bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between the Cytoplasmic Domain of ICAM-1 and Pr55
Gag
Leads to Acquisition of Host ICAM-1 by Human Immunodeficiency Virus Type 1
Authors: Beauséjour Yannick , Tremblay Michel J. 
Published: October 2004

ABSTRACT

We have examined the molecular basis for the selective incorporation of the adhesion molecule ICAM-1 within human immunodeficiency virus type 1 (HIV-1). The process of ICAM-1 incorporation was investigated by using different ICAM-1 constructs in combination with virus capture and immunoprecipitation studies, Western blot and confocal microscopy analyses, and infectivity assays. Experiments conducted with viruses bearing a truncated version of ICAM-1 revealed that the cytoplasmic domain of ICAM-1 governs insertion of this adhesion molecule into HIV-1. Further experiments suggested that there is an association between ICAM-1 and the virus-encoded Pr55
Gag
polyprotein. This study represents the first demonstration that structural Gag polyproteins play a key role in the uptake of a host-derived cell surface by the virus entity. Taken together, our results indicate that interactions between viral and cellular proteins are responsible for the selective uptake of host ICAM-1 by HIV-1. This observation describes a new strategy by which HIV-1 can modulate its replicative cycle, considering that insertion of ICAM-1 within nascent virions has been shown to increase virus infectivity.
Activation of Transcription Factor Nrf-2 and Its Downstream Targets in Response to Moloney Murine Leukemia Virusts1-Induced Thiol Depletion and Oxidative Stress in Astrocytes
Authors: Qiang Wenan , Cahill Jodi M. , Liu Jinrong , Kuang Xianghong , Liu Na , Scofield Virginia L. , Voorhees Jennifer R. , Reid Amy J. , Yan Mingshan , Lynn William S. , Wong Paul K. Y. 
Published: October 2004

ABSTRACTThe neuroimmunodegenerative syndrome that develops in mice infected withts1, a mutant of Moloney murine leukemia virus, resembles human AIDS. Bothts1 and human immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes but do not infect neurons. Oxidative stress has been implicated in the neuropathology of AIDS dementia and other neurodegenerative diseases. We report here thatts1 infection of astrocytes (both transformed C1 cells and primary cultures) also induces thiol (i.e., glutathione and cysteine) depletion and reactive oxygen species (ROS) accumulation, events occurring in parallel with viral envelope precursor gPr80envaccumulation and upregulated expression of endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore,ts1-infected astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf-2 transcription factor, as well its targets, the xCT cystine/glutamate antiporter, γ-glutamylcysteine ligase, and glutathione peroxidase. Depleting intracellular thiols by treating uninfected astrocytes with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine-deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in astrocytes specifically increases expression of the above thiol synthesis-related proteins. Further treatment with BSO orN-acetylcysteine in transfected cells modulates this expression. Thiol depletion also accelerates cell death, while thiol supplementation promotes survival ofts1-infected cells. Together, our results indicate thatts1 infection of astrocytes, along withts1-induced gPr80envaccumulation, endoplasmic reticulum stress, thiol depletion, and oxidative stress, accelerates cell death; in response to the thiol depletion and oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant defenses, promoting cell survival.
Early Stage of Establishment of Persistent Sendai Virus Infection: Unstable Dynamic Phase and Then Selection of Viruses Which Are Tightly Cell Associated, Temperature Sensitive, and Capable of Establishing Persistent Infection
Authors: Ito Morihiro , Takeuchi Taijiro , Nishio Machiko , Kawano Mitsuo , Komada Hiroshi , Tsurudome Masato , Ito Yasuhiko 
Published: October 2004

