Project description:As a canonical lymphocyte antigen-6/urokinase-type plasminogen activator receptor Ly6/uPAR family protein, lymphocyte antigen 6 complex, locus E (LY6E), plays important roles in immunological regulation, T cell physiology, and oncogenesis. Emerging evidence indicates that LY6E is also involved in the modulation of viral infection. Consequently, viral infection and associated pathogenesis have been associated with altered LY6E gene expression. The interaction between viruses and the host immune system has offered insights into the biology of LY6E. In this review, we summarize the current knowledge of LY6E in the context of viral infection, particularly viral entry.
Project description:The innate antiviral response is integral in protecting the host against virus infection. Many proteins regulate these signaling pathways including ubiquitin enzymes. The ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes work together to link ubiquitin, a small protein, onto other ubiquitin molecules or target proteins to mediate various effector functions. The tripartite motif (TRIM) protein family is a group of E3 ligases implicated in the regulation of a variety of cellular functions including cell cycle progression, autophagy, and innate immunity. Many antiviral signaling pathways, including type-I interferon and NF-?B, are TRIM-regulated, thus influencing the course of infection. Additionally, several TRIMs directly restrict viral replication either through proteasome-mediated degradation of viral proteins or by interfering with different steps of the viral replication cycle. In addition, new studies suggest that TRIMs can exert their effector functions via the synthesis of unconventional polyubiquitin chains, including unanchored (non-covalently attached) polyubiquitin chains. TRIM-conferred viral inhibition has selected for viruses that encode direct and indirect TRIM antagonists. Furthermore, new evidence suggests that the same antagonists encoded by viruses may hijack TRIM proteins to directly promote virus replication. Here, we describe numerous virus-TRIM interactions and novel roles of TRIMs during virus infections.
Project description:Matrix metaloproteinase-2 (MMP-2) is an extracellular Zn2+ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed ten families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamic cross-correlation analysis indicated domain movements corresponding to the opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the molecular mechanics Poisson Boltzman surface area-interaction entropy (MMPBSA-IE) analysis method and revealed strong binding energies for the catalytic Zn2+ ion 1, Ca2+ ion 1, and Ca2+ ion 3 with significant conformational stability at the binding sites of Zn2+ ion 1 and Ca2+ ion 1. Ca2+ ion 2 diffuses freely away from its crystallographically defined binding site. Zn2+ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca2+ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain; however, the interacting residue sidechain carboxyl groups are outside of Ca2+ ion 3's coordination sphere.
Project description:This SuperSeries is composed of the following subset Series: GSE36461: MiRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) GSE36462: MiRNA profiling during infection with H7N7 influenza A virus (A/Ck/Germany/R28/H7N7/2003) GSE36553: mRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) Refer to individual Series
Project description:Constitution of a biobank of tissues, whole blood and plasma samples and stools to identify markers associated with treatment response, postoperative morbidity including neuro-cognitive and mood complications and prognosis of Inflammatory Bowel disease or colorectal cancer.
Project description:Herein, we have reported a novel quinazolin-based Schiff base chemosensor (E)-2-benzamido-N'-(1-(pyridin-2-yl)ethylidene)benzohydrazide (L). L has been designed, synthesised and characterised by 1H-NMR, IR spectroscopy, ESI-MS spectrometry and theoretical studies. The receptor showed appreciable colorimetric λmax shift for both Ni2+ and Zn2+ ions and fluorometric "turn on" response in presence of only Zn2+ ion. The Jobs plot analysis revealed that receptor forms 2 : 1 complex with both the ions Ni2+ and Zn2+, further confirmed by ESI-MS analysis. The single crystal structure of L-Ni2+ complex (1) has also been determined. The colorimetric detection limits were calculated to 7.9 nM and 7.5 nM respectively for Ni2+ and Zn2+ in methanol-Tris-HCl buffer medium (10 mM, pH 7.2, 1 : 1 v/v). The chemosensor L can be applied for the recovery of contaminated water samples.
Project description:Studies of the functional proteins encoded by the poxvirus genome provide information about the composition of the virus as well as individual virus-virus protein and virus-host protein interactions, which provides insight into viral pathogenesis and drug discovery. Widely used proteomic techniques to identify and characterize specific protein-protein interactions include yeast two-hybrid studies and coimmunoprecipitations. Recently, various mass spectrometry techniques have been employed to identify viral protein components of larger complexes. These methods, combined with structural studies, can provide new information about the putative functions of viral proteins as well as insights into virus-host interaction dynamics. For viral proteins of unknown function, identification of either viral or host binding partners provides clues about their putative function. In this review, we discuss poxvirus proteomics, including the use of proteomic methodologies to identify viral components and virus-host protein interactions. High-throughput global protein expression studies using protein chip technology as well as new methods for validating putative protein-protein interactions are also discussed.
Project description:To study virus-host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions-viral-viral or host-host interactions-are constantly targeted and inhibited by exogenous interfaces mediating viral-host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these "hub proteins" evolve. "Party hubs" have multiple interfaces; they establish simultaneous/stable (domain-domain) interactions, and tend to evolve slowly. On the other hand, "date hubs" have few interfaces; they establish transient/weak (domain-motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein-protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly changing their interface residues, either to evade or to optimize their binding capabilities. Apart from gaining and losing interactions via rewiring mechanisms, virus-host PINs also evolve via gene duplication (paralogy); conservation (orthology); horizontal gene transfer (HGT) (xenology); and molecular mimicry (convergence). The last sections of this review focus on PPI experimental approaches and their limitations, and provide an overview of sources of biomolecular data for studying virus-host protein interactions.
Project description:Viral studies have historically approached their phylogenetic analysis without consideration of the impact of the role the host plays in evolution. Our study examines host/viral interactions through analysis of the phylogenetic relationship between hantavirus genetic sequences and host cytochrome B sequences. Phylogenetic analysis of known Hantavirus genetic sequences were performed using PAUP 3.1.1 (vers. 4.0.0d64). Only sequences available through GENBANK were analyzed. Phylogenetic analysis of hantavirus sequences revealed distinct patterns based upon geographic area. These patterns coincided with the known ranges of reservoir hosts. Multiple hosts for individual viruses and multiple viruses in a single host species for hantaviruses have been described. This may be due to accidental exposure, host-switching, co-speciation, or broad co-accommodation. Since the host is the actual environment that the virus survives in, changes in the host over time could potentially directly influence changes in the virus. Multiple viruses and hosts collide in Southeastern Europe increasing the prospect of finding distinct viral/host relationships. Rodent Cytochrome B is very well conserved and can be used to tract host lineage. By tracking the relationship of infected hosts, we theorize that patterns in host DNA will emerge that will mirror patterns in viral sequences. This analysis of the host DNA could provide an understanding into the causes of variation in hantaviral sequences, pathogenicity, transmissibility, infectivity, viral range and expand our knowledge of viral/host interactions. Surveillance for viruses in the field should include analysis of the host DNA in combination with the viral analysis.