bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD46-Utilizing Adenoviruses Inhibit C/EBPβ-Dependent Expression of Proinflammatory Cytokines
Authors: Iacobelli-Martinez Milena , Nepomuceno Ronald R. , Connolly Jodi , Nemerow Glen R. 
Published: August 2005

ABSTRACT
The majority of adenovirus serotypes utilize the coxsackievirus-adenovirus receptor (CAR) for virus-host cell attachment, but subgroup B and subgroup D (adenovirus type 37 [Ad37]) viruses recognize CD46. CD46 is a ubiquitously expressed receptor that serves as a cofactor for the inactivation of the complement components C3b and C4b, and it also serves as a receptor for diverse microbial pathogens. A reported consequence of CD46 engagement is a reduced capability of human immune cells to express interleukin-12 (IL-12), a cytokine involved in both the innate and adaptive immune responses. Studies were thus undertaken to determine whether CD46-utilizing Ads alter the expression of proinflammatory cytokines. Subgroup B (Ad16 and -35) and Ad37, but not Ad2 or -5, significantly reduced IL-12 production by human peripheral blood mononuclear cells stimulated with gamma interferon (IFN-γ) and lipopolysaccharide. IL-12 mRNA (p35 and p40 subunits) levels as well as other cytokine mRNA levels (IL-1α and -β, IL-1Ra, and IL-6) were decreased upon interaction with CD46-utilizing Ads. Analysis of transcription factor activity required for cytokine expression indicated that CD46-utilizing Ads preferentially inhibited IFN-γ-induced C/EBPβ protein expression, consequently reducing its ability to form DNA complexes. Interference with IFN-γ signaling events by CD46-utilizing Ads, but not CAR-utilizing Ads, reveals a potentially critical difference in the host immune response against distinct Ad vectors, a situation that has implications for gene delivery and vaccine development.
Variation in Interferon Sensitivity and Induction among Strains of Eastern Equine Encephalitis Virus
Authors: Aguilar Patricia V. , Paessler Slobodan , Carrara Anne-Sophie , Baron Samuel , Poast Joyce , Wang Eryu , Moncayo Abelardo C. , Anishchenko Michael , Watts Douglas , Tesh Robert B. , Weaver Scott C. 
Published: August 2005

ABSTRACT

Eastern equine encephalitis virus (EEEV) causes human encephalitis in North America (NA), but in South America (SA) it has rarely been associated with human disease, suggesting that SA strains are less virulent. To evaluate the hypothesis that this virulence difference is due to a greater ability of NA strains to evade innate immunity, we compared replication of NA and SA strains in Vero cells pretreated with interferon (IFN). Human IFN-α, -β, and -γ generally exhibited less effect on replication of NA than SA strains, supporting this hypothesis. In the murine model, no consistent difference in IFN induction was observed between NA and SA strains. After infection with most EEEV strains, higher viremia levels and shorter survival times were observed in mice deficient in IFN-α/β receptors than in wild-type mice, suggesting that IFN-α
/
β is important in controlling replication. In contrast, IFN-γ receptor-deficient mice infected with NA and SA strains had similar viremia levels and mortality rates to those of wild-type mice, suggesting that IFN-γ does not play a major role in murine protection. Mice pretreated with poly(I-C), a nonspecific IFN inducer, exhibited dose-dependent protection against fatal eastern equine encephalitis, further evidence that IFN is important in controlling disease. Overall, our in vivo results did not support the hypothesis that NA strains are more virulent in humans due to their greater ability to counteract the IFN response. However, further studies using a better model of human disease are needed to confirm the results of differential human IFN sensitivity obtained in our in vitro experiments.
Evidence that the Respiratory Syncytial Virus Polymerase Is Recruited to Nucleotides 1 to 11 at the 3′ End of the Nucleocapsid and Can Scan To Access Internal Signals
Authors: Cowton Vanessa M. , Fearns Rachel 
Published: August 2005

