bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Function Essential to Viral Entry Underlies the Hepatitis B Virus “a” Determinant
Authors: Salisse Jessica , Sureau Camille 
Published: July 2009

ABSTRACT
The hepatitis B virus (HBV) particles bear a receptor-binding site located in the pre-S1 domain of the large HBV envelope protein. Using the hepatitis delta virus (HDV) as a surrogate of HBV, a second infectivity determinant was recently identified in the envelope proteins antigenic loop (AGL), and its activity was shown to depend upon cysteine residues that are essential for the structure of the HBV immunodominant “a” determinant. Here, an alanine-scanning mutagenesis approach was used to precisely map the AGL infectivity determinant to a set of conserved residues, which are predicted to cluster together with cysteines in the AGL disulfide bridges network. Several substitutions suppressed both infectivity and the “a” determinant, whereas others were infectivity deficient with only a partial impact on antigenicity. Interestingly, G145R, a substitution often arising under immune pressure selection and detrimental to the “a” determinant, had no effect on infectivity. Altogether, these findings indicate that the AGL infectivity determinant is closely related to, yet separable from, the “a” determinant. Finally, a selection of HDV entry-deficient mutations were introduced at the surface of HBV virions and shown to also abrogate infection in the HBV model. Therefore, a function can at last be assigned to the orphan “a” determinant, the first-discovered marker of HBV infection. The characterization of the AGL functions at viral entry may lead to novel approaches in the development of antivirals against HBV.
Subcellular Localization of the
Barley Stripe Mosaic Virus
Triple Gene Block Proteins
Authors: Lim Hyoun-Sub , Bragg Jennifer N. , Ganesan Uma , Ruzin Steven , Schichnes Denise , Lee Mi Yeon , Vaira Anna Maria , Ryu Ki Hyun , Hammond John , Jackson Andrew O. 
Published: July 2009

ABSTRACT

Barley stripe mosaic virus
(BSMV) spreads from cell to cell through the coordinated actions of three triple gene block (TGB) proteins (TGB1, TGB2, and TGB3) arranged in overlapping open reading frames (ORFs). Our previous studies (D. M. Lawrence and A. O. Jackson, J. Virol. 75:8712-8723, 2001; D. M. Lawrence and A. O. Jackson, Mol. Plant Pathol. 2:65-75, 2001) have shown that each of these proteins is required for cell-to-cell movement in monocot and dicot hosts. We recently found (H.-S. Lim, J. N. Bragg, U. Ganesan, D. M. Lawrence, J. Yu, M. Isogai, J. Hammond, and A. O. Jackson, J. Virol. 82:4991-5006, 2008) that TGB1 engages in homologous interactions leading to the formation of a ribonucleoprotein complex containing viral genomic and messenger RNAs, and we have also demonstrated that TGB3 functions in heterologous interactions with TGB1 and TGB2. We have now used
Agrobacterium tumefaciens
-mediated protein expression in
Nicotiana benthamiana
leaf cells and site-specific mutagenesis to determine how TGB protein interactions influence their subcellular localization and virus spread. Confocal microscopy revealed that the TGB3 protein localizes at the cell wall (CW) in close association with plasmodesmata and that the deletion or mutagenesis of a single amino acid at the immediate C terminus can affect CW targeting. TGB3 also directed the localization of TGB2 from the endoplasmic reticulum to the CW, and this targeting was shown to be dependent on interactions between the TGB2 and TGB3 proteins. The optimal localization of the TGB1 protein at the CW also required TGB2 and TGB3 interactions, but in this context, site-specific TGB1 helicase motif mutants varied in their localization patterns. The results suggest that the ability of TGB1 to engage in homologous binding interactions is not essential for targeting to the CW. However, the relative expression levels of TGB2 and TGB3 influenced the cytosolic and CW distributions of TGB1 and TGB2. Moreover, in both cases, localization at the CW was optimal at the 10:1 TGB2-to-TGB3 ratios occurring in virus infections, and mutations reducing CW localization had corresponding effects on BSMV movement phenotypes. These data support a model whereby TGB protein interactions function in the subcellular targeting of movement protein complexes and the ability of BSMV to move from cell to cell.
Maintenance of an Old World Betasatellite by a New World Helper Begomovirus and Possible Rapid Adaptation of the Betasatellite
Authors: Nawaz-ul-Rehman Muhammad Shah , Mansoor Shahid , Briddon Rob W. , Fauquet Claude M. 
Published: July 2009

