bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against Lethal Vaccinia Virus Challenge by Using an Attenuated Matrix Protein Mutant Vesicular Stomatitis Virus Vaccine Vector Expressing Poxvirus Antigens
Authors: Braxton Cassandra L. , Puckett Shelby H. , Mizel Steven B. , Lyles Douglas S. 
Published: January 2010

ABSTRACT
Recombinant vesicular stomatitis viruses (VSV) are excellent candidate vectors for vaccination against human diseases. The neurovirulence of VSV in animal models requires the attenuation of the virus for use in humans. Previous efforts have focused on attenuating virus replication. Studies presented here test an alternative approach for attenuation that uses a matrix (M) protein mutant (rM51R) VSV as a vaccine vector against respiratory infection. This mutant is attenuated for viral virulence by its inability to suppress the innate immune response. The ability of rM51R VSV vectors to protect against lethal respiratory challenge was tested using a vaccinia virus intranasal challenge model. Mice immunized intranasally with rM51R vectors expressing vaccinia virus antigens B5R and L1R were protected against lethal vaccinia virus challenge. A single immunization with the vectors provided protection against vaccinia virus-induced mortality; however, a prime-boost strategy reduced the severity of the vaccinia virus-induced disease progression. Antibody titers measured after the prime and boost were low despite complete protection against lethal challenge. However, immunized animals had higher antibody titers during the challenge, suggesting that memory B-cell responses may be important for the protection. Depletion experiments demonstrated that B cells but not CD8 T cells were involved in the protection mediated by rM51R vaccine vectors that express B5R and L1R. These results demonstrate the potential of M protein mutant VSVs as candidate vaccine vectors against human diseases.
Simian Virus 40 Infection Triggers a Balanced Network That Includes Apoptotic, Survival, and Stress Pathways
Authors: Butin-Israeli Veronika , Drayman Nir , Oppenheim Ariella 
Published: January 2010

ABSTRACTThe infection process by simian virus 40 (SV40) and entry of its genome into nondividing cells are only partly understood. Infection begins by binding to GM1 receptors at the cell surface, cellular entry via caveolar invaginations, and trafficking to the endoplasmic reticulum, where the virus disassembles. To gain a deeper insight into the contribution of host functions to this process, we studied cellular signaling elicited by the infecting virus. Signaling proteins were detected by Western blotting and immunofluorescence staining. The study was assisted by a preliminary proteomic screen. The contribution of signaling proteins to the infection process was evaluated using specific inhibitors. We found that CV-1 cells respond to SV40 infection by activating poly(ADP-ribose) polymerase 1 (PARP-1)-mediated apoptotic signaling, which is arrested by the Akt-1 survival pathway and stress response. A single key regulator orchestrating the three pathways is phospholipase C-gamma (PLCγ). The counteracting apoptotic and survival pathways are robustly balanced as the infected cells neither undergo apoptosis nor proliferate. Surprisingly, we have found that the apoptotic pathway, including activation of PARP-1 and caspases, is absolutely required for the infection to proceed. Thus, SV40 hijacks the host defense to promote its infection. Activities of PLCγ and Akt-1 are also required, and their inhibition abrogates the infection. Notably, this signaling network is activated hours before T antigen is expressed. Experiments with recombinant empty capsids, devoid of DNA, indicated that the major capsid protein VP1 alone triggers this early signaling network. The emerging robust signaling network reflects a delicate evolutionary balance between attack and defense in the host-virus relationship.
Bicaudal D1-Dependent Trafficking of Human Cytomegalovirus Tegument Protein pp150 in Virus-Infected Cells
Authors: Indran Sabarish V. , Ballestas Mary E. , Britt William J. 
Published: January 2010