ABSTRACT
The 3′-terminal end of the respiratory syncytial virus genomic RNA contains a 44-nucleotide leader (Le) region adjoining the gene start signal of the first gene. Previous mapping studies demonstrated that there is a promoter located at the 3′ end of Le, which can signal initiation of antigenome synthesis. The aim of this study was to investigate the role of the 3′ terminus of the RNA template in (i) promoter recognition and (ii) determining the initiation site for antigenome synthesis. A panel of minigenomes containing additional sequence at the 3′ end of the Le were analyzed for their ability to direct antigenome and mRNA synthesis. Minigenomes containing heterologous extensions of 6 nucleotides or more were unable to support efficient RNA synthesis. However, the activity of a minigenome with a 56-nucleotide extension could be restored by insertion of Le nucleotides 1 to 11 or 1 to 13 at the 3′ end, indicating that these nucleotides, in conjunction with the 3′ terminus, are sufficient to recruit polymerase to the template. Northern blot and 5′ rapid amplification of cDNA ends analysis of antigenome RNA indicated that antigenome initiation occurred at the first position of Le, irrespective of the terminal extension. This finding demonstrates that the 3′ terminus of the RNA is not necessary for determining the antigenome initiation site. Data are presented which suggest that following recruitment to a promoter at the 3′ end of Le, the polymerase is able to scan and respond to a promoter signal embedded within the RNA template.
A Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Protein Enhances Virulence of an Attenuated Murine Coronavirus
Authors: Pewe Lecia , Zhou Haixia , Netland Jason , Tangudu Chandra , Olivares Heidi , Shi Lei , Look Dwight , Gallagher Thomas , Perlman Stanley 
Published: August 2005

ABSTRACTMost animal species that can be infected with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical disease, hindering studies of pathogenesis. To develop an alternative system for the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells, indicating that SARS-CoV proteins function in the context of a heterologous coronavirus infection. Furthermore, these results suggest that the attenuated murine coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine coronaviruses cause a reproducible and well-characterized clinical disease, offer virtually no risk to laboratory personnel, and should be useful for elucidating the role of SARS-CoV nonstructural proteins in viral replication and pathogenesis.
Human Immunodeficiency Virus Type 1 Vpr-Dependent Cell Cycle Arrest through a Mitogen-Activated Protein Kinase Signal Transduction Pathway
Authors: Yoshizuka Naoto , Yoshizuka-Chadani Yuko , Krishnan Vyjayanthi , Zeichner Steven L. 
Published: August 2005

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G
2
, which increases HIV gene expression. Some of Vpr's activities have been well described, but some functions, such as cell cycle arrest, are not yet completely characterized, although components of the ATR DNA damage repair pathway and the Cdc25C and Cdc2 cell cycle control mechanisms clearly play important roles. We investigated the mechanisms underlying Vpr-mediated cell cycle arrest by examining global cellular gene expression profiles in cell lines that inducibly express wild-type and mutant Vpr proteins. We found that Vpr expression is associated with the down-regulation of genes in the MEK2-ERK pathway and with decreased phosphorylation of the MEK2 effector protein ERK. Exogenous provision of excess MEK2 reverses the cell cycle arrest associated with Vpr, confirming the involvement of the MEK2-ERK pathway in Vpr-mediated cell cycle arrest. Vpr therefore appears to arrest the cell cycle at G
2
/M through two different mechanisms, the ATR mechanism and a newly described MEK2 mechanism. This redundancy suggests that Vpr-mediated cell cycle arrest is important for HIV replication and pathogenesis. Our findings additionally reinforce the idea that HIV can optimize the host cell environment for viral replication.
Human Cytomegalovirus IE1-72 Activates Ataxia Telangiectasia Mutated Kinase and a p53/p21-Mediated Growth Arrest Response
Authors: Castillo Jonathan P. , Frame Fiona M. , Rogoff Harry A. , Pickering Mary T. , Yurochko Andrew D. , Kowalik Timothy F. 
Published: August 2005

