bluuebunny/crossref_metadata_2025_split huggingface dataset:
N
-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40
Authors: Campanero-Rhodes Maria A. , Smith Alicia , Chai Wengang , Sonnino Sandro , Mauri Laura , Childs Robert A. , Zhang Yibing , Ewers Helge , Helenius Ari , Imberty Anne , Feizi Ten 
Published: September 2007

ABSTRACT

Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that
N
-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the
N
-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.
Analysis of the Role of Autophagy in Replication of Herpes Simplex Virus in Cell Culture
Authors: Alexander Diane E. , Ward Stephen L. , Mizushima Noboru , Levine Beth , Leib David A. 
Published: September 2007

ABSTRACT
The herpes simplex virus type 1 (HSV-1) neurovirulence gene encoding ICP34.5 controls the autophagy pathway. HSV-1 strains lacking ICP34.5 are attenuated in growth and pathogenesis in animal models and in primary cultured cells. While this growth defect has been attributed to the inability of an ICP34.5-null virus to counteract the induction of translational arrest through the PKR antiviral pathway, the role of autophagy in the regulation of HSV-1 replication is unknown. Here we show that HSV-1 infection induces autophagy in primary murine embryonic fibroblasts and that autophagosome formation is increased to a greater extent following infection with an ICP34.5-deficient virus. Elimination of the autophagic pathway did not significantly alter the replication of wild-type HSV-1 or ICP34.5 mutants. The phosphorylation state of eIF2α and viral protein accumulation were unchanged in HSV-1-infected cells unable to undergo autophagy. These data show that while ICP34.5 regulates autophagy, it is the prevention of translational arrest by ICP34.5 rather than its control of autophagy that is the pivotal determinant of efficient HSV-1 replication in primary cell culture.
Varicella-Zoster Virus Modulates NF-κB Recruitment on Selected Cellular Promoters
Authors: El Mjiyad Nadia , Bontems Sébastien , Gloire Geoffrey , Horion Julie , Vandevenne Patricia , Dejardin Emmanuel , Piette Jacques , Sadzot-Delvaux Catherine 
Published: September 2007

ABSTRACTIntercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-α). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF-α was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (MeWo), leading to the following observations: (i) VZV inhibits the stimulation oficam-1mRNA synthesis; (ii) despite VZV-induced nuclear translocation of p65, p52, and c-Rel, p50 does not translocate in response to TNF-α; (iii) the nuclear p65 present in VZV-infected cells is no longer associated with p50 and is unable to bind the proximal NF-κB site of theicam-1promoter, despite an increased acetylation and accessibility of the promoter in response to TNF-α; and (iv) VZV induces the nuclear accumulation of the NF-κB inhibitor p100. VZV also inhibitsicam-1stimulation of TNF-α by strongly reducing NF-κB nuclear translocation in MRC5 fibroblasts. Taken together, these data show that VZV interferes with several aspects of the immune response by inhibiting NF-κB binding and the expression of target genes. Targeting NF-κB activation, which plays a central role in innate and adaptive immune responses, leads to obvious advantages for the virus, particularly in melanocytes, which are a site of viral replication in the skin.
Analysis of the Interaction of Primate Retroviruses with the Human RNA Interference Machinery
Authors: Lin Jennifer , Cullen Bryan R. 
Published: September 2007

ABSTRACTThe question of whether retroviruses, including human immunodeficiency virus type 1 (HIV-1), interact with the cellular RNA interference machinery has been controversial. Here, we present data showing that neither HIV-1 nor human T-cell leukemia virus type 1 (HTLV-1) expresses significant levels of either small interfering RNAs or microRNAs in persistently infected T cells. We also demonstrate that the retroviral nuclear transcription factors HIV-1 Tat and HTLV-1 Tax, as well as the Tas transactivator encoded by primate foamy virus, fail to inhibit RNA interference in human cells. Moreover, the stable expression of physiological levels of HIV-1 Tat did not globally inhibit microRNA production or expression in infected human cells. Together, these data argue that HIV-1 and HTLV-1 neither induce the production of viral small interfering RNAs or microRNAs nor repress the cellular RNA interference machinery in infected cells.
p53 and hTERT Determine Sensitivity to Viral Apoptosis
Authors: Nguyen Marie L. , Kraft Rachel M. , Aubert Martine , Goodwin Edward , DiMaio Daniel , Blaho John A. 
Published: September 2007