ABSTRACT
Human cytomegalovirus (HCMV) virion assembly takes place in the nucleus and cytoplasm of infected cells. The HCMV virion tegument protein pp150 (ppUL32) is an essential protein of HCMV and has been suggested to play a role in the cytoplasmic phase of HCMV assembly. To further define its role in viral assembly and to identify host cell proteins that interact with pp150 during viral assembly, we utilized yeast two-hybrid analyses to detect an interaction between pp150 and Bicaudal D1 (BicD1), a protein thought to play a role in trafficking within the secretory pathway. BicD1 is known to interact with the dynein motor complex and the Rab6 GTPase. The interaction between pp150 and BicD1 was confirmed by coimmunoprecipitation and fluorescence resonance energy transfer. Depletion of BicD1 with short hairpin RNA (shRNA) caused decreased virus yield and a defect in trafficking of pp150 to the cytoplasmic viral assembly compartment (AC), without altering trafficking to the AC of another essential tegument protein, pp28, or the viral glycoprotein complex gM/gN. The C terminus of BicD1 has been previously shown to interact with the GTPase Rab6, suggesting a potential role for Rab6-mediated vesicular trafficking in HCMV assembly. Finally, overexpression of the N terminus of truncated BicD1 acts in a dominant-negative manner and leads to disruption of the AC and a decrease in the assembly of infectious virus. This phenotype was similar to that observed following overexpression of dynamitin (p50) and provided additional evidence that morphogenesis of the AC and virus assembly were dynein dependent.
Experimental Verification of a Traceback Phenomenon in Prion Infection
Authors: Kobayashi Atsushi , Sakuma Nobuyuki , Matsuura Yuichi , Mohri Shirou , Aguzzi Adriano , Kitamoto Tetsuyuki 
Published: January 2010

ABSTRACTThe clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD) correlate with the allelotypes (M or V) of the polymorphic codon 129 of the human prion protein (PrP) gene and the electrophoretic mobility patterns of abnormal prion protein (PrPSc). Transmission of sCJD prions to mice expressing human PrP with a heterologous genotype (referred to as cross-sequence transmission) results in prolonged incubation periods. We previously reported that cross-sequence transmission can generate a new prion strain with unique transmissibility, designated a traceback phenomenon. To verify experimentally the traceback of sCJD-VV2 prions, we inoculated sCJD-VV2 prions into mice expressing human PrP with the 129M/M genotype. These 129M/M mice showed altered neuropathology and a novel PrPSctype after a long incubation period. We then passaged the brain homogenate from the 129M/M mouse inoculated with sCJD-VV2 prions into other 129M/M or 129V/V mice. Despite cross-sequence transmission, 129V/V mice were highly susceptible to these prions compared to the 129M/M mice. The neuropathology and PrPSctype of the 129V/V mice inoculated with the 129M/M mouse-passaged sCJD-VV2 prions were identical to those of the 129V/V mice inoculated with sCJD-VV2 prions. Moreover, we generated for the first time a type 2 PrPSc-specific antibody in addition to type 1 PrPSc-specific antibody and discovered that drastic changes in the PrPScsubpopulation underlie the traceback phenomenon. Here, we report the first direct evidence of the traceback in prion infection.
Novel Function of CD81 in Controlling Hepatitis C Virus Replication
Authors: Zhang Yong-Yuan , Zhang Bai-Hua , Ishii Koji , Liang T. Jake 
Published: January 2010

ABSTRACTThe mechanisms of hepatitis C virus (HCV) replication remain poorly understood, and the cellular factors required for HCV replication are yet to be completely defined. CD81 is known to mediate HCV entry. Our study uncovered an unexpected novel function of CD81 in the HCV life cycle that is important for HCV RNA replication. HCV replication occurred efficiently in infected cells with high levels of CD81 expression. In HCV-infected or RNA-transfected cells with low levels of CD81 expression, initial viral protein synthesis occurred normally, but efficient replication failed to proceed. The aborted replication could be restored by the transient transfection of a CD81 expression plasmid. CD81-dependent replication was demonstrated with both an HCV infectious cell culture and HCV replicon cells of genotypes 1b and 2a. We also showed that CD81 expression is positively correlated with the kinetics of HCV RNA synthesis but inversely related to the kinetics of viral protein production, suggesting that CD81 may control viral replication by directing viral RNA template function to RNA replication. Thus, CD81 may be necessary for the efficient replication of the HCV genome in addition to its role in viral entry.
Structure of the Dimerization Domain of the Rabies Virus Phosphoprotein
Authors: Ivanov Ivan , Crépin Thibaut , Jamin Marc , Ruigrok Rob W. H. 
Published: January 2010