ABSTRACT
We obtained 157 cloned cell lines persistently infected with Sendai virus; these cell lines were generated independently of each other. Infectious viruses could be isolated from 123 of these cloned cell lines by inoculation of culture fluids or infected cells into embryonated eggs. The majority of the viruses carried by cells persistently infected with viruses showed high cytotoxicity and did not have the ability to establish persistent infection. The association of carried virus with cells became stronger and virus isolation correspondingly became more difficult as cells persistently infected with virus were subcultured. Viruses derived from virus-infected cells eventually acquired the ability to establish persistent infection, although the ways in which the viruses acquired this ability varied. The viruses also acquired temperature sensitivity as persistently infected cells were subcultured. First, the hemagglutinin-neuraminidase and M proteins acquired temperature sensitivity, and then the polymerase(s) did so. The M proteins were localized in the nuclei of cells infected with cloned viruses that had the ability to establish persistent infection. Cells infected with viruses capable of establishing persistent infection showed no or slight staining by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. Specific amino acid substitutions accumulated in the M protein and the L protein as virus-infected cells were subcultured. This study shows that there is an unstable dynamic phase at an early stage of the establishment of persistent Sendai virus infection (steady state), and then viruses capable of establishing persistent infection are selected.
Identification of a Negative Regulatory Element in the Epstein-Barr Virus Zta Transactivation Domain That Is Regulated by the Cell Cycle Control Factors c-Myc and E2F1
Authors: Lin Zhen , Yin Qinyan , Flemington Erik 
Published: October 2004

ABSTRACT

Reactivation in Epstein-Barr virus (EBV) is closely associated with a G
0
/G
1
cell cycle arrest which can be induced either by lytic cycle-inducing agents or by the immediate-early gene product Zta. Accumulating evidence shows that in epithelial cells, downregulation of the proto-oncogene, c-
myc
, plays an important role in lytic cycle-associated cell growth arrest. Here, we provide evidence that c-Myc provides a gatekeeper function to ensure that certain cell cycle inhibitory events have been capitulated prior to full progression into the lytic cycle. Specifically, we show that reconstitution of c-Myc expression during the lytic cycle to levels observed in cycling uninduced cells inhibits the transactivation function of Zta. Nuclear localization studies show that c-Myc does not grossly alter the nuclear localization of Zta or its association with the insoluble nuclear fraction. Enforced expression of another transcription factor that promotes cell cycle progression, E2F1, also inhibits Zta transactivation. Analysis of c-Myc- and E2F1-mediated inhibition of a panel of Zta mutants shows parallel genetics and inhibition maps to a small bipartite sequence located between amino acids 29 and 53 of Zta, containing homology to the proline-rich domain of the tumor suppressor protein p53. Mutation of a conserved tryptophan residue located at amino acid 49 of Zta largely prevents inhibition by both c-Myc and E2F1. These studies identify a negative regulatory element within the Zta activation domain that is regulated by the cell cycle-promoting factors c-Myc and E2F1.
Structural and Thermodynamic Basis for the Binding of TMC114, a Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor
Authors: King Nancy M. , Prabu-Jeyabalan Moses , Nalivaika Ellen A. , Wigerinck Piet , de Béthune Marie-Pierre , Schiffer Celia A. 
Published: October 2004

ABSTRACT

TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the basis for this potency, we solved crystal structures of TMC114 complexed with wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V) protease variant. In addition, we determined the corresponding binding thermodynamics by isothermal titration calorimetry. TMC114 binds approximately 2 orders of magnitude more tightly to the wt enzyme (

K
d

= 4.5 × 10
−12
M) than APV (

K
d

= 3.9 × 10
−10
M). Our X-ray data (resolution ranging from 2.2 to 1.2 Å) reveal strong interactions between the
bis
-tetrahydrofuranyl urethane moiety of TMC114 and main-chain atoms of D29 and D30. These interactions appear largely responsible for TMC114's very favorable binding enthalpy to the wt protease (−12.1 kcal/mol). However, TMC114 binding to the MDR HIV-1 protease is reduced by a factor of 13.3, whereas the APV binding constant is reduced only by a factor of 5.1. However, even with the reduction in binding affinity to the MDR HIV protease, TMC114 still binds with an affinity that is more than 1.5 orders of magnitude tighter than the first-generation inhibitors. Both APV and TMC114 fit predominantly within the substrate envelope, a property that may be associated with decreased susceptibility to drug-resistant mutations relative to that of first-generation inhibitors. Overall, TMC114's potency against MDR viruses is likely a combination of its extremely high affinity and close fit within the substrate envelope.
Functional Correlation of P-Glycoprotein Expression and Genotype with Expression of the Human Immunodeficiency Virus Type 1 Coreceptor CXCR4
Authors: Owen Andrew , Chandler Becky , Bray Patrick G. , Ward Stephen A. , Hart C. Anthony , Back David J. , Khoo Saye H. 
Published: October 2004

