bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid Vector-Linked Maturation of Natural Killer (NK) Cells Is Coupled to Antigen-Dependent NK Cell Activation during DNA-Based Immunization in Mice
Authors: Zhu Ren , Mancini-Bourgine Maryline , Zhang Xiao Ming , Bayard Florence , Deng Qiang , Michel Marie-Louise 
Published: July 2011

ABSTRACTPlasmid DNA vaccines serve in a wide array of applications ranging from prophylactic vaccines to potential therapeutic tools against infectious diseases and cancer. In this study, we analyzed the mechanisms underlying the activation of natural killer (NK) cells and their potential role in adaptive immunity during DNA-based immunization against hepatitis B virus surface antigen in mice. We observed that the mature Mac-1+CD27−NK cell subset increased in the liver of mice early after DNA injection, whereas the number of the less mature Mac-1+CD27+NK cells in the liver and spleen was significantly reduced. This effect was attributed to bacterial sequences present in the plasmid backbone rather than to the encoded antigen and was not observed in immunized MyD88-deficient mice. The activation of NK cells by plasmid-DNA injection was associated with an increase in their effector functions that depended on the expressed antigen. Maturation of NK cells was abrogated in the absence of T cells, suggesting that cross talk exists between NK cells and antigen-specific T cells. Taken together, our data unravel the mechanics of plasmid vector-induced maturation of NK cells and plasmid-encoded antigen-dependent activation of NK cells required for a crucial role of NK cells in DNA vaccine-induced immunogenicity.
Artificial Recombination May Influence the Evolutionary Analysis of Newcastle Disease Virus
Authors: Song Qingqing , Cao Yongzhong , Li Qun , Gu Min , Zhong Lei , Hu Shunlin , Wan Hongquan , Liu Xiufan 
Published: July 2011

ABSTRACT
The recombination rate in Newcastle disease virus (NDV) was as high as 10% in RDP analysis with full-length NDV genome sequences available in GenBank. We found that two NDV strains, China/Guangxi09/2003 and NDV/03/018, previously reported as recombinants, failed to show any evidence of recombination upon complete genome resequencing. Furthermore, we were able to reproduce artificial recombination by amplification of the M gene in a mixed sample of strains LaSota and ZJ1. It appears that the recombination of NDV is not as common as has been reported. NDV sequences in GenBank should be analyzed with caution during bioinformatic analyses for natural recombination events.
Evasion and Subversion of Interferon-Mediated Antiviral Immunity by Kaposi's Sarcoma-Associated Herpesvirus: an Overview
Authors: Sathish Narayanan , Yuan Yan 
Published: July 2011

ABSTRACT

Viral invasion of a host cell triggers immune responses with both innate and adaptive components. The innate immune response involving the induction of type I interferons (alpha and beta interferons [IFN-α and -β]) constitutes the first line of antiviral defenses. The type I IFNs signal the transcription of a group of antiviral effector proteins, the IFN-stimulated genes (ISGs), which target distinct viral components and distinct stages of the viral life cycle, aiming to eliminate invading viruses. In the case of Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma (KS), a sudden upsurge of type I IFN-mediated innate antiviral signals is seen immediately following both primary
de novo
infection and viral lytic reactivation from latency. Potent subversion of these responses thus becomes mandatory for the successful establishment of a primary infection following viral entry as well as for efficient viral assembly and egress. This review gives a concise overview of the induction of the type I IFN signaling pathways in response to viral infection and provides a comprehensive understanding of the antagonizing effects exerted by KSHV on type I IFN pathways wielded at various stages of the viral life cycle. Information garnered from this review should result in a better understanding of KSHV biology essential for the development of immunotherapeutic strategies targeted toward KSHV-associated malignancies.
Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication
Authors: Pudupakam R. S. , Kenney Scott P. , Córdoba Laura , Huang Yao-Wei , Dryman Barbara A. , LeRoith Tanya , Pierson F. William , Meng Xiang-Jin 
Published: July 2011

ABSTRACT

The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity
in vitro
, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.
The
TRIM5
Gene Modulates Penile Mucosal Acquisition of Simian Immunodeficiency Virus in Rhesus Monkeys
Authors: Yeh Wendy W. , Rao Srinivas S. , Lim So-Yon , Zhang Jinrong , Hraber Peter T. , Brassard Laura M. , Luedemann Corinne , Todd John Paul , Dodson Alan , Shen Ling , Buzby Adam P. , Whitney James B. , Korber Bette T. , Nabel Gary J. , Mascola John R. , Letvin Norman L. 
Published: July 2011

