A Host YB-1 Ribonucleoprotein Complex Is Hijacked by Hepatitis C Virus for the Control of NS3-Dependent Particle Production

Hepatitis C virus (HCV) orchestrates the different stages of its life cycle in time and space through the sequential participation of HCV proteins and cellular machineries; hence, these represent tractable molecular host targets for HCV elimination by combination therapies. We recently identified multifunctional Y-box-binding protein 1 (YB-1 or YBX1) as an interacting partner of NS3/4A protein and HCV genomic RNA that negatively regulates the equilibrium between viral translation/replication and particle production. To identify novel host factors that regulate the production of infectious particles, we elucidated the YB-1 interactome in human hepatoma cells by a quantitative mass spectrometry approach. We identified 71 YB-1-associated proteins that included previously reported HCV regulators DDX3, heterogeneous nuclear RNP A1, and ILF2. Of the potential YB-1 interactors, 26 proteins significantly modulated HCV replication in a gene-silencing screening. Following extensive interaction and functional validation, we identified three YB-1 partners, C1QBP, LARP-1, and IGF2BP2, that redistribute to the surface of core-containing lipid droplets in HCV JFH-1-expressing cells, similarly to YB-1 and DDX6. Importantly, knockdown of these proteins stimulated the release and/or egress of HCV particles without affecting virus assembly, suggesting a functional YB-1 protein complex that negatively regulates virus production. Furthermore, a JFH-1 strain with the NS3 Q221L mutation, which promotes virus production, was less sensitive to this negative regulation, suggesting that this HCV-specific YB-1 protein complex modulates an NS3-dependent step in virus production. Overall, our data support a model in which HCV hijacks host cell machinery containing numerous RNA-binding proteins to control the equilibrium between viral RNA replication and NS3-dependent late steps in particle production.     

The ultrastructural characteristics of the motor neuron synaptic organization in the spinal cord of the frog Rana ridibunda

Electron microscopic studies on the spinal motor nuclei in amphibians indicate significant diversity in chemical synapses formed on motoneurones by axonal endings of supra- and intraspinal systems. High ultrastructural specialization was observed among axosomatic, axodendritic and axoaxonal synapses. Several types of axo-spine synapses and axodentritic synaptic complexes of the "glomerular" type were revealed. New data on ultrastructural peculiarities of chemical synapses presented in this paper, together with earlier detailed data on morphologically mixed and electrotonic synapses, increase our knowledge of evolutionary trends in synaptic organization of motoneurones in the spinal cord and suggest the existence of a complex mechanism of integration of synaptic influences in the spinal cord of lower vertebrates.     

Influence of Iron Oxide-Based Nanoparticles with Various Shell Modifications on the Generation of Reactive Oxygen Species in Stimulated Human Blood Cells in vitro

Journal of Evolutionary Biochemistry and Physiology - Among the available nanoparticles, those based on iron oxide are of particular interest due to their biological safety, magnetic properties,...     

Distribution of reticulospinal fibers and theri endings in the lumbar segments of the rat spinal cord]

After stereotaxis lexions in the nucleus reticularis gigantocellularis of the modulla oblongata and nucleus reticularis pontis caudalis, the distribution of degenerating nerve fibers in the lumbar segments of the spinal cord has been studied by silver impregnation methods of Nauta and Fink-Heimer. Degenerating reticulo-spinal fibers and fragments of axonal terminations were found in the area of n. motorius ventro-medialis and n. motorius ventro-lateralis, as well as partly in n. motorius dorso-lateralis close to motoneurons and their dendrites. Mainly they pass into layers VII and VIII. This fact indicates the existence of direct-reticulo-motoneuronal synaptic connections in rats, which coincides with electrophysiological data.     

Investigation of synaptic connections between primary afferents and motoneurons in the frog spinal cord by intracellular injection of horseradish peroxidase

Parallel recordings of potentials from primary afferent fibers and motoneurons connected monosynaptically with them were obtained in experiments on the isolated, perfused frog spinal cord and this was followed by intra-axonal and intracellular injection of horseradish peroxidase. Terminals of the primary afferent fibers were shown to reach the motor nuclei of the ventral horn, and one fiber could form contacts with several motoneurons. Synapses formed by afferent terminals were found not only on distal, but also on proximal segments of dendrites and also on motoneuron bodies. Synapses were most numerous on the proximal segments of the dendrites and branches of the second-third orders. Recurrent axon collaterals of motoneurons forming synapses with dendrites were found.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 14, No. 1, pp. 60–68, January–February, 1982.     

Electrotonic synapses in the mammalian spinal cord

By means of light and electron microscopy methods structural peculiarities of motor nuclei have been studied in the rat spinal cord (17 animals) on the 1st-3d and on the 10th-18th days of postnatal ontogenesis. Synaptic junctions of the gap type are revealed; they are considered as electrotonic synapses. Dendro-somatic and dendrodendritic synaptic junctions of the gap type are found. Together with the electrotonic synapses, morphologically mixed synapses of axo-somatic and axo-axonal types are disclosed; they contain, besides organells, specific for chemical synapses, close opposition areas of pre- and postsynaptic membranes of the gap junction type. Morphologically mixed synapses occur in neuropil of the motor nuclei of the spinal cord in young rats of all age groups studied. Homologous synapses are detected in the motor nuclei of the white mouse spinal cord. Synaptic junctions of the gap type in the mammalian spinal cord could be a substrate of electrical interaction between its motor neurons.     

Peculiarities of the staining of neural tissue with procion yellow]

The application of protion yellow allowed to reveal nerve cells of different size, and their dendrites and axons, bundles of nerve fibres for a considerable length. Staining with protional yellow resembles to impregnation of the nervous tissue with silver salts. Combination of protion yellow with dyes of other groups and silver nitrate impregnation improves the stability of staining.     

Distribution of alpha-amylase isozymes among the varieties of winter wheat in Russia and Ukraine

A catalog of winter wheat varieties bred in Russia and Ukraine for alpha-amylase isozymes is presented. Among them, 11 phenotypic classes were found. It was established that the observed differences in the frequency of specific phenotypes for alpha-amylase in the culture of winter wheat depended on the geographical origin. The percentage of the most widespread cultural phenotype, designated as AbCde, decreased from the south (45°–46° N) to the north (49°–50° N) by 31.0%. At the same time, the frequency of the abCde variant increased by 25.0%. The distribution of the Abcde phenotype changed significantly from 20.7% in the west (30o36′ E) to 0% in the east (40o18′ E). The observed territorial dynamics for alpha-amylase isoenzymes may indicate the adaptive value of the identified phenotypes of common winter wheat for the weather and climatic conditions of the region of their origin.