ABSTRACTThe aim of this study was to investigate the relationship between lymphocyte P-glycoprotein (P-gp) expression and genotype in vivo and the expression of lymphocyte receptors critical in the life cycle of human immunodeficiency virus type 1 (HIV-1), i.e., CD4, CCR5, and CXCR4. Using flow cytometry to quantify each membrane receptor/transporter, we demonstrate a highly significant correlation between P-gp protein expression and the expression of CXCR4 (rho = 0.874;P< 0.0001). Furthermore, confocal microscopy showed colocalized expression of CXCR4 and P-gp in the lymphocyte membrane. This significant relationship was also apparent at the mRNA level by use of reverse transcription-PCR (rho = 0.61;P< 0.005) and was present in both phytohemagglutinin-stimulated and unstimulated peripheral blood mononuclear cells. Genotypic analysis of the C3435T single-nucleotide polymorphism of P-gp confirmed significantly higher levels of P-gp in C (range, 2.45 to 11.00 relative fluorescence units [RFU])- than in T (range, 0.25 to 5.00 RFU)-homozygous individuals (P= 0.0088; 95% confidence interval [95% CI], 0.7 to 6.3 RFU). An equivalent association between CXCR4 levels and C (range, 12.7 to 44.1 RFU) versus T (range, 3 to 18.9 RFU) genotype was also demonstrated (P= 0.0019; 95% CI, 5.4 to 23.7). Functionally, although these correlates had no impact on HIV-1 production from either X4- or R5-tropic virus, expression correlated significantly with the activity of the HIV-1 protease inhibitor (PI) saquinavir for both P-gp (rho = 0.75;P= 0.0019) and CXCR4 (rho = 0.71;P= 0.0041). This study defines an association between P-gp (expression and genotype) and CXCR4 that may have implications for the selection of viral tropism and the access of drugs to protease for specific tropic types. The interplay between these two proteins may also influence the viral genotypes which escape effective chemotherapy and which therefore have the opportunity to evolve resistance to PIs.
Hepatitis C Virus Core Protein Associates with Detergent-Resistant Membranes Distinct from Classical Plasma Membrane Rafts
Authors: Matto Meirav , Rice Charles M. , Aroeti Benjamin , Glenn Jeffrey S. 
Published: October 2004

ABSTRACT
A subpopulation of hepatitis C virus (HCV) core protein in cells harboring full-length HCV replicons is biochemically associated with detergent-resistant membranes (DRMs) in a manner similar to that of markers of classical lipid rafts. Core protein does not, however, colocalize in immunofluorescence studies with classical plasma membrane raft markers, such as caveolin-1 and the B subunit of cholera toxin, suggesting that core protein is bound to cytoplasmic raft microdomains distinct from caveolin-based rafts. Furthermore, while both the structural core protein and the nonstructural protein NS5A associate with membranes, they do not colocalize in the DRMs. Finally, the ability of core protein to localize to the DRMs did not require other elements of the HCV polyprotein. These results may have broad implications for the HCV life cycle and suggest that the HCV core may be a valuable probe for host cell biology.
Statin Compounds Reduce Human Immunodeficiency Virus Type 1 Replication by Preventing the Interaction between Virion-Associated Host Intercellular Adhesion Molecule 1 and Its Natural Cell Surface Ligand LFA-1
Authors: Giguère Jean-François , Tremblay Michel J. 
Published: October 2004