ABSTRACT

Begomoviruses (family
Geminiviridae
) cause major losses to crops throughout the tropical regions of the world. Begomoviruses originating from the New World (NW) and the Old World (OW) are genetically distinct. Whereas the majority of OW begomoviruses have monopartite genomes and whereas most of these associate with a class of symptom-modulating satellites (known as betasatellites), the genomes of NW begomoviruses are exclusively bipartite and do not associate with satellites. Here, we show for the first time that a betasatellite (cotton leaf curl Multan betasatellite [CLCuMuB]) associated with a serious disease of cotton across southern Asia is capable of interacting with a NW begomovirus. In the presence of CLCuMuB, the symptoms of the NW cabbage leaf curl virus (CbLCuV) are enhanced in
Nicotiana benthamiana
. However, CbLCuV was unable to interact with a second betasatellite, chili leaf curl betasatellite. Although CbLCuV can transreplicate CLCuMuB, satellite accumulation levels in plants were low. However, progeny CLCuMuB isolated after just one round of infection with CbLCuV contained numerous mutations. Reinoculation of one such progeny CLCuMuB with CbLCuV to
N. benthamiana
yielded infections with significantly higher satellite DNA levels. This suggests that betasatellites can rapidly adapt for efficient transreplication by a new helper begomovirus, including begomoviruses originating from the NW. Although the precise mechanism of transreplication of betasatellites by begomoviruses remains unknown, an analysis of betasatellite mutants suggests that the sequence(s) required for maintenance of CLCuMuB by one of its cognate begomoviruses (cotton leaf curl Rajasthan virus) differs from the sequences required for maintenance by CbLCuV. The significance of these findings and, particularly, the threat that betasatellites pose to agriculture in the NW, are discussed.
Random Insertion Mutagenesis of Sindbis Virus Nonstructural Protein 2 and Selection of Variants Incapable of Downregulating Cellular Transcription
Authors: Frolov Ilya , Garmashova Natalia , Atasheva Svetlana , Frolova Elena I. 
Published: July 2009

ABSTRACT
Sindbis virus nonstructural protein 2 (SINV nsP2) is an important determinant of virus pathogenesis and downregulation of virus-induced cell response. This protein efficiently inhibits transcription of cellular messenger and ribosomal RNAs and, thus, is capable of inhibiting the activation of genes whose products are involved in development of the antiviral response. Alphavirus nsP2 has a number of predicted functional domains, some of which were confirmed by crystal structure. Our current study demonstrated that none of the putative or known structural domains alone or their combinations was capable of functioning in transcription inhibition. By using random, transposon-mediated mutagenesis, we generated a library of SINV nsP2 variants having short peptide insertions and selected those that lost the ability to inhibit cellular transcription and cause a cytopathic effect. Insertions abrogating the nuclear functions of the protein were found in the three different functional nsP2 domains. Some of the mutated protein variants retained the enzymatic functions required for replication of the viral genome. Such viruses were capable of efficient, productive replication in cells defective in interferon (IFN) signaling but were attenuated and incapable of spreading in cells with an intact type I IFN response. These results revealed new information about the structure of SINV nsP2 and interaction of its domains.
Assembly and Disassembly of the Capsid-Like External Scaffold of Immature Virions during Vaccinia Virus Morphogenesis
Authors: Bisht Himani , Weisberg Andrea S. , Szajner Patricia , Moss Bernard 
Published: July 2009

ABSTRACT
Infectious poxvirus particles are unusual in that they are brick shaped and lack symmetry. Nevertheless, an external honeycomb lattice comprised of a capsid-like protein dictates the spherical shape and size of immature poxvirus particles. In the case of vaccinia virus, trimers of 63-kDa D13 polypeptides form the building blocks of the lattice. In the present study, we addressed two questions: how D13, which has no transmembrane domain, associates with the immature virion (IV) membrane to form the lattice structure and how this scaffold is removed during the subsequent stage of morphogenesis. Interaction of D13 with the A17 membrane protein was demonstrated by immunoaffinity purification and Western blot analysis. In addition, the results of immunogold electron microscopy indicated a close association of A17 and D13 in crescents, as well as in vesicular structures when crescent formation was prevented. Further studies indicated that binding of A17 to D13 was abrogated by truncation of the N-terminal segment of A17. The N-terminal region of A17 was also required for the formation of crescent and IV structures. Disassembly of the D13 scaffold correlated with the processing of A17 by the I7 protease. When I7 expression was repressed, D13 was retained on aberrant virus particles. Furthermore, the morphogenesis of IVs to mature virions was blocked by mutation of the N-terminal but not the C-terminal cleavage site on A17. Taken together, these data indicate that A17 and D13 interactions regulate the assembly and disassembly of the IV scaffold.
Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier
Authors: Gralinski Lisa E. , Ashley Shanna L. , Dixon Shandee D. , Spindler Katherine R. 
Published: July 2009

