The Landscape of Human Proteins Interacting with Viruses and Other Pathogens (original) (raw)
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Comprehensive host-pathogen protein-protein interaction network analysis
BMC Bioinformatics, 2020
Background Infectious diseases are a cruel assassin with millions of victims around the world each year. Understanding infectious mechanism of viruses is indispensable for their inhibition. One of the best ways of unveiling this mechanism is to investigate the host-pathogen protein-protein interaction network. In this paper we try to disclose many properties of this network. We focus on human as host and integrate experimentally 32,859 interaction between human proteins and virus proteins from several databases. We investigate different properties of human proteins targeted by virus proteins and find that most of them have a considerable high centrality scores in human intra protein-protein interaction network. Investigating human proteins network properties which are targeted by different virus proteins can help us to design multipurpose drugs. Results As host-pathogen protein-protein interaction network is a bipartite network and centrality measures for this type of networks are s...
Methods in molecular biology (Clifton, N.J.), 2012
Using global approaches and high-throughput technologies in virology brings a new vision of the infections physiology and allows the identification of cellular factors, mandatory for viral life cycle, that could be targeted by original therapeutic agents. It opens perspectives for the treatment of viral infections by acting on cellular pathways that the virus must use for its own replication. Combining these new molecules with classical antiviral drugs and immunomodulators diversifies and enlarges the antiviral arsenal and contributes to fight drug resistance. Our laboratory and others are constructing virus-human interactomes to propose a comprehensive analysis of viral infection at the cellular level. Studying these infection maps, where the viral infection can be visualized as perturbation of the human protein-protein interaction network, and identifying the biological functions that are impaired by these perturbations may lead to discovery of new therapeutic targets. These virus...
VirusMINT: a viral protein interaction database
Nucleic Acids Research, 2009
Understanding the consequences on host physiology induced by viral infection requires complete understanding of the perturbations caused by virus proteins on the cellular protein interaction network. The VirusMINT database (http://mint.bio.uniroma2\. it/virusmint/) aims at collecting all protein interactions between viral and human proteins reported in the literature. VirusMINT currently stores over 5000 interactions involving more than 490 unique viral proteins from more than 110 different viral strains. The whole data set can be easily queried through the search pages and the results can be displayed with a graphical viewer. The curation effort has focused on manuscripts reporting interactions between human proteins and proteins encoded by some of the most medically relevant viruses: papilloma viruses, human immunodeficiency virus 1, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, herpes viruses and Simian virus 40.
Host-pathogen protein interactions predicted by comparative modeling
Protein Science, 2007
Pathogens have evolved numerous strategies to infect their hosts, while hosts have evolved immune responses and other defenses to these foreign challenges. The vast majority of host-pathogen interactions involve protein-protein recognition, yet our current understanding of these interactions is limited. Here, we present and apply a computational whole-genome protocol that generates testable predictions of host-pathogen protein interactions. The protocol first scans the host and pathogen genomes for proteins with similarity to known protein complexes, then assesses these putative interactions, using structure if available, and, finally, filters the remaining interactions using biological context, such as the stage-specific expression of pathogen proteins and tissue expression of host proteins. The technique was applied to 10 pathogens, including species of Mycobacterium, apicomplexa, and kinetoplastida, responsible for ''neglected'' human diseases. The method was assessed by (1) comparison to a set of known host-pathogen interactions, (2) comparison to gene expression and essentiality data describing host and pathogen genes involved in infection, and (3) analysis of the functional properties of the human proteins predicted to interact with pathogen proteins, demonstrating an enrichment for functionally relevant host-pathogen interactions. We present several specific predictions that warrant experimental follow-up, including interactions from previously characterized mechanisms, such as cytoadhesion and protease inhibition, as well as suspected interactions in hypothesized networks, such as apoptotic pathways. Our computational method provides a means to mine whole-genome data and is complementary to experimental efforts in elucidating networks of host-pathogen protein interactions.