ABSTRACT
A variety of host factors, including membrane proteins acquired by human immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption onto host cells. Examples include the integrin intercellular adhesion molecule 1 (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based on the idea that these compounds have been shown to block ICAM-1-LFA-1 interactions. Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection.
Low Level of Lytic Replication in a Recombinant Epstein-Barr Virus Carrying an Origin of Replication Devoid of BZLF1-Binding Sites
Authors: Feederle R. , Delecluse H. J. 
Published: October 2004

ABSTRACT

Binding of the BZLF1 viral transactivator to Epstein-Barr virus (EBV)
oriLyt
has been reported to be essential for viral DNA replication. We have constructed a recombinant virus (E2-
oriLyt-
R) in which the
oriLyt
BZLF1-binding sites (ZRE) were exchanged against papilloma E2-binding sites. A fusion protein between the BZLF1 protein-transactivating domain and the E2 protein-binding domain was able to reactivate lytic replication in E2-
oriLyt-
R. However, BZLF1 alone could also induce E2-
oriLyt-
R, albeit with much lower efficiency. ZRE are therefore important but not absolutely essential
cis
elements for lytic replication. This shows the importance of recombinants to evaluate viral functions.
Genetic Interactions between Hepatitis C Virus Replicons
Authors: Evans Matthew J. , Rice Charles M. , Goff Stephen P. 
Published: October 2004

ABSTRACT
To investigate interactions between hepatitis C virus (HCV) RNA replication complexes, a system was developed to simultaneously select different HCV subgenomic replicons within the same cell. Transcomplementation of defective replicons was not observed, suggesting an isolated and independent nature of the HCV RNA replication complex. In contrast, a high level of competition between replicons was observed, such that the presence and increased fitness of one replicon reduced the capacity of a second one to stably replicate. These results suggest that at least one factor in Huh7 cells required for HCV RNA replication is limiting and saturable.
DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus
Authors: Marzi Andrea , Gramberg Thomas , Simmons Graham , Möller Peggy , Rennekamp Andrew J. , Krumbiegel Mandy , Geier Martina , Eisemann Jutta , Turza Nadine , Saunier Bertrand , Steinkasserer Alexander , Becker Stephan , Bates Paul , Hofmann Heike , Pöhlmann Stefan 
Published: October 2004

ABSTRACTThe lectins DC-SIGN and DC-SIGNR can augment viral infection; however, the range of pathogens interacting with these attachment factors is incompletely defined. Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. SIGNR1, a murine DC-SIGN homologue, also enhanced infection driven by MARV and Ebola virus GP and could be targeted to assess the role of attachment factors in filovirus infection in vivo.
${\rm C}^+_{60}$ IONS IN COLLISIONS WITH CRYSTALLINE SURFACES: KINEMATICS AND DYNAMICS
Authors: LILL TH. , BUSMANN H.-G. , LACHER F. , HERTEL I.V. 
Published: October 2004

Collisions of [Formula: see text] ions with surfaces of highly oriented pyrolytic graphite (HOPG), diamond (111) and heteroepitaxial fullerite films on mica in the impact energy range between 100 and 1500 eV are studied by mass, energy, and angle resolved time-of-flight mass spectrometry. For the graphite and diamond surfaces, highly inelastic scattering has been observed. The analysis of the velocity dependence of the scattered ions reveals that the normal and tangential component of the ion velocity have different significance for the collision dynamics. The normal component of the velocity appears to determine the amount of energy transferred into vibrational and deformational energy of the projectile and target. The final kinetic energy is independent of the impact energy for impact angles of ≈20° and impact energies between 140 and 450 eV. This observation can be explained by the existence of an upper bound of the final kinetic energy that is defined by the amount of energy stored in the deformed molecule without being deposited or destroyed. The tangential component is partially transformed into rotational energy of the [Formula: see text] in the collision with the surface, as may be explained by a simple rolling ball model. In contrast, scattering from heteroepitaxial fullerite films is nearly elastic for impact energies up to 230 eV and impact angles of about 20°. Additionally, the velocity distributions reveal a low velocity component. Its relative intensity increases with increasing impact energy and remains the only feature in the velocity distribution for impact energies higher than 290 eV. This component is due to sputtering of surface molecules. The angular dependent intensities of the fast ions exhibit a rich structure. This can be attributed to rainbow scattering, as confirmed by classical trajectory and molecular dynamics calculations with different levels of sophistication. These calculations also show that linear collision sequences along the closed packed rows of the fullerite surface may be generated as the result of the [Formula: see text] impact. A detailed study of these collision sequences by molecular dynamics calculations reveals that rainbow effects might be possible when these sequences are defocused due to thermal motion of the surface molecules. The contribution of this process to the measured velocity and angular distributions is discussed.
NEW DEVELOPMENTS AND CLASSICAL THEORIES OF TURBULENCE
Authors: LEVICH E. 
Published: October 2004

