bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structure of an Aquabirnavirus Particle: Insights into Antigenic Diversity and Virulence Determinism
Authors: Coulibaly Fasséli , Chevalier Christophe , Delmas Bernard , Rey Félix A. 
Published: December 2009

ABSTRACT

Infectious pancreatic necrosis virus (IPNV), a pathogen of salmon and trout, imposes a severe toll on the aquaculture and sea farming industries. IPNV belongs to the
Aquabirnavirus
genus in the
Birnaviridae
family of bisegmented double-stranded RNA viruses. The virions are nonenveloped with a T=13
l
icosahedral capsid made by the coat protein VP2, the three-dimensional (3D) organization of which is known in detail for the family prototype, the infectious bursal disease virus (IBDV) of poultry. A salient feature of the birnavirus architecture is the presence of 260 trimeric spikes formed by VP2, projecting radially from the capsid. The spikes carry the principal antigenic sites as well as virulence and cell adaptation determinants. We report here the 3.4-Å resolution crystal structure of a subviral particle (SVP) of IPNV, containing 20 VP2 trimers organized with icosahedral symmetry. We show that, as expected, the SVPs have a very similar organization to the IBDV counterparts, with VP2 exhibiting the same overall 3D fold. However, the spikes are significantly different, displaying a more compact organization with tighter packing about the molecular 3-fold axis. Amino acids controlling virulence and cell culture adaptation cluster differently at the top of the spike, i.e., in a central bowl in IBDV and at the periphery in IPNV. In contrast, the spike base features an exposed groove, conserved across birnavirus genera, which contains an integrin-binding motif. Thus, in addition to revealing the viral antigenic determinants, the structure suggests that birnaviruses interact with different receptors for attachment and for cell internalization during entry.
An N-Terminal Region of Lassa Virus L Protein Plays a Critical Role in Transcription but Not Replication of the Virus Genome
Authors: Lelke Michaela , Brunotte Linda , Busch Carola , Günther Stephan 
Published: December 2009

ABSTRACT
The central domain of the 200-kDa Lassa virus L protein is a putative RNA-dependent RNA polymerase. N- and C-terminal domains may harbor enzymatic functions important for viral mRNA synthesis, including capping enzymes or cap-snatching endoribonucleases. In the present study, we have employed a large-scale mutagenesis approach to map functionally relevant residues in these regions. The main targets were acidic (Asp and Glu) and basic residues (Lys and Arg) known to form catalytic and binding sites of capping enzymes and endoribonucleases. A total of 149 different mutants were generated and tested in the Lassa virus replicon system. Nearly 25% of evolutionarily highly conserved acidic and basic side chains were dispensable for function of L protein in the replicon context. The vast majority of the remaining mutants had defects in both transcription and replication. Seven residues (Asp-89, Glu-102, Asp-119, Lys-122, Asp-129, Glu-180, and Arg-185) were selectively important for mRNA synthesis. The phenotype was particularly pronounced for Asp-89, Glu-102, and Asp-129, which were indispensable for transcription but could be replaced by a variety of amino acid residues without affecting genome replication. Bioinformatics disclosed the remote similarity of this region to type IIs endonucleases. The mutagenesis was complemented by experiments with the RNA polymerase II inhibitor α-amanitin, demonstrating dependence of viral transcription from the cellular mRNA pool. In conclusion, this paper describes an N-terminal region in L protein being important for mRNA, but not genome synthesis. Bioinformatics and cell biological experiments lend support to the hypothesis that this region could be part of a cap-snatching enzyme.
The NS Segment of an H5N1 Highly Pathogenic Avian Influenza Virus (HPAIV) Is Sufficient To Alter Replication Efficiency, Cell Tropism, and Host Range of an H7N1 HPAIV
Authors: Ma Wenjun , Brenner Dominique , Wang Zhongfang , Dauber Bianca , Ehrhardt Christina , Högner Katrin , Herold Susanne , Ludwig Stephan , Wolff Thorsten , Yu Kangzhen , Richt Jürgen A. , Planz Oliver , Pleschka Stephan 
Published: December 2009

ABSTRACT

A reassortant avian influenza virus (designated FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (GD; H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (FPV; H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild-type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 proteins of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of cleavage and polyadenylation specificity factor 30 (CPSF30) with comparable efficiencies
in vitro
. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition, and (iii) stronger beta interferon promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of an H5N1 strain for viral replication, molecular pathogenicity, and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7 and H5 type HPAIVs.
The Murine Coronavirus Nucleocapsid Gene Is a Determinant of Virulence
Authors: Cowley Timothy J. , Long Simon Y. , Weiss Susan R. 
Published: December 2009

