PIG—the pathogen interaction gateway

Protein–protein interactions (PPIs) play a vital role in initiating infection in a number of pathogens. Identifying which interactions allow a pathogen to infect its host can help us to understand methods of pathogenesis and provide potential targets for therapeutics. Public resources for studying host–pathogen systems, in particular PPIs, are scarce. To facilitate the study of host–pathogen PPIs, we have collected and integrated host–pathogen PPI (HP–PPI) data from a number of public resources to create the Pathogen Interaction Gateway (PIG). PIG provides a text based search and a BLAST interface for searching the HP–PPI data. Each entry in PIG includes information such as the functional annotations and the domains present in the interacting proteins. PIG provides links to external databases to allow for easy navigation among the various websites. Additionally, PIG includes a tool for visualizing a single HP–PPI network or two HP–PPI networks. PIG can be accessed at http://pig.vbi.vt.edu

The origin and prevention of pandemics.

Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change, and communication strategies. Because there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives

PATRIC, the bacterial bioinformatics database and analysis resource

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issu

HPIDB - a unified resource for host-pathogen interactions

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions (PPIs) play a crucial role in initiating infection in a host-pathogen system. Identification of these PPIs is important for understanding the underlying biological mechanism of infection and identifying putative drug targets. Database resources for studying host-pathogen systems are scarce and are either host specific or dedicated to specific pathogens.</p> <p>Results</p> <p>Here we describe "HPIDB” a host-pathogen PPI database, which will serve as a unified resource for host-pathogen interactions. Specifically, HPIDB integrates experimental PPIs from several public databases into a single, non-redundant web accessible resource. The database can be searched with a variety of options such as sequence identifiers, symbol, taxonomy, publication, author, or interaction type. The output is provided in a tab delimited text file format that is compatible with Cytoscape, an open source resource for PPI visualization. HPIDB allows the user to search protein sequences using BLASTP to retrieve homologous host/pathogen sequences. For high-throughput analysis, the user can search multiple protein sequences at a time using BLASTP and obtain results in tabular and sequence alignment formats. The taxonomic categorization of proteins (bacterial, viral, fungi, etc.) involved in PPI enables the user to perform category specific BLASTP searches. In addition, a new tool is introduced, which allows searching for homologous host-pathogen interactions in the HPIDB database. </p> <p>Conclusions</p> <p>HPIDB is a unified, comprehensive resource for host-pathogen PPIs. The user interface provides new features and tools helpful for studying host-pathogen interactions. HPIDB can be accessed at <url>http://agbase.msstate.edu/hpi/main.html</url>.</p

Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance

A glycosylphosphatidylinositol-anchored carbonic anhydrase-related protein of Toxoplasma gondii is important for rhoptry biogenesis and virulence

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries

Boosting in planta production of antigens derived from the porcine reproductive and respiratory syndrome virus (PRRSV) and subsequent evaluation of their immunogenicity

Porcine reproductive and respiratory syndrome (PRRS) is a disease of swine, caused by an arterivirus, the PRRS virus (PRRSV). This virus infects pigs worldwide and causes huge economic losses. Due to genetic drift, current vaccines are losing their power. Adaptable vaccines could provide a solution to this problem. This study aims at producing in planta a set of antigens derived from the PRRSV glycoproteins (GPs) to be included in a subunit vaccine. We selected the GP3, GP4 and GP5 and optimized these for production in an Arabidopsis seed platform by removing transmembrane domains (Tm) and/or adding stabilizing protein domains, such as the green fluorescent protein (GFP) and immunoglobulin (IgG) 'Fragment crystallizable' (Fc) chains. Accumulation of the GPs with and without Tm was low, reaching no more than 0.10% of total soluble protein (TSP) in homozygous seed. However, addition of stabilizing domains boosted accumulation up to a maximum of 2.74% of TSP when GFP was used, and albeit less effectively, also the Fc chains of the porcine IgG3 and murine IgG2a increased antigen accumulation, to 0.96% and 1.81% of TSP respectively, while the murine IgG3 Fc chain did not. Antigens with Tm were less susceptible to these manipulations to increase yield. All antigens were produced in the endoplasmic reticulum and accordingly, they carried high-mannose N-glycans. The immunogenicity of several of those antigens was assessed and we show that vaccination with purified antigens did elicit the production of antibodies with virus neutralizing activity in mice but not in pigs

ConsensusPathDB: toward a more complete picture of cell biology

ConsensusPathDB is a meta-database that integrates different types of functional interactions from heterogeneous interaction data resources. Physical protein interactions, metabolic and signaling reactions and gene regulatory interactions are integrated in a seamless functional association network that simultaneously describes multiple functional aspects of genes, proteins, complexes, metabolites, etc. With 155,432 human, 194,480 yeast and 13,648 mouse complex functional interactions (originating from 18 databases on human and eight databases on yeast and mouse interactions each), ConsensusPathDB currently constitutes the most comprehensive publicly available interaction repository for these species. The Web interface at http://cpdb.molgen.mpg.de offers different ways of utilizing these integrated interaction data, in particular with tools for visualization, analysis and interpretation of high-throughput expression data in the light of functional interactions and biological pathways

ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to the host-cell infection. We perform comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses to analyze in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors