bluuebunny/crossref_metadata_2025_split huggingface dataset:
Y2, the Smallest of the Sendai Virus C Proteins, Is Fully Capable of both Counteracting the Antiviral Action of Interferons and Inhibiting Viral RNA Synthesis
Authors: Kato Atsushi , Ohnishi Yukano , Kohase Masayoshi , Saito Sakura , Tashiro Masato , Nagai Yoshiyuki 
Published: July 2002

ABSTRACT

An open reading frame (ORF) overlapping the amino-terminal portion of the Sendai virus (SeV)
P
ORF in the +1 frame produces a nested set of carboxy-coterminal proteins, C′, C, Y1, and Y2, which are referred to collectively as the C proteins. The C proteins are extremely versatile triple-role players; they counteract the antiviral action of interferons (IFNs), inhibit viral RNA synthesis, and are involved in virus assembly. In this study, we established HeLa cell lines stably expressing the C, Y1, and Y2 proteins individually and examined the capacities of these cells to circumvent the antiviral action of alpha/beta IFN (IFN-α/β) and IFN-γ and to inhibit viral transcription. The assay protocols included monitoring of IFN-α/β-mediated signaling by interferon-stimulated response element-driven reporter gene expression and of the antiviral state induced by IFN-α/β and IFN-γ and measurement of reporter gene expression from an SeV minigenome, as well as quantification of SeV primary transcripts. When necessary, the activities measured were carefully normalized to the expression levels of the respective C proteins in cells. The data obtained clearly indicate that the smallest protein, Y2, was as active as the C and Y1 proteins in both counteracting the antiviral action of IFNs and inhibiting viral transcription. The data further show that intracellular transexpression of either C, Y1, or Y2 rendered HeLa cells moderately or only poorly permissive for not only wild-type SeV but also 4C(−) SeV, which expressed none of the four C proteins. On the basis of these findings, the roles of SeV C proteins in the natural life cycle are discussed.
Sites and Determinants of Early Cleavages in the Proteolytic Processing Pathway of Reovirus Surface Protein σ3
Authors: Jané-Valbuena Judit , Breun Laura A. , Schiff Leslie A. , Nibert Max L. 
Published: July 2002

ABSTRACT
Entry of mammalian reovirus virions into target cells requires proteolytic processing of surface protein σ3. In the virion, σ3 mostly covers the membrane-penetration protein μ1, appearing to keep it in an inactive form and to prevent it from interacting with the cellular membrane until the proper time in infection. The molecular mechanism by which σ3 maintains μ1 in this inactive state and the structural changes that accompany σ3 processing and μ1 activation, however, are not well understood. In this study we characterized the early steps in σ3 processing and determined their effects on μ1 function and particle infectivity. We identified two regions of high protease sensitivity, “hypersensitive” regions located at residues 208 to 214 and 238 to 244, within which all proteases tested selectively cleaved σ3 as an early step in processing. Further processing of σ3 was required for infection, consistent with the fact that the fragments resulting from these early cleavages remained bound to the particles. Reovirus type 1 Lang (T1L), type 3 Dearing (T3D), and T1L × T3D reassortant virions differed in the sites of early σ3 cleavage, with T1L σ3 being cleaved mainly at residues 238 to 244 and T3D σ3 being cleaved mainly at residues 208 to 214. These virions also differed in the rates at which the early cleavages occurred, with cleavage of T1L σ3 occurring faster than cleavage of T3D σ3. Analyses using chimeric and site-directed mutants of recombinant σ3 identified carboxy-proximal residues 344, 347, and 353 as the primary determinants of these strain differences. The spatial relationships between these more carboxy-proximal residues and the hypersensitive regions were discerned from the σ3 crystal structure. The results indicate that proteolytic processing of σ3 during reovirus disassembly is a multistep pathway with a number of molecular determinants.
Cation-Independent Mannose 6-Phosphate Receptor Blocks Apoptosis Induced by Herpes Simplex Virus 1 Mutants Lacking Glycoprotein D and Is Likely the Target of Antiapoptotic Activity of the Glycoprotein
Authors: Zhou Guoying , Roizman Bernard 
Published: July 2002