ABSTRACT
The murine coronavirus, mouse hepatitis virus (MHV) strain A59, causes acute encephalitis and chronic demyelinating disease as well as hepatitis in mice. The JHM strain (also called MHV-4 or JHM.SD) causes fatal encephalitis and only minimal hepatitis. Previous analysis of chimeric recombinant MHVs in which the spike gene, encoding the protein that mediates viral entry and cell-to-cell fusion, was exchanged between JHM and A59 showed that the spike plays a major role in determining organ tropism and neurovirulence but that other genes also play important roles in pathogenic outcome. Here, we have investigated the role of the nucleocapsid protein in MHV-induced disease. The multifunctional nucleocapsid protein is complexed with the genomic RNA, interacts with the viral membrane protein during virion assembly, and plays an import role in enhancing the efficiency of transcription. A pair of chimeric recombinant viruses in which the nucleocapsid gene was exchanged between JHM and A59 was selected and compared to wild-type parental strains in terms of virulence. Importantly, expression of the JHM nucleocapsid in the context of the A59 genome conferred increased mortality and spread of viral antigen in the mouse central nervous system compared to the parental A59 strain, while having little effect on the induction of hepatitis. While the JHM nucleocapsid did not appear to enhance neuron-to-neuron spread in primary neuronal cultures, the increased neurovirulence it conferred may be due in part to the induction of a less robust T-cell response than that induced by strain A59.
Importance of Hydrogen Bond Contacts between the N Protein and RNA Genome of Vesicular Stomatitis Virus in Encapsidation and RNA Synthesis
Authors: Rainsford Edward W. , Harouaka Djamila , Wertz Gail W. 
Published: December 2009

ABSTRACT
Vesicular stomatitis virus (VSV) genomic RNA encapsidated by the nucleocapsid (N) protein is the template for transcription and replication by the viral polymerase. We analyzed the 2.9-Å structure of the VSV N protein bound to RNA (T. J. Green, X. Zhang, G. W. Wertz, and M. Luo, Science 313:357-360, 2006) and identified amino acid residues with the potential to interact with RNA via hydrogen bonds. The contributions of these interactions to N protein function were investigated by individually substituting the residues with alanine and assaying the effect of these mutations on N protein expression, on the ability of the N protein to interact with the phosphoprotein (P), and on its ability to encapsidate RNA and generate templates that can support transcription and RNA replication. These studies identified individual amino acids critical for N protein function. Nine nucleotides are associated with each N monomer and contorted into two quasi-helices within the N protein RNA binding cavity. We found that N protein residues that formed hydrogen bond contacts with the nucleotides in quasi-helix 2 were critical to the encapsidation of RNA and the production of templates that can support RNA synthesis. Individual hydrogen bond interactions between the N protein and the nucleotides of quasi-helix 1 were not essential for ribonucleoprotein (RNP) template function. Residue R143 forms a hydrogen bond with nucleotide 9, the nucleotide that extends between N monomers. R143A mutant N protein failed to encapsidate RNA and to support RNA synthesis and suppressed wild-type N protein function. These studies show a direct correlation between viral RNA synthesis and N protein residues structurally positioned to interact with RNA.
Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction
Authors: Schulze Andreas , Schieck Alexa , Ni Yi , Mier Walter , Urban Stephan 
Published: December 2009

ABSTRACT

Previous studies showed that the N-terminal 75 amino acids of the pre-S1 domain of the hepatitis B virus (HBV) L protein are essential for HBV and hepatitis delta virus (HDV) infectivity. Consistently, synthetic lipopeptides encompassing this sequence or only parts of it efficiently block HBV and HDV infection, presumably through specific interference with a cellular receptor. Crucial for both virus infectivity and the inhibitory activity of the peptides are N-terminal myristoylation and a highly conserved motif within the N-terminal 48 amino acids. To refine the sequence requirements, we synthesized a series of HBV pre-S1 peptides containing deletions, point mutations,
d
-amino acid exchanges, or genotype-specific sequence permutations. Using the HepaRG cell line and a genotype D-derived virus, we determined the specific inhibitory activities of the peptides and found that (i) lipopeptides with an artificial consensus sequence inhibit HBV genotype D infection more potently than the corresponding genotype D peptides; (ii) point mutations,
d
-amino acid exchanges, or deletions introduced into the highly conserved part of the pre-S1 domain result in an almost complete loss of activity; and (iii) the flanking sequences comprising amino acids 2 to 8, 16 to 20, and, to a less pronounced extent, 34 to 48 gradually increase the inhibitory activity, while amino acids 21 to 33 behave indifferently. Taken together, our data suggest that HBV pre-S1-mediated receptor interference and, thus, HBV receptor recognition form a highly specific process. It requires an N-terminal acyl moiety and a highly conserved sequence that is present in primate but not rodent or avian hepadnaviruses, indicating different entry pathways for the different family members.
During Lytic Infections, Herpes Simplex Virus Type 1 DNA Is in Complexes with the Properties of Unstable Nucleosomes
Authors: Lacasse Jonathan J. , Schang Luis M. 
Published: December 2009