ABSTRACT
The crystal structure of the dimerization domain of rabies virus phosphoprotein was determined. The monomer consists of two α-helices that make a helical hairpin held together mainly by hydrophobic interactions. The monomer has a hydrophilic and a hydrophobic face, and in the dimer two monomers pack together through their hydrophobic surfaces. This structure is very different from the dimerization domain of the vesicular stomatitis virus phosphoprotein and also from the tetramerization domain of the Sendai virus phosphoprotein, suggesting that oligomerization is conserved but not structure.
A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer
Authors: Xiang Shi-Hua , Finzi Andrés , Pacheco Beatriz , Alexander Kevin , Yuan Wen , Rizzuto Carlo , Huang Chih-Chin , Kwong Peter D. , Sodroski Joseph 
Published: January 2010

ABSTRACTHuman immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 β2, β19, β20, and β21 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding.
PI3K p110δ regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
Authors: Soond Dalya R. , Bjørgo Elisa , Moltu Kristine , Dale Verity Q. , Patton Daniel T. , Torgersen Knut Martin , Galleway Fiona , Twomey Breda , Clark Jonathan , Gaston J. S. Hill , Taskén Kjetil , Bunyard Peter , Okkenhaug Klaus 
Published: January 2010

AbstractWe have previously described critical and nonredundant roles for the phosphoinositide 3-kinase p110δ during the activation and differentiation of naive T cells, and p110δ inhibitors are currently being developed for clinical use. However, to effectively treat established inflammatory or autoimmune diseases, it is important to be able to inhibit previously activated or memory T cells. In this study, using the isoform-selective inhibitor IC87114, we show that sustained p110δ activity is required for interferon-γ production. Moreover, acute inhibition of p110δ inhibits cytokine production and reduces hypersensitivity responses in mice. Whether p110δ played a similar role in human T cells was unknown. Here we show that IC87114 potently blocked T-cell receptor–induced phosphoinositide 3-kinase signaling by both naive and effector/memory human T cells. Importantly, IC87114 reduced cytokine production by memory T cells from healthy and allergic donors and from inflammatory arthritis patients. These studies establish that previously activated memory T cells are at least as sensitive to p110δ inhibition as naive T cells and show that mouse models accurately predict p110δ function in human T cells. There is therefore a strong rationale for p110δ inhibitors to be considered for therapeutic use in T-cell–mediated autoimmune and inflammatory diseases.
The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure
Authors: Spellman Stephen , Bray Robert , Rosen-Bronson Sandra , Haagenson Michael , Klein John , Flesch Susan , Vierra-Green Cynthia , Anasetti Claudio 
Published: January 2010

Abstract
Donor-directed human leukocyte antigen (HLA)–specific allo-antibodies (DSAs) cause graft failure in animal models of hematopoietic stem cell transplantation (HCT). Archived pretransplantation sera from graft failure patients (n = 37) and a matched case-control cohort (n = 78) were tested to evaluate the role of DSAs in unrelated donor HCT. Controls were matched for disease, disease status, graft type, patient age, and transplantation year. Patients had acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; 98% received myeloablative conditioning regimens 100% received T-replete grafts, 97% received marrow, 95% HLA-mismatched, and 97% received calcineurin-based graft-versus-host disease prophylaxis. Among the 37 failed transplantations, 9 (24%) recipients possessed DSAs against HLA-A, B, and/or DP, compared with only 1 (1%) of 78 controls. Therefore, the presence of DSAs was significantly associated with graft failure (odds ratio = 22.84; 95% confidence interval, 3.57-∞; P < .001). These results indicate that the presence of pretransplantation DSAs in recipients of unrelated donor HCT is associated with failed engraftment and should be considered in HCT donor selection.
SeqTrim: a high-throughput pipeline for pre-processing any type of sequence read
Authors: Falgueras Juan , Lara Antonio J , Fernández-Pozo Noé , Cantón Francisco R , Pérez-Trabado Guillermo , Claros M Gonzalo 
Published: January 2010

