bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Determinants of Chemokine Binding by an Ectromelia Virus-Encoded Decoy Receptor
Authors: Arnold Phoebe L. , Fremont Daved H. 
Published: July 2006

ABSTRACTThe EVM1 protein encoded byEctromelia virusis a member of a highly conserved family of poxvirus chemokine binding proteins that interfere with host immune surveillance processes. EVM1 is abundantly expressed early during mousepox infection and is able to selectively bind CC chemokines and inhibit their interactions with host receptors. Here, we characterize the interaction between EVM1 and the human and murine chemokines CCL3 (MIP-1α), CCL2 (MCP-1), and CCL5 (RANTES). Each of these CC chemokines binds EVM1 with 1:1 stoichiometry and equilibrium dissociation constants ranging from 29 pM to 20 nM. The interactions are characterized by rapid-association kinetics between acidic EVM1 and generally basic chemokines with half-lives enduring up to 30 min. The 2.6-Å crystal structure of EVM1 reveals a globular β sandwich with a large, sequence-conserved surface patch encircled by acidic residues on one face of the protein. To determine whether this conserved cluster of residues is involved in chemokine engagement, a structure-based mutational analysis of EVM1 was employed. Mapping of the mutational results onto the surface of EVM1 reveals that a cluster of five residues (I173, S171, S134, N136, and Y69) emanating from one β sheet is critical for CCL2 and CCL3 sequestration. Additionally, we find that the extended β2-β4 loop flanking this conserved cluster is also essential for high-affinity, lasting interactions with chemokines. This analysis provides insight into the mechanism of CC-chemokine inhibition employed by the poxvirus family of chemokine decoy receptors.
Genomic Sites of Human Immunodeficiency Virus Type 2 (HIV-2) Integration: Similarities to HIV-1 In Vitro and Possible Differences In Vivo
Authors: MacNeil Adam , Sankalé Jean-Louis , Meloni Seema Thakore , Sarr Abdoulaye Dieng , Mboup Souleymane , Kanki Phyllis 
Published: July 2006

ABSTRACT
Retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (HIV-1) integration strongly favoring transcriptional units. Additionally, studies with HIV-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. HIV-2 is less pathogenic than HIV-1 and is believed to have a lower replication rate in vivo. Although differences in integration site selection between HIV-2 and HIV-1 could potentially explain the attenuated pathogenicity of HIV-2, no studies have characterized integration site selection by HIV-2. In this study, we mapped 202 HIV-2 integration sites during in vitro infection of peripheral blood mononuclear cells with a primary HIV-2 isolate. In addition, we assayed for in vivo proviral integration within heterochromatin in 21 HIV-1-infected subjects and 23 HIV-2-infected subjects, using an alphoid repeat PCR assay. During in vitro infection, HIV-2 displayed integration site preferences similar to those previously reported for HIV-1. Notably, 82% of HIV-2 integrations mapped to Refseq genes, and integration strongly favored regions of the genome with high gene density and high GC content. Though rare, the proportion of HIV-2 subjects with evidence of proviral integration within heterochromatin in vivo was higher than that of HIV-1-infected subjects. It is therefore possible that integration site selection may play a role in the differences in HIV-1 and HIV-2 in vivo pathogenesis.
Ancient Origin and Molecular Features of the Novel Human T-Lymphotropic Virus Type 3 Revealed by Complete Genome Analysis
Authors: Switzer William M. , Qari Shoukat H. , Wolfe Nathan D. , Burke Donald S. , Folks Thomas M. , Heneine Walid 
Published: July 2006