ABSTRACTApoptosis is a potent host defense against microbes. Most viruses have adapted strategies to counteract this response. Herpes simplex virus (HSV) produces a balance between pro- and antiapoptotic processes during infection. When antiapoptotic signals become limiting, infected cells die through HSV-dependent apoptosis (HDAP). Oncogenic pathways were previously implicated in HDAP susceptibility. Here, we exploited our ability to selectively express all, one, or no oncogenes in the well-defined HeLa cell system to dissect the requirements for HDAP. Human papillomavirus E6 and E7 oncogene expression was inhibited by the E2 viral repressor. Sole expression of E6 mediated HDAP sensitization. Next, two known cellular targets of E6 were independently modulated. This demonstrated that E6 sensitizes HeLa cells to HDAP through hTERT and p53. Given the universality of the apoptotic antiviral response, p53 and telomerase regulation will likely be important for counteracting host defenses in many other viral infections.
Norwalk Virus RNA Is Infectious in Mammalian Cells
Authors: Guix Susana , Asanaka Miyuki , Katayama Kazuhiko , Crawford Sue E. , Neill Frederick H. , Atmar Robert L. , Estes Mary K. 
Published: September 2007

ABSTRACT

Human noroviruses are positive-sense RNA viruses and are the leading cause of epidemic acute viral gastroenteritis in developed countries. The absence of an in vitro cell culture model for human norovirus infection has limited the development of effective antivirals and vaccines. Human histo-blood group antigens have been regarded as receptors for norovirus infection, and expression of the α(1,2) fucosyltransferase gene (
FUT2
) responsible for the secretor phenotype is required for susceptibility to Norwalk virus (NV) infection. We report for the first time that transfection of NV RNA, isolated from stool samples from human volunteers, into human hepatoma Huh-7 cells leads to viral replication, with expression of viral antigens, RNA replication, and release of viral particles into the medium. Prior treatment of the RNA with proteinase K completely abolishes RNA infectivity, suggesting a key role of an RNA-protein complex. Although overexpression of the human
FUT2
gene enhances virus binding to cells, it is not sufficient to allow a complete viral infection, and viral spread from NV-transfected cells to naïve cells does not occur. Finally, no differences in NV RNA replication are observed between Huh-7 and Huh-7.5.1 cells, which contain an inactivating mutation in retinoic acid-inducible gene I (RIG-I), suggesting that the RIG-I pathway does not play a role in limiting NV replication. Our results strongly suggest that the block(s) to NV replication in vitro is at the stage of receptor and/or coreceptor binding and/or uncoating, either because cells lack some specific factor or activation of cellular antiviral responses independent of RIG-I inhibits virus replication.
Localization and Membrane Topology of Coronavirus Nonstructural Protein 4: Involvement of the Early Secretory Pathway in Replication
Authors: Oostra M. , te Lintelo E. G. , Deijs M. , Verheije M. H. , Rottier P. J. M. , de Haan C. A. M. 
Published: September 2007

ABSTRACT
The coronavirus nonstructural proteins (nsp's) derived from the replicase polyproteins collectively constitute the viral replication complexes, which are anchored to double-membrane vesicles. Little is known about the biogenesis of these complexes, the membrane anchoring of which is probably mediated by nsp3, nsp4, and nsp6, as they contain several putative transmembrane domains. As a first step to getting more insight into the formation of the coronavirus replication complex, the membrane topology, processing, and subcellular localization of nsp4 of the mouse hepatitis virus (MHV) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were elucidated in this study. Both nsp4 proteins became N glycosylated, while their amino and carboxy termini were localized to the cytoplasm. These observations imply nsp4 to assemble in the membrane as a tetraspanning transmembrane protein with a Nendo/Cendo topology. The amino terminus of SARS-CoV nsp4, but not that of MHV nsp4, was shown to be (partially) processed by signal peptidase. nsp4 localized to the endoplasmic reticulum (ER) when expressed alone but was recruited to the replication complexes in infected cells. nsp4 present in these complexes did not colocalize with markers of the ER or Golgi apparatus, while the susceptibility of its sugars to endoglycosidase H indicated that the protein had also not traveled trough the latter compartment. The important role of the early secretory pathway in formation of the replication complexes was also demonstrated by the inhibition of coronaviral replication when the ER export machinery was blocked by use of the kinase inhibitor H89 or by expression of a mutant, Sar1[H79G].
Intestinal Hyperplasia Induced by Simian Virus 40 Large Tumor Antigen Requires E2F2
Authors: Sáenz-Robles M. Teresa , Markovics Jennifer A. , Chong Jean-Leon , Opavsky Rene , Whitehead Robert H. , Leone Gustavo , Pipas James M. 
Published: September 2007