ABSTRACT
The genomes of herpes simplex virus type 1 (HSV-1) are regularly chromatinized during latency such that their digestion with micrococcal nuclease (MCN) releases nucleosome-sized DNA fragments. In lytically infected cells, in contrast, MCN releases HSV-1 DNA in primarily heterogeneously sized fragments. Consistently, only a small percentage of this HSV-1 DNA coimmunoprecipitates with histones. Most current models propose that histones associate with HSV-1 DNA during lytic infections at low occupancy. However, histone modification or occupation is also proposed to regulate HSV-1 transcription. It remains unclear how the histones associated with a small percentage of HSV-1 DNA may regulate transcription globally. Moreover, the physical properties of the complexes containing histones and HSV-1 DNA are unknown. We evaluated the HSV-1 DNA-containing complexes at 5 h after (lytic) infection by biochemical fractionations. Nuclear HSV-1 DNA did not fractionate as protein-free HSV-1 DNA but as DNA in cellular nucleosomes. Moreover, MCN released HSV-1 DNA in complexes that fractionate as cellular mono- and dinucleosomes by centrifugation followed by sucrose gradients and size-exclusion chromatography. The HSV-1 DNA in such complexes was protected to heterogeneous sizes and was more accessible to MCN than DNA in most cellular chromatin. Using a modified MCN digestion to trap unstable digestion intermediates, HSV-1 DNA was quantitatively recovered in discrete mono- to polynucleosome sizes in complexes fractionating as cellular mono- to polynucleosomes. The HSV-1 DNAs in complexes fractionating as mono- to dinucleosomes were stabilized by cross-linking. Therefore, most HSV-1 DNA forms particularly unstable nucleosome-like complexes at 5 h of lytic infection.
Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic
Authors: Xu Rui , McBride Ryan , Paulson James C. , Basler Christopher F. , Wilson Ian A. 
Published: December 2009

ABSTRACT
The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 Å resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.
Rotavirus Infection Activates Dendritic Cells from Peyer's Patches in Adult Mice
Authors: Lopez-Guerrero Delia V. , Meza-Perez Selene , Ramirez-Pliego Oscar , Santana-Calderon Maria A. , Espino-Solis Pavel , Gutierrez-Xicotencatl Lourdes , Flores-Romo Leopoldo , Esquivel-Guadarrama Fernando R. 
Published: December 2009

ABSTRACTThis study used anin vivomouse model to analyze the response of dendritic cells (DCs) in Peyer's patches (PPs) within the first 48 h of infection with the wild-type murine rotavirus EDIM (EDIMwt). After the infection, the absolute number of DCs was increased by 2-fold in the PPs without a modification of their relative percentage of the total cell number. Also, the DCs from PPs of infected mice showed a time-dependent migration to the subepithelial dome (SED) and an increase of the surface activation markers CD40, CD80, and CD86. This response was more evident at 48 h postinfection (p.i.) and depended on viral replication, since DCs from PPs of mice inoculated with UV-treated virus did not show this phenotype. As a result of the activation, the DCs showed an increase in the expression of mRNA for the proinflammatory cytokines interleukin-12/23p40 (IL-12/23p40), tumor necrosis factor alpha (TNF-α), and beta interferon (IFN-β), as well as for the regulatory cytokine IL-10. These results suggest that, a short time after rotavirus infection, the DCs from PPs play a critical role in controlling the infection and, at the same time, avoiding an excessive inflammatory immune response.
"In Jesus' Name": A Key Resource on the Worldwide Pentecostal Phenomenon & the Oneness, Apostolic, or Jesus' Name Movement
Authors: French Talmadge 
Published: December 2009

AbstractThe review summarizes the implications of David Reed's excellent study of Oneness Pentecostalism as a major treatment of the movement in which the sections regarding its background, history, and theology are equally comprehensive. Reed's work sets the movement, not in the context of its global expansion and impact, but within the context of its historical development amidst an array of Evangelical-Pentecostal tensions. It characterizes the movement as a sect, rather than a cult, and as a worldwide expression of Pentecostalism in its own right. This review, therefore, explores Reed's argumentation in which he explains its historical development as a movement rooted, first and foremost, in pietism, especially Wesleyan, which used Jewish categories, similar to the practice of early Jewish rather than Nicene Christianity. Reed contends that a tendency towards a Jesus-centric 'reductionism' in Evangelicalism shaped the movement and most of its patterns of doctrinal 'imbalances.' The specific setting for this influence is seen as the theology of William Durham, specifically, and the restoration impulses of Pentecostalism, generally.
Improved Global Rainfall Retrieval Using the Special Sensor Microwave Imager (SSM/I)
Authors: Vila Daniel , Ferraro Ralph , Semunegus Hilawe 
Published: December 2009