ABSTRACT

There is considerable variability in host susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, but the host genetic determinants of that variability are not well understood. In addition to serving as a block for cross-species retroviral infection,
TRIM5
was recently shown to play a central role in limiting primate immunodeficiency virus replication. We hypothesized that
TRIM5
may also contribute to susceptibility to mucosal acquisition of simian immunodeficiency virus (SIV) in rhesus monkeys. We explored this hypothesis by establishing 3 cohorts of Indian-origin rhesus monkeys with different
TRIM5
genotypes: homozygous restrictive, heterozygous permissive, and homozygous permissive. We then evaluated the effect of
TRIM5
genotype on the penile transmission of SIVsmE660. We observed a significant effect of
TRIM5
genotype on mucosal SIVsmE660 acquisition in that no SIV transmission occurred in monkeys with only restrictive
TRIM5
alleles. In contrast, systemic SIV infections were initiated after preputial pocket exposures in monkeys that had at least one permissive
TRIM5
allele. These data demonstrate that host genetic factors can play a critical role in restricting mucosal transmission of a primate immunodeficiency virus. In addition, we used our understanding of
TRIM5
to establish a novel nonhuman primate penile transmission model for AIDS mucosal pathogenesis and vaccine research.
Interaction between Geminivirus Replication Protein and the SUMO-Conjugating Enzyme Is Required for Viral Infection
Authors: Sánchez-Durán Miguel A. , Dallas Mary B. , Ascencio-Ibañez José T. , Reyes Maria Ines , Arroyo-Mateos Manuel , Ruiz-Albert Javier , Hanley-Bowdoin Linda , Bejarano Eduardo R. 
Published: July 2011

ABSTRACT
Geminiviruses are small DNA viruses that replicate in nuclei of infected plant cells by using plant DNA polymerases. These viruses encode a protein designated AL1, Rep, or AC1 that is essential for viral replication. AL1 is an oligomeric protein that binds to double-stranded DNA, catalyzes the cleavage and ligation of single-stranded DNA, and induces the accumulation of host replication machinery. It also interacts with several host proteins, including the cell cycle regulator retinoblastoma-related protein (RBR), the DNA replication protein PCNA (proliferating cellular nuclear antigen), and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme [SCE1]). The SCE1-binding motif was mapped by deletion to a region encompassing AL1 amino acids 85 to 114. Alanine mutagenesis of lysine residues in the binding region either reduced or eliminated the interaction with SCE1, but no defects were observed for other AL1 functions, such as oligomerization, DNA binding, DNA cleavage, and interaction with AL3 or RBR. The lysine mutations reduced or abolished virus infectivity in plants and viral DNA accumulation in transient-replication assays, suggesting that the AL1-SCE1 interaction is required for viral DNA replication. Ectopic AL1 expression did not result in broad changes in the sumoylation pattern of plant cells, but specific changes were detected, indicating that AL1 modifies the sumoylation state of selected host proteins. These results established the importance of AL1-SCE1 interactions during geminivirus infection of plants and suggested that AL1 alters the sumoylation of selected host factors to create an environment suitable for viral infection.
An Externalized Polypeptide Partitions between Two Distinct Sites on Genome-Released Poliovirus Particles
Authors: Lin Jun , Cheng Naiqian , Chow Marie , Filman David J. , Steven Alasdair C. , Hogle James M. , Belnap David M. 
Published: July 2011