In this paper we review certain classical and modern concepts pertinent for the theory of developed turbulent flows. We begin by introducing basic facts concerning the properties of the Navier-Stokes equation with the emphasis on invariant properties of the vorticity field. Then we discuss classical semiempirical approaches to developed turbulence which for a long time have constituted a basis for engineering solutions of turbulent flows problems. We do it for two examples, homogeneous isotropic turbulence and flat channel turbulent flow. Next we discuss the insufficiency of classical semi-empirical approaches. We show that intermittency is an intrinsic feature of all turbulent flows and hence it should be accounted for in any reasonable theoretical approach to turbulence. We argue that intermittency in physical space is in one to one correspondence with certain phase coherence of turbulence in an appropriate dual space, e.g. Fourier space for the case of homogeneous isotropic turbulence. In the same time the phase coherence has its origin in invariant topological properties of vortex lines in inviscid flows, modified by the presence of small molecular viscosity. This viewpoint is expounded again using the examples of homogeneous isotropic turbulence and channel flow turbulence. Finally we briefly discuss the significance of phase coherence and intermittency in turbulence for the fundamental engineering challenge of turbulence control.
A COMPARISON OF THE PERFORMANCE OF ER FLUIDS IN SQUEEZE
Authors: Sproston J L , Wahed A K El , Williams E W , Stanway R 
Published: October 2004

This paper is concerned with an experimental and theoretical study of the characteristics of two ER fluids and their application to vibration control when used in squeeze flow. It is seen that when the fluids are sandwiched between two electrodes, the lower one oscillating and the upper one fixed, displacement control of the lower electrode can be achieved by control of the applied field. Of particular interest is the dependence of the force transmitted across the fluids on oscillation frequency and applied field. A time-dependent theoretical model is seen to satisfactorily predict the device performance when allowance is made for a non-linear dependence of the post-yield shear stress on shear rate.
Transfer Function Identification of an Electro-Rheological Actuator
Authors: Brookfield D.J. , Dlodlo Z.B. 
Published: October 2004

A fluid clutch utilising an Electro-Rheological (ER) suspension provides a controlled torque coupling between input and output through the control of the applied electric field. If the input is driven at constant speed the device can be considered as an ER torque actuator and thus be used to drive robot links or other mechanisms requiring precise positioning. Such an ER torque actuator can replace a DC servo-motor in robotic applications with the benefits of low time constant and smooth output torque unaffected by cogging (i.e. variation in torque of a DC motor as the magnetic reluctance of the armature-stator path changes with rotation). Although the ER actuator has many benefits, it suffers from a non-linear and time varying relationship between input voltage and output torque. These undesirable characteristics can be mitigated by providing a local closed loop controller around the system. The design of such a controller requires a knowledge of the relationship between the applied voltage and output torque; i.e. the transfer function of the actuator. This transfer function has been determined by observing the response of an ER torque actuator in the frequency domain. It is shown that a linear transfer function model reasonable represents the actuator behaviour, that the actuator is a stable second order system and that the time constant of the clutch studied is sufficiently short to hold considerable promise for robotic applications. Furthermore, the maximum torque capability is shown to be sufficient for many medium scale industrial robots.