PLoS Pathog

Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV). To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes

Hepatitis C virus infection protein network

A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein–protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFβ pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins

ViralORFeome: an integrated database to generate a versatile collection of viral ORFs

Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such ‘ORFeome’ resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway® system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins

METHODS FOR SCREENING SUBSTANCES CAPABLE OF MODULATING THE REPLICATION OF AN INFLUENZA VIRUS

The present invention relates to methods for screening substances capable of modulating the replication of an influenza virus. More particularly, the present invention relates to methods for screening a plurality of substances capable of modulating the replication of an influenza virus in a host cell comprising the step consisting of identifying a substance that modulates the specific interaction of a host cell protein with a viral protein required for viral replication as depicted in table 1 or identifying a substance that modulates the specific interaction of a first host cell protein as depicted in table 1 with a second host cell protein present in cellular network of the first host cell protein or identifying a substance that modulates the expression of a host cell protein as depicted in table 1, or identifying a substance that modulates the activity of a host cell protein as depicted in table 1info:eu-repo/semantics/publishe

Fatigue crack nuclei in austempered ductile cast iron

Short fatigue crack nuclei in austempered ductile cast iron have been studied using optical microscopy, scanning electron microscopy, atomic force microscopy and X-ray microtomography and by electron backscatter diffraction analysis. Fatigue cracks nucleate at graphite nodules and shrinkage microporosity. The crack nuclei are arrested and retarded by barriers in the microstructure, by either blocking of slip at boundaries or owing to the requirement for tilt and twist of the stage I crystallographic crack at grain boundaries. These observations indicate that both the size of the defects, such as graphite nodules and microporosity, and the size of the prior austenite grains control the largest crack nucleus that can develop, and hence determine the component fatigue limit