ABSTRACT
The simian virus 40 large T antigen contributes to neoplastic transformation, in part, by targeting the Rb family of tumor suppressors. There are three known Rb proteins, pRb, p130, and p107, all of which block the cell cycle by preventing the transcription of genes regulated by the E2F family of transcription factors. T antigen interacts directly with Rb proteins and disrupts Rb-E2F complexes both in vitro and in cultured cells. Consequently, T antigen is thought to inhibit transcriptional repression by the Rb family proteins by disrupting their interaction with E2F proteins, thus allowing E2F-dependent transcription and the expression of cellular genes needed for entry into S phase. This model predicts that active E2F-dependent transcription is required for T-antigen-induced transformation. To test this hypothesis, we have examined the status of Rb-E2F complexes in murine enterocytes. Previous studies have shown that T antigen drives enterocytes into S phase, resulting in intestinal hyperplasia, and that the induction of enterocyte proliferation requires T-antigen binding to Rb proteins. In this paper, we show that normal growth-arrested enterocytes contain p130-E2F4 complexes and that T-antigen expression destroys these complexes, most likely by stimulating p130 degradation. Furthermore, unlike their normal counterparts, enterocytes expressing T antigen contain abundant levels of E2F2 and E2F3a. Concomitantly, T-antigen-induced intestinal proliferation is reduced in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacking E2F1. These studies support a model in which T antigen eliminates Rb-E2F repressive complexes so that specific activator E2Fs can drive S-phase entry.
Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach
Authors: Chia J K S , Chia A Y 
Published: September 2007

Background and Aims:The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated.Methods:165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV.Results:135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p⩽0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2–8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses.Conclusion:Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.
Circulating lipopolysaccharides in the blood from “bioprotein” production workers
Authors: Sikkeland L I B , Skogstad M , Øvstebø R , Brusletto B , Haug K B F , Kongerud J , Eduard W , Kierulf P 
Published: September 2007

Background:Workers producing bacterial single-cell protein (BSCP), “bioprotein,” are exposed to organic dust containing high levels of endoxins (lipopolysaccharides, LPS). Workers in this industry have complained of episodes of fever, fatigue, chest tightness, skin dryness and rubor. The aim of the present study was to quantify LPS and inflammatory mediators in plasma among the workers and non-exposed control subjects.Methods:We included eight non-smoking production workers, aged 32–51 (median 38), and eight non-smoking, non-exposed controls, aged 30–51 (median 39). Airborne and plasma endotoxin concentrations were measured, as well as plasma hsCRP and different cytokines, chemokines and metalloproteinases.Results:The workers who did not use personal respiratory protection were exposed to varying airborne levels of endotoxin, 430 (75–15 000) EU/m3 (median, range). The level of plasma LPS was significantly elevated (p = 0.01) among the workers compared to the non-exposed controls. The workers also had elevated levels of MCP-1 (p = 0.02), MIP-1α (p = 0.05) and MMP-3 (p = 0.04). IL-6 and hsCRP were also elevated among the exposed group, but not significantly (p = 0.10 and p = 0.07, respectively).Conclusions:In this study, we detected LPS in plasma of individuals exposed to high levels of LPS at their workplace. This finding is supported by elevated levels of several inflammatory cytokines among the workers, significantly exceeding that of the non-exposed control group. To the best of our knowledge, this is the first time that plasma LPS, together with increased inflammatory markers in plasma, has been detected in an occupational setting.
Time-to-pregnancy among male greenhouse workers
Authors: Bretveld R , Kik S , Hooiveld M , van Rooij I , Zielhuis G , Roeleveld N 
Published: September 2007