ABSTRACTHerpes simplex virus 1 mutants lacking the gene encoding glycoprotein D (gD) and the gD normally present in the envelope of the virus (gD−/−stocks) or mutants lacking the gD gene but containingtrans-induced gD in their envelopes (gD−/+) cause apoptosis in human SK-N-SH cells. The gD−/−virions are taken up by endocytosis and are degraded, whereas gD−/+viruses replicate but produce gD−/−virus. Apoptosis is blocked by delivery of the gD gene intrans. Studies designed to test several hypotheses concerning the role of gD in apoptosis revealed the following. (i) gD−/−and gD−/+stocks induce fragmentation of cellular DNA in SK-N-SH, HEp-2, HeLa, and Vero cell lines. (ii) Chloroquine blocks apoptosis induced by gD−/−stocks but not by gD−/+stocks. The drug also rescues gD−/−from degradation. (iii) Cells transduced with cation-independent mannose 6-phosphate receptor (CI-MPR) block apoptosis induced by either gD−/−or gD−/+virus. (iv) Expression of sequences antisense to the cloned CI-MPR gene induced apoptosis by themselves. Wild-type virus but not gD−/−or gD−/+stocks of mutant virus blocked apoptosis induced by the expression of CI-MPR antisense sequences. These results exclude the possibility that to block apoptosis, gD must interact with its HveA receptor, a member of the tumor necrosis factor alpha receptor family. Instead, the data suggest that gD blocks the influx of lysosomal enzymes into the endosomal compartment by binding to CI-MPR. This conclusion is consistent with published reports that phosphorylated gD interacts with CI-MPR.
The Genome of Swinepox Virus
Authors: Afonso C. L. , Tulman E. R. , Lu Z. , Zsak L. , Osorio F. A. , Balinsky C. , Kutish G. F. , Rock D. L. 
Published: July 2002

ABSTRACT

Swinepox virus
(SWPV), the sole member of the
Suipoxvirus
genus of the
Poxviridae
, is the etiologic agent of a worldwide disease specific for swine. Here we report the genomic sequence of SWPV. The 146-kbp SWPV genome consists of a central coding region bounded by identical 3.7-kbp inverted terminal repeats and contains 150 putative genes. Comparison of SWPV with chordopoxviruses reveals 146 conserved genes encoding proteins involved in basic replicative functions, viral virulence, host range, and immune evasion. Notably, these include genes with similarity to genes for gamma interferon (IFN-γ) receptor, IFN resistance protein, interleukin-18 binding protein, IFN-α/β binding protein, extracellular enveloped virus host range protein, dUTPase, hydroxysteroid dehydrogenase, superoxide dismutase, serpin, herpesvirus major histocompatibility complex inhibitor, ectromelia virus macrophage host range protein, myxoma virus M011L, variola virus B22R, four ankyrin repeat proteins, three kelch-like proteins, five vaccinia virus (VV) A52R-like family proteins, and two G protein-coupled receptors. The most conserved genomic region is centrally located and corresponds to the VV region located between genes F9L and A38L. Within the terminal 13 kbp, colinearity is disrupted and multiple poxvirus gene homologues are absent or share a lower percentage of amino acid identity. Most of these differences involve genes and gene families with likely functions involving viral virulence and host range. Three open reading frames (SPV018, SPV019. and SPV020) are unique for SWPV. Phylogenetic analysis, genome organization, and amino acid identity indicate that SWPV is most closely related to the capripoxvirus lumpy skin disease virus, followed by the yatapoxvirus yaba-like disease virus and the leporipoxviruses. The gene complement of SWPV better defines
Suipoxvirus
within the
Chordopoxvirinae
subfamily and provides a basis for future genetic comparisons.
Endoplasmic Reticulum-Golgi Intermediate Compartment Membranes and Vimentin Filaments Participate in Vaccinia Virus Assembly
Authors: Risco Cristina , Rodríguez Juan R. , López-Iglesias Carmen , Carrascosa José L. , Esteban Mariano , Rodríguez Dolores 
Published: July 2002