ABSTRACT
Human T-lymphotropic virus type 3 (HTLV-3) is a new virus recently identified in two primate hunters in Central Africa. Limited sequence analysis shows that HTLV-3 is distinct from HTLV-1 and HTLV-2 but is genetically similar to simian T-lymphotropic virus type 3 (STLV-3). We report here the first complete HTLV-3 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocytes from an HTLV-3-infected person. The HTLV-3(2026ND) genome is 8,917 bp long and is genetically equidistant from HTLV-1 and HTLV-2, sharing about 62% identity. Phylogenetic analysis of all gene regions confirms this relationship and shows that HTLV-3 falls within the diversity of STLV-3, suggesting a primate origin. However, HTLV-3(2026ND) is unique, sharing only 87% to 92% sequence identity with STLV-3. SimPlot and phylogenetic analysis did not reveal any evidence of genetic recombination with either HTLV-1, HTLV-2, or STLV-3. Molecular dating estimates that the ancestor of HTLV-3 is as old as HTLV-1 and HTLV-2, with an inferred divergence time of 36,087 to 54,067 years ago. HTLV-3 has a prototypic genomic structure, with all enzymatic, regulatory, and structural proteins preserved. Like STLV-3, HTLV-3 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains a unique activator protein-1 transcription factor upstream of the 21-bp repeat elements. A PDZ motif, like that in HTLV-1, which is important for cellular signal transduction and transformation, is present in the C terminus of the HTLV-3 Tax protein. A basic leucine zipper region located in the antisense strand of HTLV-1, believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-3. The ancient origin of HTLV-3, the broad distribution of STLV-3 in Africa, and the propensity of STLVs to cross species into humans all suggest that HTLV-3 may be prevalent and support the need for expanded surveillance for this virus.
Prevalence and Genetic Diversity of Coronaviruses in Bats from China
Authors: Tang X. C. , Zhang J. X. , Zhang S. Y. , Wang P. , Fan X. H. , Li L. F. , Li G. , Dong B. Q. , Liu W. , Cheung C. L. , Xu K. M. , Song W. J. , Vijaykrishna D. , Poon L. L. M. , Peiris J. S. M. , Smith G. J. D. , Chen H. , Guan Y. 
Published: July 2006

ABSTRACT
Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.
Mapping the Domains of CD134 as a Functional Receptor for Feline Immunodeficiency Virus
Authors: Willett Brian J. , McMonagle Elizabeth L. , Bonci Francesca , Pistello Mauro , Hosie Margaret J. 
Published: July 2006

ABSTRACT

The feline homologue of CD134 is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4
+
helper T cells. However, strains of FIV differ in utilization of CD134; the prototypic strain PPR requires a minimal determinant in the first cysteine-rich domain (CRD1) of feline CD134 to confer near-optimal receptor function, while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; the amino acid substitutions S78N-S79Y-K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134, with tyrosine-79 appearing to be the critical residue for restoration of receptor function.
Cytomegalovirus Encodes a Positive Regulator of Antigen Presentation
Authors: Holtappels Rafaela , Gillert-Marien Dorothea , Thomas Doris , Podlech Jürgen , Deegen Petra , Herter Sylvia , Oehrlein-Karpi Silke A. , Strand Dennis , Wagner Markus , Reddehase Matthias J. 
Published: July 2006

ABSTRACT

Murine cytomegalovirus encodes three regulators of antigen presentation to antiviral CD8 T cells. According to current paradigms, all three regulators are committed to the inhibition of the presentation of antigenic peptides. Whereas m152/gp40 catalyzes the retention of peptide-loaded major histocompatibility complex (MHC) class I molecules in a
cis
-Golgi compartment, m06/gp48 binds stably to class I molecules and directs them into the cellular cargo-sorting pathway of lysosomal degradation. Regulator m04/gp34 also binds stably to class I molecules, but unlike m152 and m06, it does not downmodulate MHC class I cell surface expression. It has entered the literature as a direct inhibitor of T-cell recognition of the MHC-peptide complex at the cell surface. In this work, we have studied the presentation of antigenic viral peptides in cells infected with a comprehensive set of mutant viruses expressing the three regulators separately as well as in all possible combinations. The results redefine m04 as a positive regulator dedicated to the facilitation of antigen presentation. When expressed alone, it did not inhibit T-cell recognition, and when expressed in the presence of m152, it restored antigen presentation by antagonizing the inhibitory function of m152. Its intrinsic positive function, however, was antagonized and even slightly overcompensated for by the negative regulator m06. In an adoptive cell transfer model, the opposing forces of the three regulators were found to govern immune surveillance in the infected host. While negative regulators, also known as immunoevasins, are common, the existence of a positive regulator is without precedent and indicates an intriguing genetic potential of this virus to influence antigen presentation.
Human Cytomegalovirus Subverts the Functions of Monocytes, Impairing Chemokine-Mediated Migration and Leukocyte Recruitment
Authors: Frascaroli Giada , Varani Stefania , Moepps Barbara , Sinzger Christian , Landini Maria Paola , Mertens Thomas 
Published: July 2006