ABSTRACTHuman cytomegalovirus (HCMV) encodes several proteins that can modulate components of the cell cycle machinery. TheUL123gene product, IE1-72, binds the Rb-related, p107 protein and relieves its repression of E2F-responsive promoters; however, it is unable to induce quiescent cells to enter S phase in wild-type (p53+/+) cells. IE1-72 also induces p53 accumulation through an unknown mechanism. We present here evidence suggesting that IE1-72 may activate the p53 pathway by increasing the levels of p19Arfand by inducing the phosphorylation of p53 at Ser15. Phosphorylation of this residue by IE1-72 expression alone or HCMV infection is found to be dependent on the ataxia-telangiectasia mutated kinase. IE2-86 expression leads to p53 phosphorylation and may contribute to this phenotype in HCMV-infected cells. We also found that IE1-72 promotes p53 nuclear accumulation by abrogating p53 nuclear shuttling. These events result in the stimulation of p53 activity, leading to a p53- and p21-dependent inhibition of cell cycle progression from G1to S phase in cells transiently expressing IE1-72. Thus, like many of the small DNA tumor viruses, the first protein expressed upon HCMV infection activates a p53 response by the host cell.
Assembly and Intracellular Localization of the Bluetongue Virus Core Protein VP3
Authors: Kar Alak Kanti , Iwatani Nao , Roy Polly 
Published: August 2005

ABSTRACTThe bluetongue virus (BTV) core protein VP3 plays a crucial role in the virion assembly and replication process. Although the structure of the protein is well characterized, much less is known about the intracellular processing and localization of the protein in the infected host cell. In BTV-infected cells, newly synthesized viral core particles accumulate in specific locations within the host cell in structures known as virus inclusion bodies (VIBs), which are composed predominantly of the nonstructural protein NS2. However, core protein location in the absence of VIBs remains unclear. In this study, we examined VP3 location and degradation both in the absence of any other viral protein and in the presence of NS2 or the VP3 natural associate protein, VP7. To enable real-time tracking and processing of VP3 within the host cell, a fully functional enhanced green fluorescent protein (EGFP)-VP3 chimera was synthesized, and distribution of the fusion protein was monitored in different cell types using specific markers and inhibitors. In the absence of other BTV proteins, EGFP-VP3 exhibited distinct cytoplasmic focus formation. Further evidence suggested that EGFP-VP3 was targeted to the proteasome of the host cells but was dispersed throughout the cytoplasm when MG132, a specific proteasome inhibitor, was added. However, the distribution of the chimeric EGFP-VP3 protein was altered dramatically when the protein was expressed in the presence of the BTV core protein VP7, a normal partner of VP3 during BTV assembly. Interaction of EGFP-VP3 and VP7 and subsequent assembly of core-like particles was further examined by visualizing fluorescent particles and was confirmed by biochemical analysis and by electron microscopy. These data indicated the correct assembly of EGFP-VP3 subcores, suggesting that core formation could be monitored in real time. When EGFP-VP3 was expressed in BTV-infected BSR cells, the protein was not associated with proteasomes but instead was distributed within the BTV inclusion bodies, where it colocalized with NS2. These findings expand our knowledge about VP3 localization and its fate within the host cell and illustrate the assembly capability of a VP3 molecule with a large amino-terminal extension. This also opens up the possibility of application as a delivery system.
Enhancement of Enveloped Virus Entry by Phosphatidylserine
Authors: Coil David A. , Miller A. Dusty 
Published: August 2005

ABSTRACT
Enveloped virus vectors are used in a wide variety of applications. We have discovered that treatment of cultured cells with phosphatidylserine (PS) liposomes can increase virus vector infection by up to 20-fold. This effect does not abrogate virus receptor requirements, is specific to PS compared to other phospholipids, and is limited to enveloped viruses. Furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus fusion is enhanced. The liposomes are easily generated, store well, and allow enhanced infection with a variety of virus vectors and cell types.
Intracellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Absence of Nucleolar Accumulation during Infection and after Expression as a Recombinant Protein in Vero Cells
Authors: Rowland Raymond R. R. , Chauhan Vinita , Fang Ying , Pekosz Andrew , Kerrigan Maureen , Burton Miriam D. 
Published: August 2005