ABSTRACTInfection with mouse adenovirus type 1 (MAV-1) results in fatal acute encephalomyelitis in susceptible mouse strains via infection of brain endothelial cells. Wild-type (wt) MAV-1 causes less brain inflammation than an early region 3 (E3) null virus in C57BL/6 mice. A mouse brain microvascular endothelial cell line infected with wt MAV-1 had higher expression of mRNAs for the proinflammatory chemokines CCL2 and CCL5 than mock- and E3 null virus-infected cells. Primary mouse brain endothelial cells infected with wt virus had elevated levels of CCL2 compared to mock- or E3 null virus-infected cells. Infection of C57BL/6 mice with wt MAV-1 or the E3 null virus caused a dose-dependent breakdown of the blood-brain barrier, primarily due to direct effects of virus infection rather than inflammation. The tight junction proteins claudin-5 and occludin showed reduced surface expression on primary mouse brain endothelial cells following infection with either wt MAV-1 or the E3 null virus. mRNAs and protein for claudin-5, occludin, and zona occludens 2 were also reduced in infected cells. MAV-1 infection caused a loss of transendothelial electrical resistance in primary mouse brain endothelial cells that was not dependent on E3 or on MAV-1-induced CCL2 expression. Taken together, these results demonstrate that MAV-1 infection caused breakdown of the blood-brain barrier accompanied by decreased surface expression of tight junction proteins. Furthermore, while the MAV-1-induced pathogenesis and inflammation were dependent on E3, MAV-1-induced breakdown of the blood-brain barrier and alteration of endothelial cell function were not dependent on E3 or CCL2.
Recruitment of the Transcriptional Coactivator HCF-1 to Viral Immediate-Early Promoters during Initiation of Reactivation from Latency of Herpes Simplex Virus Type 1
Authors: Whitlow Zackary W. , Kristie Thomas M. 
Published: July 2009

ABSTRACT
The transcriptional coactivator host cell factor 1 (HCF-1) is critical for the expression of immediate-early (IE) genes of the alphaherpesviruses herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. HCF-1 may also be involved in the reactivation of these viruses from latency as it is sequestered in the cytoplasm of sensory neurons but is rapidly relocalized to the nucleus upon stimulation that results in reactivation. Here, chromatin immunoprecipitation assays demonstrate that HCF-1 is recruited to IE promoters of viral genomes during the initiation of reactivation, correlating with RNA polymerase II occupancy and IE expression. The data support the model whereby HCF-1 plays a pivotal role in the reactivation of HSV-1 from latency.
Distinctive Effects of the Epstein-Barr Virus Family of Repeats on Viral Latent Gene Promoter Activity and B-Lymphocyte Transformation
Authors: Ali Ahmed K. M. , Saito Satoru , Shibata Sachiko , Takada Kenzo , Kanda Teru 
Published: July 2009