ABSTRACTDespite their role in innate and adaptive immunity, during human cytomegalovirus (HCMV) infection, monocytes are considered to be an important target of infection, a site of latency, and vehicles for virus dissemination. Since chemokine receptors play crucial roles in monocyte activation and trafficking, we investigated the effects of HCMV on their expression and function. By using endotheliotropic strains of HCMV, we obtained high rates (roughly 50%) of in vitro-infected monocytes but only restricted viral gene expression. At 24 h after infection, while the chemokine receptors CX3CR and CCR7 were unaffected, CCR1, CCR2, CCR5, and CXCR4 were downmodulated on the cell surface and retained intracellularly. Structural components of the viral particles, but not viral gene expression or soluble factors released from infected cells, accounted for the changed localization of the receptor molecules and for the block of chemokine-driven migration. HCMV-infected monocytes indeed became unresponsive to inflammatory and homeostatic chemokines, although the basal cell motility and responsiveness toN-formyl-Met-Leu-Phe were unaffected or slightly increased. The production of inflammatory mediators responsible for the recruitment of other immune cells was also hampered by HCMV. Whereas endothelial and fibroblast cells infected by HCMV efficiently recruited leukocytes, infected monocytes were unable to recruit lymphocytes, monocytes, and neutrophils. Our data further highlight the complex level of interference exerted by HCMV on the host immune system.
Cyclosporine Increases Human Immunodeficiency Virus Type 1 Vector Transduction of Primary Mouse Cells
Authors: Noser Josh A. , Towers Greg J. , Sakuma Ryuta , Dumont Jean-Maurice , Collins Mary K. L. , Ikeda Yasuhiro 
Published: July 2006

ABSTRACT
Murine primary cells are poorly permissive to human immunodeficiency virus type 1 (HIV-1) vector infection. Retroviral infectivity is influenced by dominant inhibitors such as TRIM5α. Sensitivity to TRIM5α is altered by interactions between cyclophilin A and the HIV-1 capsid. Here we demonstrate that competitive inhibitors of cyclophilins, cyclosporine or the related Debio-025, stimulate HIV-1 vector transduction of primary murine cells, including bone marrow and macrophages, up to 20-fold. Unexpectedly, the infectivity of an HIV-1 mutant or a simian lentivirus that does not recruit cyclophilin A is also stimulated by these drugs. We propose that cyclosporine and related compounds will be useful tools for experimental infection of murine primary cells. It is possible that HIV-1 infection of murine cells is inhibited by dominant factors related to immunophilins.
Influenza Virus Receptor Specificity and Cell Tropism in Mouse and Human Airway Epithelial Cells
Authors: Ibricevic Aida , Pekosz Andrew , Walter Michael J. , Newby Celeste , Battaile John T. , Brown Earl G. , Holtzman Michael J. , Brody Steven L. 
Published: July 2006

ABSTRACT
Recent human infections caused by the highly pathogenic avian influenza virus H5N1 strains emphasize an urgent need for assessment of factors that allow viral transmission, replication, and intra-airway spread. Important determinants for virus infection are epithelial cell receptors identified as glycans terminated by an α2,3-linked sialic acid (SA) that preferentially bind avian strains and glycans terminated by an α2,6-linked SA that bind human strains. The mouse is often used as a model for study of influenza viruses, including recent avian strains; however, the selectivity for infection of specific respiratory cell populations is not well described, and any relationship between receptors in the mouse and human lungs is incompletely understood. Here, using in vitro human and mouse airway epithelial cell models and in vivo mouse infection, we found that the α2,3-linked SA receptor was expressed in ciliated airway and type II alveolar epithelial cells and was targeted for cell-specific infection in both species. The α2,6-linked SA receptor was not expressed in the mouse, a factor that may contribute to the inability of some human strains to efficiently infect the mouse lung. In human airway epithelial cells, α2,6-linked SA was expressed and functional in both ciliated and goblet cells, providing expanded cellular tropism. Differences in receptor and cell-specific expression in these species suggest that differentiated human airway epithelial cell cultures may be superior for evaluation of some human strains, while the mouse can provide a model for studying avian strains that preferentially bind only the α2,3-linked SA receptor.
Rinderpest Virus Blocks Type I and Type II Interferon Action: Role of Structural and Nonstructural Proteins
Authors: Nanda Sambit K. , Baron Michael D. 
Published: July 2006