ABSTRACT
Vaccinia virus (VV) has a complex morphogenetic pathway whose first steps are poorly characterized. We have studied the early phase of VV assembly, when viral factories and spherical immature viruses (IVs) form in the cytoplasm of the infected cell. After freeze-substitution numerous cellular elements are detected around assembling viruses: membranes, ribosomes, microtubules, filaments, and unidentified structures. A double membrane is clearly resolved in the VV envelope for the first time, and freeze fracture reveals groups of tubules interacting laterally on the surface of the viroplasm foci. These data strongly support the hypothesis of a cellular tubulovesicular compartment, related to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), as the origin of the first VV envelope. Moreover, the cytoskeletal vimentin intermediate filaments are found around viral factories and inside the viroplasm foci, where vimentin and the VV core protein p39 colocalize in the areas where crescents protrude. Confocal microscopy showed that ERGIC elements and vimentin filaments concentrate in the viral factories. We propose that modified cellular ERGIC membranes and vimentin intermediate filaments act coordinately in the construction of viral factories and the first VV form through a unique mechanism of viral morphogenesis from cellular elements.
A Replication-Competent, Neutralization-Sensitive Variant of Simian Immunodeficiency Virus Lacking 100 Amino Acids of Envelope
Authors: Johnson Welkin E. , Morgan Jennifer , Reitter Julie , Puffer Bridget A. , Czajak Susan , Doms Robert W. , Desrosiers Ronald C. 
Published: July 2002

ABSTRACT

Coding sequences for the first two variable loops of the gp120 envelope glycoprotein were removed from simian immunodeficiency virus (SIV) strain 239 (SIVmac239). This deletion encompassed 100 amino acids. The resulting virus replicated poorly after transfection into immortalized T-cell lines, with peak replication occurring only after 25 to 30 days. Limited passaging of SIVmac239ΔV1V2 in cultures gave rise to a variant which had significantly improved replication kinetics but which retained the original 100-amino-acid deletion in gp120. Cloning and sequencing revealed 11 changes in the envelope, including amino acid substitutions in both gp120 (5 substitutions) and gp41(6 substitutions). Four of the five changes in gp120 are predicted to lie within and around the putative coreceptor binding domain, a region which is believed to be covered by the V1 and V2 loops in the native envelope complex. Analysis of recombinant clones surprisingly revealed that the changes in gp41 were sufficient to overcome the replication deficiency created by deletion of the V1 and V2 loops from gp120. The SIVmac239ΔV1V2 envelope displayed a significant reduction in its ability to mediate cell-cell fusion, and the infectious titer of SIVmac239ΔV1V2 was approximately four- to eightfold lower than that of parental SIVmac239. Although SIVmac239 is strongly dependent on both CD4 and a coreceptor for entry, envelope protein lacking the V1 and V2 loops was able to mediate fusion with CD4
−
CCR5
+
cells at 60% the level observed with CD4
+
CCR5
+
cells. Plasma from SIVmac239-infected monkeys was at least 100 to 1,000 times more effective at neutralizing SIVmac239ΔV1V2 than SIVmac239. These results demonstrate the dispensability of the V1-V2 sequences of SIVmac239 for viral replication, a role for V1 and V2 in shielding the coreceptor binding region of the envelope, and the extreme sensitivity of a SIV lacking these sequences to antibody-mediated neutralization.
Endocytosis of Adeno-Associated Virus Type 5 Leads to Accumulation of Virus Particles in the Golgi Compartment
Authors: Bantel-Schaal Ursula , Hub Birgit , Kartenbeck Juergen 
Published: July 2002

ABSTRACT
Among the adeno-associated virus (AAV) serotypes which are discussed as vectors for gene therapy AAV type 5 (AAV5) represents a candidate with unique advantages. To further our knowledge on AAV5-specific characteristics, we studied the entry pathway of wild-type virus in HeLa cells in the absence of helper virus by immunofluorescence and electron microscopy and by Western blot analysis. We found virus binding at the apical cell surface, especially at microvilli and, with increasing incubation time, virus accumulation at cell-cell boundaries. The different binding kinetics suggest different binding properties at apical versus lateral plasma membranes. Endocytosis of viruses was predominantly by clathrin-coated vesicles from both membrane domains; however, particles were also detected in noncoated pits. AAV5 particles were mainly routed to the Golgi area, where they could be detected within cisternae of the trans-Golgi network and within vesicles associated with cisternae and with the dictyosomal stacks of the Golgi apparatus. These data suggest that AAV5 makes use of endocytic routes that have hitherto not been described as pathways for virus entry.
Ebola Virus Glycoproteins Induce Global Surface Protein Down-Modulation and Loss of Cell Adherence
Authors: Simmons Graham , Wool-Lewis Rouven J. , Baribaud Frédéric , Netter Robert C. , Bates Paul 
Published: July 2002