Abstract

Background
High-throughput automated sequencing has enabled an exponential growth rate of sequencing data. This requires increasing sequence quality and reliability in order to avoid database contamination with artefactual sequences. The arrival of pyrosequencing enhances this problem and necessitates customisable pre-processing algorithms.

Results
SeqTrim has been implemented both as a Web and as a standalone command line application. Already-published and newly-designed algorithms have been included to identify sequence inserts, to remove low quality, vector, adaptor, low complexity and contaminant sequences, and to detect chimeric reads. The availability of several input and output formats allows its inclusion in sequence processing workflows. Due to its specific algorithms, SeqTrim outperforms other pre-processors implemented as Web services or standalone applications. It performs equally well with sequences from EST libraries, SSH libraries, genomic DNA libraries and pyrosequencing reads and does not lead to over-trimming.

Conclusions
SeqTrim is an efficient pipeline designed for pre-processing of any type of sequence read, including next-generation sequencing. It is easily configurable and provides a friendly interface that allows users to know what happened with sequences at every pre-processing stage, and to verify pre-processing of an individual sequence if desired. The recommended pipeline reveals more information about each sequence than previously described pre-processors and can discard more sequencing or experimental artefacts.
The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history
Authors: Peng Yi , Shi Hong , Qi Xue-bin , Xiao Chun-jie , Zhong Hua , Ma Run-lin Z , Su Bing 
Published: January 2010

Abstract

Background
The emergence of agriculture about 10,000 years ago marks a dramatic change in human evolutionary history. The diet shift in agriculture societies might have a great impact on the genetic makeup of Neolithic human populations. The regionally restricted enrichment of the class I alcohol dehydrogenase sequence polymorphism (ADH1BArg47His) in southern China and the adjacent areas suggests Darwinian positive selection on this genetic locus during Neolithic time though the driving force is yet to be disclosed.

Results
We studied a total of 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. The geographic distribution of the ADH1B*47His allele in these populations indicates a clear east-to-west cline, and it is dominant in south-eastern populations but rare in Tibetan populations. The molecular dating suggests that the emergence of the ADH1B*47His allele occurred about 10,000~7,000 years ago.

Conclusion
We present genetic evidence of selection on the ADH1BArg47His polymorphism caused by the emergence and expansion of rice domestication in East Asia. The geographic distribution of the ADH1B*47His allele in East Asia is consistent with the unearthed culture relic sites of rice domestication in China. The estimated origin time of ADH1B*47His allele in those populations coincides with the time of origin and expansion of Neolithic agriculture in southern China.
DIGAP - a Database of Improved Gene Annotation for Phytopathogens
Authors: Gao Na , Chen Ling-Ling , Ji Hong-Fang , Wang Wei , Chang Ji-Wei , Gao Bei , Zhang Lin , Zhang Shi-Cui , Zhang Hong-Yu 
Published: January 2010

Abstract

Background
Bacterial plant pathogens are very harmful to their host plants, which can cause devastating agricultural losses in the world. With the development of microbial genome sequencing, many strains of phytopathogens have been sequenced. However, some misannotations exist in these phytopathogen genomes. Our objective is to improve these annotations and store them in a central database DIGAP.