ABSTRACT

Rinderpest virus
(RPV) is a paramyxovirus closely related to the human pathogen
Measles virus
. It causes severe disease in cattle, buffalo, and some wild animals; although it can infect humans, it does not cause disease. Here, we demonstrate that RPV blocks the action of both type I (α) and type II (γ) interferons (IFNs) by blocking the phosphorylation and nuclear translocation of STAT1 and STAT2 and that this block is not related to species specificity. In addition, both wild-type virulent and vaccine strains of the virus blocked IFN action. Unlike the case with some other paramyxoviruses, neither STAT1 nor STAT2 is degraded upon virus infection. STAT1 is bound by both the viral structural protein P, and thereby recruited to concentrations of viral protein in the cell, and the nonstructural protein V. Although both P and V proteins bind to STAT1 and can block IFN action when expressed in transfected cells, the IFN antagonist activity of the P protein is weaker than that of the V protein. The viral C protein also seems to weakly block IFN-induced activation of STAT1 in transfection experiments. However, studies with knockout viruses showed that the viral V protein appears to be the dominant inhibitor of IFN signaling in the context of virus infection, since prevention of viral V expression restored the IFN sensitivity of infected cells. Although a change in the distribution pattern of STAT2 was observed in virus-infected cells, STAT2 was not bound by any viral protein.
Apoptin Nucleocytoplasmic Shuttling Is Required for Cell Type-Specific Localization, Apoptosis, and Recruitment of the Anaphase-Promoting Complex/Cyclosome to PML Bodies
Authors: Heilman Destin W. , Teodoro Jose G. , Green Michael R. 
Published: July 2006

ABSTRACT

The chicken anemia virus protein Apoptin selectively induces apoptosis in transformed cells while leaving normal cells intact. This selectivity is thought to be largely due to cell type-specific localization: Apoptin is cytoplasmic in primary cells and nuclear in transformed cells. The basis of Apoptin cell type-specific localization and activity remains to be determined. Here we show that Apoptin is a nucleocytoplasmic shuttling protein whose localization is mediated by an N-terminal nuclear export signal (NES) and a C-terminal nuclear localization signal (NLS). Both signals are required for cell type-specific localization, since Apoptin fragments containing either the NES or the NLS fail to differentially localize in transformed and primary cells. Significantly, cell type-specific localization can be conferred in
trans
by coexpression of the two separate fragments, which interact through an Apoptin multimerization domain. We have previously shown that Apoptin interacts with the APC1 subunit of the anaphase-promoting complex/cyclosome (APC/C), resulting in G
2
/M cell cycle arrest and apoptosis in transformed cells. We found that the nucleocytoplasmic shuttling activity is critical for efficient APC1 association and induction of apoptosis in transformed cells. Interestingly, both Apoptin multimerization and APC1 interaction are mediated by domains that overlap with the NES and NLS sequences, respectively. Apoptin expression in transformed cells induces the formation of PML nuclear bodies and recruits APC/C to these subnuclear structures. Our results reveal a mechanism for the selective killing of transformed cells by Apoptin.
New N4-Hydroxycytidine Derivatives: Synthesis and Antiviral Activity
Authors: Ivanov Maksim A. , Antonova Elena V. , Maksimov Aleksey V. , Pigusova Lyudmila K. , Belanov Evgenii F. , Aleksandrova Lyudmila A. 
Published: July 2006