ABSTRACT

The Epstein-Barr virus (EBV), a human B-lymphotropic gamma herpesvirus, contains multiple repetitive sequences within its genome. A group of repetitive sequences, known as the family of repeats (FR), contains multiple binding sites for the viral
trans
-acting protein EBNA-1. The FR sequences are important for viral genome maintenance and for the regulation of the promoter involved in viral latent gene expression. It has been reported that a palindromic sequence with a putative secondary structure exists at the 3′ end of the FR in the genome of the EBV B95-8 strain and that this palindromic sequence has been deleted from the FR of the commonly used EBV miniplasmids. For the first time, we cloned an EBV B95-8 DNA fragment containing the full-length FR, which enabled us to examine the functional difference between full-length and deleted FRs. The full-length FR, like the deleted FR, functioned as a transcriptional enhancer of the viral latent gene promoter, but that transactivation was significantly attenuated in the case of the full-length FR. No significant enhancement of replication was observed when the deleted FR was replaced with the full-length FR in an EBV miniplasmid. By contrast, when the same set of FR sequences were tested in the context of the complete EBV genome, the full-length FR resulted in more-efficient B-cell transformation than the deleted FR. We propose that the presence of the full-length FR contributes to the precise regulation of the viral latent promoter and increases the efficiency of B-cell transformation.
Viral Persistence and Chronic Immunopathology in the Adult Central Nervous System following Coxsackievirus Infection during the Neonatal Period
Authors: Feuer Ralph , Ruller Chelsea M. , An Naili , Tabor-Godwin Jenna M. , Rhoades Ross E. , Maciejewski Sonia , Pagarigan Robb R. , Cornell Christopher T. , Crocker Stephen J. , Kiosses William B. , Pham-Mitchell Ngan , Campbell Iain L. , Whitton J. Lindsay 
Published: July 2009

ABSTRACTCoxsackieviruses are significant human pathogens, and the neonatal central nervous system (CNS) is a major target for infection. Despite the extreme susceptibility of newborn infants to coxsackievirus infection and viral tropism for the CNS, few studies have been aimed at determining the long-term consequences of infection on the developing CNS. We previously described a neonatal mouse model of coxsackievirus B3 (CVB3) infection and determined that proliferating stem cells in the CNS were preferentially targeted. Here, we describe later stages of infection, the ensuing inflammatory response, and subsequent lesions which remain in the adult CNS of surviving animals. High levels of type I interferons and chemokines (in particular MCP-5, IP10, and RANTES) were upregulated following infection and remained at high levels up to day 10 postinfection (p.i). Chronic inflammation and lesions were observed in the hippocampus and cortex of surviving mice for up to 9 months p.i. CVB3 RNA was detected in the CNS up to 3 months p.i at high abundance (∼106genomes/mouse brain), and viral genomic material remained detectable in culture after two rounds of in vitro passage. These data suggest that CVB3 may persist in the CNS as a low-level, noncytolytic infection, causing ongoing inflammatory lesions. Thus, the effects of a relatively common infection during the neonatal period may be long lasting, and the prognosis for newborn infants recovering from acute infection should be reexplored.
Is cancer risk of radiation workers larger than expected?
Authors: Jacob P , Rühm W , Walsh L , Blettner M , Hammer G , Zeeb H 
Published: July 2009

Occupational exposures to ionising radiation mainly occur at low-dose rates and may accumulate effective doses of up to several hundred milligray.The objective of the present study is to evaluate the evidence of cancer risks from such low-dose-rate, moderate-dose (LDRMD) exposures.Our literature search for primary epidemiological studies on cancer incidence and mortality risks from LDRMD exposures included publications from 2002 to 2007, and an update of the UK National Registry for Radiation Workers study. For each (LDRMD) study we calculated the risk for the same types of cancer among the atomic bomb survivors with the same gender proportion and matched quantities for dose, mean age attained and mean age at exposure. A combined estimator of the ratio of the excess relative risk per dose from the LDRMD study to the corresponding value for the atomic bomb survivors was 1.21 (90% CI 0.51 to 1.90).The present analysis does not confirm that the cancer risk per dose for LDRMD exposures is lower than for the atomic bomb survivors. This result challenges the cancer risk values currently assumed for occupational exposures.
INDIVIDUAL AND SOCIAL STRATEGIES TO DEAL WITH IGNORANCE SITUATIONS IN MULTI-PERSON DECISION MAKING
Authors: ALONSO S. , HERRERA-VIEDMA E. , CHICLANA F. , HERRERA F. 
Published: July 2009