Abstract
Global monthly rainfall estimates have been produced from more than 20 years of measurements from the Defense Meteorological Satellite Program series of Special Sensor Microwave Imager (SSM/I). This is the longest passive microwave dataset available to analyze the seasonal, annual, and interannual rainfall variability on a global scale. The primary algorithm used in this study is an 85-GHz scattering-based algorithm over land, while a combined 85-GHz scattering and 19/37-GHz emission is used over ocean. The land portion of this algorithm is one of the components of the blended Global Precipitation Climatology Project rainfall climatology. Because previous SSM/I processing was performed in real time, only a basic quality control (QC) procedure had been employed to avoid unrealistic values in the input data. A more sophisticated, statistical-based QC procedure on the daily data grids (antenna temperature) was developed to remove unrealistic values not detected in the original database and was employed to reprocess the rainfall product using the current version of the algorithm for the period 1992–2007. Discrepancies associated with the SSM/I-derived monthly rainfall products are characterized through comparisons with various gauge-based and other satellite-derived rainfall estimates. A substantial reduction in biases was observed as a result of this QC scheme. This will yield vastly improved global rainfall datasets.
Determination of Precipitation Return Values in Complex Terrain and Their Evaluation
Authors: Früh Barbara , Feldmann Hendrik , Panitz Hans-Jürgen , Schädler Gerd , Jacob Daniela , Lorenz Philip , Keuler Klaus 
Published: December 2009

AbstractTo determine return values at various return periods for extreme daily precipitation events over complex orography, an appropriate threshold value and distribution function are required. The return values are calculated using the peak-over-threshold approach in which only a reduced sample of precipitation events exceeding a predefined threshold is analyzed. To fit the distribution function to the sample, the L-moment method is used. It is found that the deviation between the fitted return values and the plotting positions of the ranked precipitation events is smaller for the kappa distribution than for the generalized Pareto distribution.As a second focus, the ability of regional climate models to realistically simulate extreme daily precipitation events is assessed. For this purpose the return values are derived using precipitation events exceeding the 90th percentile of the precipitation time series and a fit of a kappa distribution. The results of climate simulations with two different regional climate models are analyzed for the 30-yr period 1971–2000: the so-called consortium runs performed with the climate version of the Lokal Modell (referred to as the CLM-CR) at 18-km resolution and the Regional Model (REMO)–Umweltbundesamt (UBA) simulations at 10-km resolution. It was found that generally the return values are overestimated by both models. Averaged across the region the overestimation is higher for REMO–UBA compared to CLM-CR.
Influence of SST Forcing on Stochastic Characteristics of Simulated Precipitation and Drought
Authors: Ferguson Ian M. , Dracup John A. , Duffy Philip B. , Pegion Philip , Schubert Siegfried 
Published: December 2009

Abstract
Recent studies demonstrate that ocean–atmosphere forcing by persistent sea surface temperature (SST) anomalies is a primary driver of seasonal-to-interannual hydroclimatic variability, including drought events. Other studies, however, conclude that although SST anomalies influence the timing of drought events, their duration and magnitude over continental regions is largely governed by land–atmosphere feedbacks. Here the authors evaluate the direct influence of SST anomalies on the stochastic characteristics of precipitation and drought in two ensembles of AGCM simulations forced with observed (interannually varying) monthly SST and their climatological annual cycle, respectively. Results demonstrate that ocean–atmosphere forcing contributes to the magnitude and persistence of simulated seasonal precipitation anomalies throughout the tropics but over few mid- and high-latitude regions. Significant autocorrelation of simulated seasonal anomalies over oceans is directly forced by persistent SST anomalies; over land, SST anomalies are shown to enhance autocorrelation associated with land–atmosphere feedbacks. SST anomalies are shown to have no significant influence on simulated drought frequency, duration, or magnitude over most midlatitude land regions. Results suggest that severe and sustained drought events may occur in the absence of persistent SST forcing and support recent conclusions that ocean–atmosphere forcing primarily influences the timing of drought events, while duration and magnitude are governed by other mechanisms such as land–atmosphere feedbacks. Further analysis is needed to assess the potential model dependence of results and to quantify the relative contribution of land–atmosphere feedbacks to the long-term stochastic characteristics of precipitation and drought.