ABSTRACT

The nucleocapsid (N) protein of several members within the order
Nidovirales
localizes to the nucleolus during infection and after transfection of cells with N genes. However, confocal microscopy of N protein localization in Vero cells infected with the severe acute respiratory syndrome coronavirus (SARS-CoV) or transfected with the SARS-CoV N gene failed to show the presence of N in the nucleoplasm or nucleolus. Amino acids 369 to 389, which contain putative nuclear localization signal (NLS) and nucleolar localization signal motifs, failed to restore nuclear localization to an NLS-minus mutant Rev protein. These data indicate that nuclear localization is not a conserved property among all nidoviruses.
Identification of Quantitative Trait Loci for Susceptibility to Mouse Adenovirus Type 1
Authors: Welton Amanda R. , Chesler Elissa J. , Sturkie Carla , Jackson Anne U. , Hirsch Gwen N. , Spindler Katherine R. 
Published: August 2005

ABSTRACTAdult SJL/J mice are highly susceptible to mouse adenovirus type 1 (MAV-1) infections, whereas other inbred strains, including BALB/cJ, are resistant (K. R. Spindler, L. Fang, M. L. Moore, C. C. Brown, G. N. Hirsch, and A. K. Kajon, J. Virol.75:12039-12046, 2001). Using congenic mouse strains, we showed that theH-2shaplotype of SJL/J mice is not associated with susceptibility to MAV-1. Susceptibility of MAV-1-infected (BALB/cJ × SJL/J)F1mice was intermediate between that of SJL/J mice and that of BALB/cJ mice, indicating that susceptibility is a genetically controlled quantitative trait. We mapped genetic loci involved in mouse susceptibility to MAV-1 by analysis of 192 backcross progeny in a genome scan with 65 simple sequence length polymorphic markers. A major quantitative trait locus (QTL) was detected on chromosome 15 (Chr 15) with a highly significant logarithm of odds score of 21. The locus on Chr 15 alone accounts for 40% of the total trait variance between susceptible and resistant strains. QTL modeling of the data indicated that there are a number of other QTLs with small effects that together with the major QTL on Chr 15 account for 54% of the trait variance. Identification of the major QTL is the first step in characterizing host genes involved in susceptibility to MAV-1.
A Single Amino Acid Substitution in 1918 Influenza Virus Hemagglutinin Changes Receptor Binding Specificity
Authors: Glaser Laurel , Stevens James , Zamarin Dmitriy , Wilson Ian A. , García-Sastre Adolfo , Tumpey Terrence M. , Basler Christopher F. , Taubenberger Jeffery K. , Palese Peter 
Published: August 2005

ABSTRACT
The receptor binding specificity of influenza viruses may be important for host restriction of human and avian viruses. Here, we show that the hemagglutinin (HA) of the virus that caused the 1918 influenza pandemic has strain-specific differences in its receptor binding specificity. The A/South Carolina/1/18 HA preferentially binds the α2,6 sialic acid (human) cellular receptor, whereas the A/New York/1/18 HA, which differs by only one amino acid, binds both the α2,6 and the α2,3 sialic acid (avian) cellular receptors. Compared to the conserved consensus sequence in the receptor binding site of avian HAs, only a single amino acid at position 190 was changed in the A/New York/1/18 HA. Mutation of this single amino acid back to the avian consensus resulted in a preference for the avian receptor.
Relative Contributions of Measles Virus Hemagglutinin- and Fusion Protein-Specific Serum Antibodies to Virus Neutralization
Authors: de Swart Rik L. , Yüksel Selma , Osterhaus Albert D. M. E. 
Published: August 2005