ABSTRACT
The Ebola virus envelope glycoprotein (GP) derived from the pathogenic Zaire subtype mediates cell rounding and detachment from the extracellular matrix in 293T cells. In this study we provide evidence that GPs from the other pathogenic subtypes, Sudan and Côte d'Ivoire, as well as from Reston, a strain thought to be nonpathogenic in humans, also induced cell rounding, albeit at lower levels than Zaire GP. Sequential removal of regions of potential O-linked glycosylation at the C terminus of GP1 led to a step-wise reduction in cell detachment without obviously affecting GP function, suggesting that such modifications are involved in inducing the detachment phenotype. While causing cell rounding and detachment in 293T cells, Ebola virus GP did not cause an increase in cell death. Indeed, following transient expression of GP, cells were able to readhere and continue to divide. Also, the rounding effect was not limited to 293T cells. Replication-deficient adenovirus vectors expressing Ebola virus GP induced the loss of cell adhesion in a range of cell lines and primary cell types, including those with proposed relevance to Ebola virus infection in vivo, such as endothelial cells and macrophages. In both transfected 293T and adenovirus-infected Vero cells, a reduction in cell surface expression of adhesion molecules such as integrin β1 concurrent with the loss of cell adhesion was observed. A number of other cell surface molecules, however, including major histocompatibility complex class I and the epidermal growth factor receptor, were also down-modulated, suggesting a global mechanism for surface molecule down-regulation.
Capsid-Specific Cytotoxic T Lymphocytes Recognize Three Distinct H-2Db-Restricted Regions of the BeAn Strain of Theiler's Virus and Exhibit Different Cytokine Profiles
Authors: Lyman Michael A. , Lee Hee-Gu , Kang Bong Su , Kang Hee-Kap , Kim Byung S. 
Published: July 2002

ABSTRACTThe role of virus-specific cytotoxic T lymphocytes (CTL) in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a viral model for multiple sclerosis, is not yet clear. To investigate the specificity and function of CTL generated in response to TMEV infection, we generated a panel of overlapping 20-mer peptides encompassing the entire capsid and leader protein region of the BeAn strain of TMEV. Binding of these peptides to H-2Kband H-2Dbclass I molecules of resistant mice was assessed using RMA-S cells. Several peptides displayed significant binding to H-2Kb, H-2Db, or both. However, infiltrating cytotoxic T cells in the central nervous system of virus-infected mice preferentially lysed target cells pulsed with VP2111-130/121-140or VP2121-130, a previously defined CTL epitope shared by the DA strain of TMEV and other closely related cardioviruses. In addition, at a high effector-to-target cell ratio, two additional peptides (VP2161-180and VP3101-120) sensitized target cells for cytolysis by infiltrating T cells or splenic T cells from virus-infected mice. The minimal epitopes within these peptides were defined as VP2165-173and VP3110-120. Based on cytokine profiles, CTL specific for these subdominant epitopes are Tc2, in contrast to CTL for the immunodominant epitope, which are of the Tc1 type. Interestingly, CTL function towards both of these subdominant epitopes is restricted by the H-2D molecule, despite the fact that these epitopes bind both H-2K and H-2D molecules. This skewing toward an H-2Db-restricted response may confer resistance to TMEV-induced demyelinating disease, which is known to be associated with theH-2Dgenetic locus.
Exercise and outdoor ambient air pollution
Authors: Carlisle A J , Sharp N C C 
Published: July 2002

Objectives—To establish by literature survey: (a) levels at which air pollutants are considered damaging to human health and to exercisers in particular; (b) the current ambient levels experienced in the United Kingdom; (c) whether athletes are especially at risk.Methods—Six major urban air pollutants were examined: carbon monoxide (CO); nitrogen oxides (NOX); ozone (O3); particulate matter (PM10); sulphur dioxide (SO2); volatile organic compounds (VOCs).Results—CO is detrimental to athletic performance. NO2is of concern to human health, but outdoor levels are low. O3poses a potentially serious risk to exercising athletes. Decrements in lung function result from exposure, and there is evidence that athletic performance may be affected. Detrimental effects may occur at low ambient levels, but there is no scientific consensus on this matter. PM10is causing concern in the scientific community. Blood lead accumulation during exercise indicates that personal exposure to toxic compounds associated with PM10may be magnified. Generally, outdoor ambient levels of SO2are too low to cause a problem to the athlete, except the asthmatic athlete. The few studies on exposure of exercisers to VOCs are reviewed.Conclusions—Athletes and exercisers should avoid exercising by the road side even though levels of the more noxious air pollutants have been controlled in the United Kingdom. O3is particularly damaging to athletes; it reaches its highest concentrations on hot bright days in rural areas.
Dramatic diurnal variation in the concentration of the human trefoil peptide TFF2 in gastric juice
Authors: Semple J I , Newton J L , Westley B R , May F E B 
Published: July 2002

