Hepatitis C virus E1 recruits high-density lipoprotein to support infectivity and evade antibody recognition.

Hepatitis C virus (HCV) is a member of the family; however, unlike other family members, the HCV virion has an unusually high lipid content. HCV has two envelope glycoproteins, E1 and E2. E2 contributes to receptor binding, cell membrane attachment, and immune evasion.

SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition.

Severe COVID-associated lung injury is a major confounding factor of hospitalizations and death with no effective treatments. Here, we describe a non-classical fibrin clotting mechanism mediated by SARS-CoV-2 infected primary lung but not other susceptible epithelial cells. This infection-induced fibrin formation is observed in all variants of SARS-CoV-2 infections, and requires thrombin but is independent of tissue factor and other classical plasma coagulation factors.

Functional human IgA targets a conserved site on malaria sporozoites.

Immunoglobulin (Ig)A antibodies play a critical role in protection against mucosal pathogens. However, the role of serum IgA in immunity to nonmucosal pathogens, such as , is poorly characterized, despite being the second most abundant isotype in blood after IgG. Here, we investigated the circulating IgA response in humans to sporozoites that are injected into the skin by mosquitoes and migrate to the liver via the bloodstream to initiate malaria infection.

Vaccinia Virus Ankyrin-Repeat/F-Box Protein Targets Interferon-Induced IFITs for Proteasomal Degradation.

IFITs are interferon-induced proteins that can bind 5'-triphosphate or ribose-unmethylated capped ends of mRNA to inhibit translation. Although some viruses avoid IFITs by synthesizing RNAs with eukaryotic-like caps, no viral proteins were known to antagonize IFITs. We show that the N- and C-terminal portions of C9, a protein required for vaccinia virus to resist the human type I interferon-induced state, bind IFITs and ubiquitin regulatory complexes, respectively.

Dynamic secondary electron emission in rough composite materials.

The interaction of ionizing radiation with matter is of critical importance in numerous areas of science and technology like space and vacuum technology and even medicine and biotechnology. Secondary electron emission is a consequence of electron irradiation on materials. We achieve extremely low secondary electron emission yield values smaller than 0.

Magnesium transporter 1 (MAGT1) deficiency causes selective defects in linked glycosylation and expression of immune-response genes.

Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches. In humans, loss-of-function mutations in the gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences. We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg transport.

Host cell protein quantification of an optimized purification method by mass spectrometry.

Recombinant ExoProtein A (EPA), a detoxified form of Pseudomonas aeruginosa Exotoxin A, is used as a protein carrier in the vaccine field. A scaled manufacturing process, in which EPA was expressed in Escherichia coli, yielded a product that approached or exceeded our upper limit of E. coli host cell protein (HCP) content per human dose.

Assessment of the impact of manufacturing changes on the physicochemical properties of the recombinant vaccine carrier ExoProtein A.

Efforts to develop a vaccine for the elimination of malaria include the use of carrier proteins to assemble monomeric antigens into nanoparticles to maximize immunogenicity. Recombinant ExoProtein A (EPA) is a detoxified form of Pseudomonas aeruginosa Exotoxin A which has been used as a carrier in the conjugate vaccine field. A pilot-scale process developed for purification of EPA yielded product that consistently approached a preset upper limit for host cell protein (HCP) content per human dose.

Identification of Vaccinia Virus Replisome and Transcriptome Proteins by Isolation of Proteins on Nascent DNA Coupled with Mass Spectrometry.

Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA synthesis. To investigate poxvirus replication and transcription from a new perspective, we incorporated 5-ethynyl-2'-deoxyuridine (EdU) into nascent DNA in cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to fluor- or biotin-azide and visualized by confocal, superresolution, and transmission electron microscopy.

CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells.

Cellular lysates from PPD donors have been reported to transfer tuberculin reactivity to naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms "transfer factor" and "DLE" were used to characterize the reactivity-transferring properties of lysates. Intrigued by these reported phenomena, we found that the cellular extract derived from antigen-specific memory CD8 T cells induces IL-6 from antigen-matched APCs.

Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis.

The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies.

Identification of Outer Membrane and Exoproteins of Carbapenem-Resistant Multilocus Sequence Type 258 Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae strains have emerged as a cause of life-threatening infections in susceptible individuals (e.g., transplant recipients and critically ill patients).

Interactions of the vaccinia virus A19 protein.

The A19 protein of vaccinia virus (VACV) is conserved among chordopoxviruses, expressed late in infection, packaged in the virus core, and required for a late step in morphogenesis. Multiple-sequence alignments of A19 homologs indicated conservation of a series of lysines and arginines, which could represent a nuclear localization or nucleic acid binding motif, and a pair of CXXC motifs that suggested a zinc finger or redox active sites. The importance of the CXXC motif was confirmed by cysteine-to-serine substitutions, which rendered the altered protein unable to trans-complement infectivity of a null mutant.

Proteomic analysis of nuclei dissected from fixed rat brain tissue using expression microdissection.

Expression microdissection (xMD) is a high-throughput, operator-independent technology that enables the procurement of specific cell populations from tissue specimens. In this method, histological sections are first stained for cellular markers via either chemical or immuno-guided methods, placed in close contact with an ethylene vinyl acetate (EVA) film, and exposed to a light source. The focal, transient heating of the stained cells or subcellular structures melts the EVA film selectively to the targets for procurement.

Fluctuating charge normal modes: An algorithm for implementing molecular dynamics simulations with polarizable potentials.

A new method for performing molecular dynamics simulations with fluctuating charge polarizable potentials is introduced. In fluctuating charge models, polarizability is treated by allowing the partial charges to be variables, with values that are coupled to charges on the same molecule as well as those on other molecules. The charges can be efficiently propagated in a molecular dynamics simulation using extended Lagrangian dynamics.

Hydration free energies and entropies for water in protein interiors.

Free energy calculations for the transfer of a water molecule from the pure liquid to an interior cavity site in a protein are presented. Two different protein cavities, in bovine pancreatic trypsin inhibitor (BPTI) and in the I76A mutant of barnase, represent very different environments for the water molecule: one which is polar, forming four water-protein hydrogen bonds, and one which is more hydrophobic, forming only one water-protein hydrogen bond. The calculations give very different free energies for the different cavities, with only the polar BPTI cavity predicted to be hydrated.