Multi-person decision making problems involve the preferences of some experts about a set of alternatives in order to find the best one. However, sometimes experts might not possess a precise or sufficient level of knowledge of part of the problem and as a consequence that expert might not give all the information that is required. Indeed, this may be the case when the number of alternatives is high and experts are using fuzzy preference relations to represent their preferences. In the literature, incomplete information situations have been studied, and as a result, procedures that are able to compute the missing information of a preference relation have been designed. However, these approaches usually need at least a piece of information about every alternative in the problem in order to be successful in estimating all the missing preference values. In this paper, we address situations in which an expert does not provide any information about a particular alternative, which we call situations of total ignorance. We analyze several strategies to deal with these situations. We classify these strategies into: (i) individual strategies that can be applied to each individual preference relation without taking into account any information from the rest of experts and (ii) social strategies, that is, strategies that make use of the information available from the group of experts. Both individual and social strategies use extra assumptions or knowledge, which could not be directly instantiated in the experts preference relations. We also provide an analysis of the advantages and disadvantages of each one of the strategies presented, and the situations where some of them may be more adequate to be applied than the others.
Strong Convergence of a New Iteration for a Finite Family of Accretive Operators
Authors: Hu Liang-Gen , Wang Jin-Ping 
Published: July 2009

AbstractThe viscosity approximation methods are employed to establish strong convergence of the modified Mann iteration scheme to a common zero of a finite family of accretive operators on a strictly convex Banach space with uniformly Gâteaux differentiable norm. Our work improves and extends various results existing in the current literature.
Bi-modal Structure and Variability of Large-Scale Diabatic Heating in the Tropics
Authors: Zhang Chidong , Hagos Samson M. 
Published: July 2009

Abstract
Tropical diabatic heating profiles estimated using sounding data from eight field campaigns were diagnosed to document their common and prevailing structure and variability that are relevant to the large-scale circulation. The first two modes of a rotated empirical orthogonal function analysis—one deep, one shallow—explain 85% of the total variance of all data combined. These two modes were used to describe the heating evolution, which led to three composited heating profiles that are considered as prevailing large-scale heating structures. They are, respectively, shallow, bottom heavy (peak near 700 hPa); deep, middle heavy (peak near 400 hPa); and stratiform-like, top heavy (heating peak near 400 hPa and cooling peak near 700 hPa). The amplitudes and occurrence frequencies of the shallow, bottom-heavy heating profiles are comparable to those of the stratiform-like, top-heavy ones. The sequence of the most probable heating evolution is deep tropospheric cooling to bottom-heavy heating, to middle heavy heating, to stratiform-like heating, then back to deep tropospheric cooling. This heating transition appears to occur on different time scales. Each of the prevailing heating structures is interpreted as being composed of particular fractional populations of various types of precipitating cloud systems, which are viewed as the building blocks for the mean. A linear balanced model forced by the three prevailing heating profiles produces rich vertical structures in the circulation with multiple overturning cells, whose corresponding moisture convergence and surface wind fields are very sensitive to the heating structures.
Influence of ENSO and the Atlantic Multidecadal Oscillation on Drought over the United States
Authors: Mo Kingtse C. , Schemm Jae-Kyung E. , Yoo Soo-Hyun 
Published: July 2009

Abstract
Composites based on observations and model outputs from the Climate Variability and Predictability (CLIVAR) drought experiments were used to examine the impact of El Niño–Southern Oscillation (ENSO) and the Atlantic multidecadal oscillation (AMO) on drought over the United States. Because drought implies persistent dryness, the 6-month standardized precipitation index, standardized runoff index, and soil moisture anomalies are used to represent drought. The experiments were performed by forcing an AGCM with prescribed sea surface temperature anomalies (SSTAs) superimposed on the monthly mean SST climatology. Four model outputs from the NCEP Global Forecast System (GFS), NASA’s Seasonal-to-Interannual Prediction Project, version 1 (NSIPP1), GFDL’s global atmospheric model, version 2.1 (AM2.1), and the Lamont-Doherty Earth Observatory (LDEO)/NCAR Community Climate System Model, version 3 (CCM3) were analyzed in this study. Each run lasts from 36 to 51 yr.
The impact of ENSO on drought over the United States is concentrated over the Southwest, the Great Plains, and the lower Colorado River basin, with cold (warm) ENSO events favoring drought (wet spells). Over the East Coast and the Southeast, the impact of ENSO is small because the precipitation responses to ENSO are opposite in sign for winter and summer. For these areas, a prolonged ENSO does not always favor either drought or wet spells.
The direct influence of the AMO on drought is small. The major influence of the AMO is to modulate the impact of ENSO on drought. The influence is large when the SSTAs in the tropical Pacific and in the North Atlantic are opposite in phase. A cold (warm) event in a positive (negative) AMO phase amplifies the impact of the cold (warm) ENSO on drought. The ENSO influence on drought is much weaker when the SSTAs in the tropical Pacific and in the North Atlantic are in phase.