Surfynol 465 solutions with both types of solvents and obtained the values of R in D20 and H20 at 2.4 and 2.5 nm, respectively,26 which shows no significant difference as described above. To elucidate further the variation of R, which seems to depend on the kind of measurement, we are now preparing the NMR relaxation and thermodynamic measurements of Surfynol 465 and
Hepatitis C virus (HCV) utilizes cellular factors for efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of deubiquitinating enzymes (DUBs) or overexpression of nonspecific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up RNA interference (RNAi) screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR-122 cells) but not in a nonhepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responses in vitro and in vivo. We also found that USP15-deficient Huh7 cells showed reductions in the amounts of lipid droplets (LDs), and the addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and the formation of LDs. IMPORTANCE Although ubiquitination has been shown to play important roles in the HCV life cycle, the roles of deubiquitinating enzymes (DUBs), which cleave ubiquitin chains from their substrates, in HCV propagation have not been investigated. Here, we identified USP15 as a DUB regulating HCV propagation. USP15 showed no interaction with viral proteins and no participation in innate immune responses. Deficiency of USP15 in Huh7 cells resulted in suppression of the translation of HCV RNA and reduction in the amounts of lipid droplets, and the addition of fatty acids partially restored the production of infectious HCV particles. These data suggest that USP15 participates in HCV propagation in hepatic cells through the regulation of viral RNA translation and lipid metabolism.
Nano-materials, such as zeolites with nano-sized pores, are attractive new materials in industry, and are expected to offer a promising future efficient way to settle problems in environmental ecology as well. 1 It is important when developing such new materials for different purposes to evaluate physicochemical properties, such as the surface area, cage/pore structure, adsorption coefficient and surface distribution of metal ions. Surface area, for example, has usually been determined by a classical volumetric or gravimetric method, such as B.E.T. adsorption analysis using nitrogen as an adsorbent gas, and advanced techniques, such as an electronic microscope, SEM or TEM also, solid state NMR have recently been used to analyze the physicochemical properties of a surface in detail.129 Xe NMR has long been applied to analyze a porous structure in zeolites, 2 and quite recently the most interesting topic, hyperpolarized 129 Xe NMR, have emerged, in which the sensitivity can be enhanced by several orders by utilizing the optical pumping technique.3 It is highly expected that such a sensitivity enhanced 129 Xe NMR will be widely used to characterize nano-materials that have been newly synthesized, or of wide applicability in industry and medicine. In these 129 Xe NMR studies, basic parameters, such as the surface area and the adsorption energy are also hoped to be determined by using Xe as an adsorbent. 129 Xe NMR can be used for this purpose without any facilities of the traditional methodology, since it can provide a measure of the amount of adsorbed Xe through the intensity of the 129 Xe adsorbed signal. Therefore, in order to examine the applicability of 129 Xe NMR in obtaining basic adsorption parameters of the surface area and the adsorption energy for nano-materials, the temperature and pressure dependences are investigated for the chemical shift as well as the signal intensity, i.e., peak area, in the 129 Xe NMR of the present study. Experimental Reagents and chemicalsThe sample used was ZSM-5 (JRC-Z5-70Na from Mobil Catalysts Corp., Japan, Si/Al ratio = 92.5), supplied as a standard sample from Japan Catalysis Association. ZSM-5 is one of the micro-porous zeolites with an MFI structure, which is expected to contribute to improving the environment as an exchange agent for the separation of alcohol, NO removal etc. There is no super cage existing in ZSM-5, although X-or Ytype zeolite has them as the FAU structure. The pore size is 0.56 × 0.53 nm in linear structure and 0.55 × 0.51 nm in zigzag pore structure. Two structures are crossed with each other and form a 3D structure. Standard Xe gas that contains a natural abundance of 26.24%129 Xe was purchased from Japan Air Gases Ltd., and used after drying by passing over K-Na alloy, or passing through Minifine Purer supplied from Liquid Gas Co. Apparatus and procedureThe zeolite sample and Xe gas were treated in a fully shielded system made by glass-blowing. The sample was weighed into a Temperature and pressure dependences of the 129 Xe NMR chemical shift ...
Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8+ T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses.
033ChemInform Abstract Compared to those of TiO2 powder particles, showing the quantum size effect, TiO2 microcrystallites incorporated in the interlayer of montmorillonite having ca. 15-å pillar height show a ca. 0.58-eV blue shift in its absorption and fluorescence spectra. The difference in the excited energy levels between the two kinds of photocatalysts amounts to 0.36 eV, the TiO2/clay being higher than the TiO2 powder. The photocatalytic activities for decomposition of 2-propanol to give acetone and H2 and of m-carboxylic acids with up to 8 carbons to give the corresponding alkanes and CO2 are greater in the case of the pillared TiO2. However, the pillared TiO2 exhibits lower activities for decomposition of capric acid.
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