ABSTRACT
The relative contribution of measles virus hemagglutinin (H)- or fusion protein (F)-specific antibodies to virus neutralization (VN) has not been demonstrated. We have depleted these specific antibodies from sera collected from young adults, who had been vaccinated during childhood, by prolonged incubation with viable transfected human melanoma cells expressing H or F. Simultaneous depletion of antibodies of both specificities completely abrogated VN activity. Depletion of F-specific antibodies only had a minimal effect, whereas removal of H-specific antibodies resulted in almost complete reduction of VN activity. These results demonstrate that measles virus neutralizing antibodies are mainly directed to the H protein.
VISCOSITY METHOD FOR THE DETERMINATION OF THE THICKNESS OF SOLVATION LAYERS NEAR PARTICLES DISPERSED IN A LIQUID
Authors: SONG SHAOXIAN , ZHANG YIMIN , FORT TOMLINSON 
Published: August 2005

In this paper, we present a method for determining the thickness of solvation layers near spherical particles dispersed in a liquid through measurements of the viscosity of the dispersion as a function of the volume fraction of the dry particles in the dispersion and the size distribution of the particles. It is termed viscosity method. The theoretical derivation for the method is based on Einstein's theory of viscosity of dispersions, while two assumptions are made: 1. Solvation layers contribute to increasing the viscosity of the dispersion in c times as the same volume of rigid solid spheres. 2. The thickness of solvation layers is the same near every chemically similar spherical particle in a given dispersion.
The Development of Doctrine: A Lutheran Understanding and its Ecumenical Application
Authors: Root Michael 
Published: August 2005

AbstractIn this essay, a Lutheran understanding of the development of doctrine is developed, in contrast with what George Lindbeck calls ‘historical situationalism’, the limitations of which are analysed. While the final authority of doctrine is a function of its evangelical content, a particular historical development of church teaching can possess a subordinate, distinct, formal authority as an authoritative sign of the material authority of its content. Such developments of doctrine can be irreversible. This understanding is placed in relation to the most prominent doctrine on the development of doctrine, the Catholic teaching on papal infallibility. The comprehensive narrative of the Western church’s struggle over authority since the late Middle Ages should be seen as including both Catholic and non-Catholic developments and as still unresolved.
The Common Statement Called into Question
Authors: Wagschal David 
Published: August 2005

AbstractThe forms, structures and conventions of ecumenical texts, and the methods of their production, play a determinative role in shaping the successes and failures of the quest for Christian unity. The textual genre of the ‘common statement’ has played a particular critical role in the development of the modern ecumenical movement, but hermeneutical problems inherent in this genre demand a re-evaluation of the viability of these texts as effective vehicles for ecumenical dialogue. The re-imagination of ecumenism for the twenty-first century must begin with a reassessment of the role of this traditional text form as part of a broader re-imagination of the entire textual life of the movement.
What is Communion and When is it Full?
Authors: Small Joseph 
Published: August 2005

Abstract‘Full communion’ has become the favoured term to characterize forms of reconciled life between and among churches in North America. Yet the term is problematic. This article examines ‘full communion’ in light of its genesis in the ecumenical movement, challenges from Orthodox and Roman Catholic perspectives, the biblical witness, and the actual life of churches that are in ‘full communion’. The article concludes by suggesting a way to retain and employ koinoō nia categories in ecumenical relations.
Whose History? Historical Method and Ecclesiology in Ecumenical Context
Authors: Morris Jeremy 
Published: August 2005

AbstractThis article explores the concealed relationship of changing historical formulations of Christian doctrine to the statements of doctrine contained in ecumenical dialogue reports, and argues for a form of church history that would be ecumenically and theologically useful. Through a series of specific examples, it points to the hidden history of the ecclesiological contexts in which doctrine is situated. Noting limitations in the concept of ‘paradigm shift’, as well as in theories of doctrinal development, it argues that church history needs to attend to three levels of historical argumentation, covering doctrines, institutions, and social context, and proposes a historical methodology cognizant of all three, and above all of the links between all three.