epitopes of > 100,000 antigen-antibody complexes. Our results revealed a surprising diversity of high-affinity hcAbs for specific antigen binding on a variety of dominant epitopes. hcAbs perfect both shape and charge complementarity to target challenging antigens specifically; they can rapidly evolve to recognize a conserved, promiscuous cellular protein interaction interface, unraveling the convergent force that drives protein-protein interactions.

scholarly journals ADAR1 limits stress granule formation through both translation-dependent and translation-independent mechanisms

2021 ◽  
Author(s):  
Giulia A. Corbet ◽  
James M. Burke ◽  
Roy Parker
Keyword(s):  
Immune Response ◽  
Stress Response ◽  
Protein Interactions ◽  
Binding Activity ◽  
Innate Immune ◽  
Protein Protein Interactions ◽  
Granule Formation ◽  
Translation Inhibition ◽  
Translation Repression ◽  
Dsrna Binding

Stress granules (SGs) are cytoplasmic assemblies of RNA and protein that form when translation is repressed during the integrated stress response (ISR). SGs assemble from the combination of RNA-RNA, RNA-protein, and protein-protein interactions between mRNPs. The protein Adenosine deaminase acting on RNA 1 (ADAR1) recognizes and modifies dsRNAs within cells to prevent an aberrant innate immune response. ADAR1 localizes to SGs, and since RNA-RNA interactions contribute to SG assembly and dsRNA induces SGs, we examined how ADAR1 affects SG formation. First, we demonstrate that ADAR1 depletion triggers SGs by allowing endogenous dsRNA to activate the ISR through PKR activation and translation repression. However, we also show that ADAR1 limits SG formation independently of translation inhibition. ADAR1 repression of SGs is independent of deaminase activity, but dependent on dsRNA-binding activity, suggesting a model where ADAR1 binding limits RNA-RNA and/or RNA-protein interactions necessary for recruitment to SGs. Given that ADAR1 expression is induced during viral infection, these findings have implications for ADAR1's role in the antiviral response.

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