Nucleic Acids Research, 2009
Infectious diseases caused by viral agents kill millions of people every year. The improvement of prevention and treatment of viral infections and their associated diseases remains one of the main public health challenges. Towards this goal, deciphering virus-host molecular interactions opens new perspectives to understand the biology of infection and for the design of new antiviral strategies. Indeed, modelling of an infection network between viral and cellular proteins will provide a conceptual and analytic framework to efficiently formulate new biological hypothesis at the proteome scale and to rationalize drug discovery. Therefore, we present the first release of VirHostNet (Virus-Host Network), a public knowledge base specialized in the management and analysis of integrated virus-virus, virushost and host-host interaction networks coupled to their functional annotations. VirHostNet integrates an extensive and original literature-curated dataset of virus-virus and virus-host interactions (2671 nonredundant interactions) representing more than 180 distinct viral species and one of the largest human interactome (10 672 proteins and 68 252 nonredundant interactions) reconstructed from publicly available data. The VirHostNet Web interface provides appropriate tools that allow efficient query and visualization of this infected cellular network. Public access to the VirHostNet knowledge-based system is available at
Global approaches to study protein–protein interactions among viruses and hosts
Future microbiology, 2010
While high-throughput protein-protein interaction screens were first published approximately 10 years ago, systematic attempts to map interactions among viruses and hosts started only a few years ago. HIV-human interactions dominate host-pathogen interaction databases (with approximately 2000 interactions) despite the fact that probably none of these interactions have been identified in systematic interaction screens. Recently, combinations of protein interaction data with RNAi and other functional genomics data allowed researchers to model more complex interaction networks. The rapid progress in this area promises a flood of new data in the near future, with clinical applications as soon as structural and functional genomics catches up with next-generation sequencing of human variation and structure-based drug design.
An Integrated Map of HIV-Human Protein Complexes that Facilitate Viral Infection
PLoS ONE, 2014
Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection. Based on our approach we identified a global map of 40 HIV-human protein complexes with putative roles in HIV infection, some of which are involved in DNA replication and repair, transcription, translation, and cytoskeletal regulation. Targeted RNAi screens were used to validate several proteins and complexes for functional impact on viral infection. Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.
2020
Background Influenza A virus (IAV) infection is a serious public health problem not only in South East Asia but also in European and African countries. Scientists are using network biology to dig deep into the essential host factors responsible for regulation of virus infections. Researchers can explore the virus invasion into the host cells by studying the virus-host relationship based on their protein-protein interaction network. Methods In this study, we present a comprehensive IAV-host protein-protein interaction network that is obtained based on the literature-curated protein interaction datasets and some important interaction databases. The network is constructed in Cytoscape and analyzed with its plugins including CytoHubba, CytoCluster, MCODE, ClusterViz and ClusterOne. In addition, Gene Ontology and KEGG enrichment analyses are performed on the highly IAV-associated human proteins. We also compare the current results with those from our previous study on Hepatitis C Virus (...
Prediction of host-pathogen protein interactions by extended network model
TURKISH JOURNAL OF BIOLOGY, 2021
Introduction Infectious diseases, such as HIV, Influenza, SARS, and COVID-19 are caused by viral and bacterial infections and affect the health of millions of people, and even lead to deaths each year. For example, infectious diseases resulted in 9.2 million deaths in 2013, accounting for about 17% of all deaths (Naghavi et al., 2015). In addition to affecting human health, it results in major economic losses. New coronavirus disease (COVID-19) has spread to many countries and is declared as a pandemic by the World Health Organization. According to OECD studies, the world economy is expected to contract by at least 2.4% in 2020 1. According to UNCTAD, by the end of 2020, foreigndirect investment flowsare expected to decrease by 30%-40% 2. ILO foresees that COVID-19 pandemic could 1 Organisation for Economic Cooperation and Development (OECD) (2020). OECD Interim Economic Assessment Coronavirus: the world economy at risk [online]. Website https://www.oecd.org/berlin/ publikationen/Interim-Economic-Assessment-2-March-2020.pdf [accessed 02 March 2020]. 2 United Nations Conference on Tradeand Development (UNCTAD) (2020). Impact of the COVID-19 Pandemic on Global FDI and GVCs-increase global unemployment by almost 25 million by 2020 3. One key characteristic of infectious diseases is that the proteins of the pathogen organism interact withthe host organism's proteins and influence their functionality. Understanding the mechanism that governs such interactions between the host and pathogenic organisms is of utmost importance in developing treatment strategies. Existing studies on protein interactions can be considered in two categories. The first one explores the interactions of proteins within a species (Mei, 2013). These studies model the collection of interactions as protein-protein interaction (PPI) networks. Such networks has already been successfully used to understand the functions of proteins and the biological processes controlling vital functions of the cell and the results have been published in Updated Analysis [online]. https://unctad.org/en/PublicationsLibrary/ diaeiainf2020d3_en.pdf [4 March 2020].