Two series of N4-hydroxycytidine derivatives were synthesized and evaluated as potential antipox virus agents. Acylation of N4-hydroxycytidine (1) with an excess of acyl chloride or imidazolide yielded the corresponding N4-(acyloxy) derivatives. 5'-Phosphonates of 1 were prepared by the reaction of cytidine 5'-phosphonates with aqueous hydroxylamine hydrochloride (pH 6.0). Nucleoside 1 and its N4-(acyloxy) derivatives inhibited replication of pox viruses in cell cultures, N4-(pivaloyloxy)- and N4-(benzoyloxy)cytidines being the most potent. The synthesized 5'-phosphonates were more cytotoxic than the parent nucleoside.
Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue microarray analysis
Authors: Mhawech-Fauceglia Paulette , Saxena Rhakee , Zhang Shaozeng , Terracciano Luigi , Sauter Guido , Chadhuri Arundhuti , Herrmann Francois R , Penetrante Remedios 
Published: July 2006

Background:Pax-5 belongs to thePaxgene family transcription factors that play an important role in organogenesis and in B cell ontogeny. It is expressed in B cell non-Hodgkin’s lymphoma (B-NHL), Hodgkin’s lymphoma (HL) and neuroendocrine carcinomas. However, its expression in other tumour types is not fully explored.Aims and methods:To determine Pax-5 expression in other tumour types, immunohistochemistry was performed on 3758 benign and malignant tumours using multiple tumour microarrays, as well as on whole sections.Results:Pax-5 was expressed in 108/118 (91.5%) B-NHLs, in 60/70 (85.7%) HLs and in 0/7 T cell lymphomas. In addition, Pax-5 was seen in 24/34 (70.6%) Merkel cell carcinomas, 42/53 (79.2%) small cell carcinomas, 1/164 (0.6%) breast carcinomas, 2/204 (1%) endometrial adenocarcinomas and 1/452 (0.2%) urothelial carcinoma of the bladder.Conclusion:Despite its expression in a small subset of malignancies of epithelial origin, Pax-5 is still a good and reliable immunomarker in diagnosing B-NHL, HL and neuroendocrine carcinomas.
VARIABILITY DESIGN TECHNIQUES FOR ENHANCING COMPONENT REUSABILITY
Authors: KIM CHUL JIN , CHO EUN SOOK , KIM SOO DONG 
Published: July 2006

Components should provide variability in satisfying a variety of domains [1], but it is not easy to develop components which can be applied to all domains. For this reason, when using time-to-market, components are slow and reusability of the components decreases. Hence, providing the variability of components becomes an important prerequisite for a successful component-based application development project. In this paper, we propose a variability design technique that can satisfy the requirements of many different kinds of domains. This technique addresses a method for designing the variability of the behavior and the workflow in a more detailed manner, and uses an object-oriented mechanism and design patterns. One of the most important goals of this technique is to provide a practical method which can be effectively applied to component-based application development.
CONGRUENCE LIFTING OF DIAGRAMS OF FINITE BOOLEAN SEMILATTICES REQUIRES LARGE CONGRUENCE VARIETIES
Authors: TŮMA JIŘÍ , WEHRUNG FRIEDRICH 
Published: July 2006

We construct a diagram [Formula: see text], indexed by a finite partially ordered set, of finite Boolean 〈∨, 0, 1〉-semilattices and 〈∨, 0, 1〉-embeddings, with top semilattice 24, such that for any variety V of algebras, if [Formula: see text] has a lifting, with respect to the congruence lattice functor, by algebras and homomorphisms in V, then there exists an algebra U in V such that the congruence lattice of U contains, as a 0,1-sublattice, the five-element modular nondistributive lattice M3. In particular, V has an algebra whose congruence lattice is neither join- nor meet-semidistributive Using earlier work of K. A. Kearnes and Á. Szendrei, we also deduce that V has no nontrivial congruence lattice identity. In particular, there is no functor Φ from finite Boolean semilattices and 〈∨, 0, 1〉-embeddings to lattices and lattice embeddings such that the composition Con Φ is equivalent to the identity (where Con denotes the congruence lattice functor), thus solving negatively a problem raised by P. Pudlák in 1985 about the existence of a functorial solution of the Congruence Lattice Problem.