BACKGROUNDTFF2, a member of the trefoil factor family of proteins, is a glycosylated protein of 106 amino acids. It is secreted by gastric antral and pyloric glands and by Brunner's glands of the duodenum. TFF2 is found in high concentrations around sites of ulceration. It stimulates cell motility and is probably the principal cytoprotective trefoil peptide in the stomach.AIMSTo determine if production of TFF2 follows a circadian rhythm and to measure changes in secretion of TFF2 in response to food intake and during sleep.SUBJECTSYoung healthy adults were recruited. They were asymptomatic and were not receiving medication. The 24 hour regimen was designed to allow normal stimulation of gastric secretion in response to food intake and sleep. Gastric juice was collected two hourly via a nasogastric tube.METHODSGlycosylated and non-glycosylated TFF2 proteins were measured by quantitative western transfer analysis. The results were analysed statistically using SPSS software.RESULTSThere was a dramatic diurnal variation in the concentration of TFF2. The mean concentration was lowest in the early evening (0.29 μg/ml), increased gradually during the evening, and then sharply during the night to reach 7.9 μg/ml. The ratio of glycosylated to non-glycosylated TFF2 varied and was higher during the night than in the afternoon. pH, total protein, and pepsin concentrations in gastric juice did not vary significantly over 24 hours.CONCLUSIONThe data suggest that diurnal variations in TFF2 secretion occur independently of pepsin and gastric acid secretion. The concentration of glycosylated TFF2 in the gastric lumen falls in response to food intake. TFF2 secretion increases during inactivity and sleep. These results suggest that secretion of TFF2 in the stomach is highest during the night and that the cytoprotective effects of TFF2 on the gastric mucosa occur mainly during sleep.
Exposure of Paris taxi drivers to automobile air pollutants within their vehicles
Authors: Zagury Emmanuelle , Le Moullec Yvon , Momas Isabelle 
Published: July 2002

OBJECTIVESTo study the exposure of Parisian taxi drivers to automobile air pollutants during their professional activity.METHODSA cross sectional study was carried out from 27 January to 27 March 1997, with measurements performed in the vehicles of 29 randomly selected drivers. Carbon monoxide (CO) content was measured over an 8 hour period by a CO portable monitor. The fine suspended particles were measured according to the black smoke index (BS), with a flow controlled portable pump provided with a cellulose filter. The nitrogen oxides, NO and NO2were measured with a passive sampler.RESULTSThese drivers are exposed during their professional activity to relatively high concentrations of pollutants (mean, median (SD) 3.8, 2 (1.7) ppm for CO, 168, 164 (53) μg/m3for BS, 625, 598 (224) μg/m3for NO, and 139, 131 (43) μg/m3for NO2.) For CO the concentrations were clearly lower than the threshold values recommended by the World Health Organisation. The situation is less satisfactory for the other pollutants, especially for the BS index. All concentrations of pollutants recorded were noticeably higher than concentrations in air recorded by the ambient Parisian air monitoring network and were close to, or slightly exceeded, the concentrations measured at the fixed stations close to automobile traffic. Pollutant concentrations were also influenced greatly by weather conditions.CONCLUSIONThis first French study conducted in taxi drivers shows that they are highly exposed to automobile pollutants. The results would justify a medical follow up of this occupational group.
Carbohydrate-deficient glycoprotein syndromes
Authors: Gordon Neil 
Published: July 2002

SummaryFour types of carbohydrate-deficient glycoprotein syndrome have been described, and the cause of two of them has been found. The symptoms and signs of these syndromes are described, with variations that occur at different ages. The commonest is type Ia with an autosomal recessive form of inheritance, and the gene responsible has been mapped to 16p. The typical pathology is atrophy of the cerebellum and brainstem, sometimes also involving the cortex, although both the pathology and the biochemical deficiencies vary between different types of syndrome. The diagnosis depends firstly on recognising the clinical features, including the presence of complications such as thyroid disorders. Then biochemical tests can be carried out, especially chromatographic carbohydrate-deficient transferrin assay and isoelectric focusing of serum transferrin.The prognosis depends on the complications, renal, hepatic, and cardiac, but affected children will be severely handicapped. Therefore treatment consists mainly of coping with the complications, and supporting the child and the family. Oral infusion of mannose can be effective in type Ib disease.