Description
DIGAP includes the following improved information on phytopathogen genomes. (i) All the 'hypothetical proteins' were checked, and non-coding ORFs recognized by the Z curve method were removed. (ii) The translation initiation sites (TISs) of 20% ~ 25% of all the protein-coding genes have been corrected based on the NCBI RefSeq, ProTISA database and an ab initio program, GS-Finder. (iii) Potential functions of about 10% 'hypothetical proteins' have been predicted using sequence alignment tools. (iv) Two theoretical gene expression indices, the codon adaptation index (CAI) and the E(g) index, were calculated to predict the gene expression levels. (v) Potential agricultural bactericide targets and their homology-modeled 3D structures are provided in the database, which is of significance for agricultural antibiotic discovery.

Conclusion
The results in DIGAP provide useful information for understanding the pathogenetic mechanisms of phytopathogens and for finding agricultural bactericides. DIGAP is freely available at http://ibi.hzau.edu.cn/digap/.
Persistent, triple-virus co-infections in mosquito cells
Authors: Kanthong Nipaporn , Khemnu Nuanpan , Pattanakitsakul Sa-Nga , Malasit Prida , Flegel Timothy W 
Published: January 2010

Abstract

Background
It is known that insects and crustaceans can carry simultaneous, active infections of two or more viruses without showing signs of disease, but it was not clear whether co-infecting viruses occupied the same cells or different cells in common target tissues. Our previous work showed that successive challenge of mosquito cell cultures followed by serial, split-passage resulted in stabilized cultures with 100% of the cells co-infected with Dengue virus (DEN) and an insect parvovirus (densovirus) (DNV). By addition of Japanese encephalitis virus (JE), we tested our hypothesis that stable, persistent, triple-virus co-infections could be obtained by the same process.

Results
Using immunocytochemistry by confocal microscopy, we found that JE super-challenge of cells dually infected with DEN and DNV resulted in stable cultures without signs of cytopathology, and with 99% of the cells producing antigens of the 3 viruses. Location of antigens for all 3 viruses in the triple co-infections was dominant in the cell nuclei. Except for DNV, this differed from the distribution in cells persistently infected with the individual viruses or co-infected with DNV and DEN. The dependence of viral antigen distribution on single infection or co-infection status suggested that host cells underwent an adaptive process to accommodate 2 or more viruses.

Conclusions
Individual mosquito cells can accommodate at least 3 viruses simultaneously in an adaptive manner. The phenomenon provides an opportunity for genetic exchange between diverse viruses and it may have important medical and veterinary implications for arboviruses.
Bicarbonate enhances expression of the endocarditis and biofilm associated pilus locus, ebpR-ebpABC, in Enterococcus faecalis
Authors: Bourgogne Agathe , Thomson L Charlene , Murray Barbara E 
Published: January 2010

Abstract

Background
We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis
e ndocarditis and b iofilm associated p ilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation of the ebpR-ebpABC locus in virulence. However, there is no report relating to the environmental conditions that affect expression of the ebpR-ebpABC locus.

Results
In this study, we examined the effect of CO2/HCO3
-, pH, and the Fsr system on the ebpR-ebpABC locus expression. The presence of 5% CO2/0.1 M HCO3
- increased ebpR-ebpABC expression, while the Fsr system was confirmed to be a weak repressor of this locus. The mechanism by which the Fsr system repressed the ebpR-ebpABC locus expression appears independent of the effects of CO2
- bicarbonate. Furthermore, by using an ebpA::lacZ fusion as a reporter, we showed that addition of 0.1 M sodium bicarbonate to TSBG (buffered at pH 7.5), but not the presence of 5% CO2, induced ebpA expression in TSBG broth. In addition, using microarray analysis, we found 73 genes affected by the presence of sodium bicarbonate (abs(fold) > 2, P < 0.05), the majority of which belong to the PTS system and ABC transporter families. Finally, pilus production correlated with ebpA mRNA levels under the conditions tested.

Conclusions
This study reports that the ebp locus expression is enhanced by the presence of bicarbonate with a consequential increase in the number of cells producing pili. Although the molecular basis of the bicarbonate effect remains unclear, the pathway is independent of the Fsr system. In conclusion, E. faecalis joins the growing family of pathogens that regulates virulence gene expression in response to bicarbonate and/or CO2.