Objectives:Fertility problems are an increasing public health issue in industrialised countries. Exposure to exogenous agents with endocrine disrupting properties, such as some pesticides, are potential risk factors for subfertility. The aim of this study was to determine whether time-to-pregnancy (TTP) is prolonged in male greenhouse workers exposed to pesticides in comparison with a non-exposed reference group.Methods:Data were collected through self-administrated questionnaires with detailed questions on TTP, as well as on lifestyle (for example, smoking habits, coffee and alcohol consumption), work tasks, and occupational exposures of the men and their partners in the six months before conception of the most recent pregnancy. TTP was compared between male greenhouse workers (n = 694) and a non-exposed reference group (n = 613) by means of discrete proportional hazards regression analysis.Results:The crude analyses did not show a decreased overall fecundability among greenhouse workers compared to the non-exposed reference group. However, when fecundability was assessed for primigravidous couples, duogravidous couples, and multigravidous couples separately, greenhouse workers were found to be less fecund when trying to conceive their first pregnancy (FR = 0.65; 95% CI 0.46 to 0.92), which is also the most valid analysis in which pregnancy planning issues were avoided. Among couples who already experienced one or more pregnancies, no association was seen between pesticide exposure and TTP after adjustment for confounders.Conclusion:A prolonged time-to-pregnancy was observed in male greenhouse workers exposed to pesticides before conception of their first pregnancy.
CLASSIFYING LOW HEIGHT GEODESICS ON $\Gamma^3 \backslash \mathcal{H}$
Authors: SCHMIDT THOMAS A. , SHEINGORN MARK 
Published: September 2007

We show that low height-achieving non-simple geodesics on a low-index cover of the modular surface can be classified into seven types, according to the topology of highest arcs. The lowest geodesics of the signature (0;2,2,2,∞)-orbifold [Formula: see text] are the simple closed geodesics; these are indexed up to isometry by Markoff triples of positive integers (x, y, z) with x2 + y2 + z2 = 3xyz, and have heights [Formula: see text]. Geodesics considered by Crisp and Moran have heights [Formula: see text]; they conjectured that these heights, which lie in the "mysterious region" between 3 and the Hall ray, are isolated in the Markoff Spectrum. As a step in resolving this conjecture, we characterize the geometry on [Formula: see text] of geodesic arcs with heights strictly between 3 and 6. Of these, one type of geodesic arc cannot realize the height of any geodesic.
LOW HEIGHT GEODESICS ON $\Gamma^3 \backslash \mathcal{H}$: HEIGHT FORMULAS AND EXAMPLES
Authors: SCHMIDT THOMAS A. , SHEINGORN MARK 
Published: September 2007

The Markoff spectrum of binary indefinite quadratic forms can be studied in terms of heights of geodesics on low-index covers of the modular surface. The lowest geodesics on [Formula: see text] are the simple closed geodesics; these are indexed up to isometry by Markoff triples of positive integers (x, y, z) with x2 + y2 + z2 = 3xyz, and have heights [Formula: see text]. Geodesics considered by Crisp and Moran have heights [Formula: see text]; they conjectured that these heights, which lie in the "mysterious region" between 3 and the Hall ray, are isolated in the Markoff Spectrum. In our previous work, we classified the low height-achieving non-simple geodesics of [Formula: see text] into seven types according to the topology of highest arcs. Here, we obtain explicit formulas for the heights of geodesics of the first three types; the conjecture holds for approximation by closed geodesics of any of these types. Explicit examples show that each of the remaining types is realized.
Variscan events: early Palaeozoic continental rift metamorphism and late Palaeozoic crustal shortening
Authors: Weber K. 
Published: September 2007

Summary

Variscan events are interpreted in terms of a geodynamic process of long duration. It began in the early Palaeozoic, possibly in the late Precambrian in some regions, with widespread rifting of the continental lithosphere. Granulite facies metamorphism, widely in evidence in the Ordovician and Silurian, coincides in time with igneous activity and with continuous accumulation of sediment at the surface. That association is taken to indicate continental rift metamorphism above anomalous regions of the mantle. Folding and metamorphism of what is now regarded as the basement began early in the Devonian. By Upper Devonian at the latest wide areas of crystalline basement had been deeply exposed by erosion. The orogenic crustal shortening which began early in Devonian time induced intensive development of nappe tectonics involving the basement rocks. This resulted in deep-reaching crustal imbrications, especially well shown at the Moldanubian-Saxothuringian zone and Saxothuringian-Rhenohercynian zone boundaries, which evolved to carry crystalline basement rocks towards their foreland regions over distances greater than 100 km. During the course of these nappe developments folding of the adjacent sedimentary troughs proceeded. A geodynamic model of the northern flank of the central European Variscan orogen is presented. (Rb/Sr data are given using λRb
87
= 1.42 × 10
−11
y
−1
. The error limits are taken from the original papers, original data are given in brackets.)