ABSTRACT
During cell entry, native poliovirus (160S) converts to a cell-entry intermediate (135S) particle, resulting in the externalization of capsid proteins VP4 and the amino terminus of VP1 (residues 1 to 53). Externalization of these entities is followed by release of the RNA genome (uncoating), leaving an empty (80S) particle. The antigen-binding fragment (Fab) of a monospecific peptide 1 (P1) antibody, which was raised against a peptide corresponding to amino-terminal residues 24 to 40 of VP1, was utilized to track the location of the amino terminus of VP1 in the 135S and 80S states of poliovirus particles via cryogenic electron microscopy (cryo-EM) and three-dimensional image reconstruction. On 135S, P1 Fabs bind to a prominent feature on the external surface known as the “propeller tip.” In contrast, our initial 80S-P1 reconstruction showed P1 Fabs also binding to a second site, at least 50 Å distant, at the icosahedral 2-fold axes. Further analysis showed that the overall population of 80S-P1 particles consisted of three kinds of capsids: those with P1 Fabs bound only at the propeller tips, P1 Fabs bound only at the 2-fold axes, or P1 Fabs simultaneously bound at both positions. Our results indicate that, in 80S particles, a significant fraction of VP1 can deviate from icosahedral symmetry. Hence, this portion of VP1 does not change conformation synchronously when switching from the 135S state. These conclusions are compatible with previous observations of multiple conformations of the 80S state and suggest that movement of the amino terminus of VP1 has a role in uncoating. Similar deviations from icosahedral symmetry may be biologically significant during other viral transitions.
A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress
Authors: Maric Martina , Shao Jianqiang , Ryan Randi J. , Wong Chun-Shu , Gonzalez-Alegre Pedro , Roller Richard J. 
Published: July 2011

ABSTRACT
Herpes simplex virus 1 (HSV-1) capsids leave the nucleus by a process of envelopment and de-envelopment at the nuclear envelope (NE) that is accompanied by structural alterations of the NE. As capsids translocate across the NE, transient primary enveloped virions form in the perinuclear space. Here, we provide evidence that torsinA (TA), a ubiquitously expressed ATPase, has a role in HSV-1 nuclear egress. TA resides within the lumen of the endoplasmic reticulum (ER)/NE and functions in maintaining normal NE architecture. We show that perturbation of TA normal function by overexpressing torsinA wild type (TAwt) inhibits HSV-1 production. Ultrastructural analysis of infected cells overexpressing TAwt revealed reduced levels of surface virions in addition to accumulation of novel, double-membrane structures called virus-like vesicles (VLVs). Although mainly found in the cytoplasm, VLVs resemble primary virions in their size, by the appearance of the inner membrane, and by the presence of pUL34, a structural component of primary virions. Collectively, our data suggest a model in which interference of TA normal function by overexpression impairs de-envelopment of the primary virions leading to their accumulation in a cytoplasmic membrane compartment. This implies novel functions for TA at the NE.
T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome
Authors: Hammerbeck Christopher D. , Hooper Jay W. 
Published: July 2011

ABSTRACTAndes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology.
High Prevalence of Simian Immunodeficiency Virus Infection in a Community of Savanna Chimpanzees
Authors: Rudicell Rebecca S. , Piel Alex K. , Stewart Fiona , Moore Deborah L. , Learn Gerald H. , Li Yingying , Takehisa Jun , Pintea Lilian , Shaw George M. , Moore Jim , Sharp Paul M. , Hahn Beatrice H. 
Published: July 2011

ABSTRACT

Simian immunodeficiency virus of chimpanzees (SIVcpz) has a significant negative impact on the health, reproduction, and life span of chimpanzees, yet the prevalence and distribution of this virus in wild-living populations are still only poorly understood. Here, we show that savanna chimpanzees, who live in ecologically marginal habitats at 10- to 50-fold lower population densities than forest chimpanzees, can be infected with SIVcpz at high prevalence rates. Fecal samples were collected from nonhabituated eastern chimpanzees (
Pan troglodytes schweinfurthii
) in the Issa Valley (
n
= 375) and Shangwa River (
n
= 6) areas of the Masito-Ugalla region in western Tanzania, genotyped to determine the number of sampled individuals, and tested for SIVcpz-specific antibodies and nucleic acids. None of 5 Shangwa River apes tested positive for SIVcpz; however, 21 of 67 Issa Valley chimpanzees were SIVcpz infected, indicating a prevalence rate of 31% (95% confidence interval, 21% to 44%). Two individuals became infected during the 14-month observation period, documenting continuing virus spread in this community. To characterize the newly identified SIVcpz strains, partial and full-length viral sequences were amplified from fecal RNA of 10 infected chimpanzees. Phylogenetic analyses showed that the Ugalla viruses formed a monophyletic lineage most closely related to viruses endemic in Gombe National Park, also located in Tanzania, indicating a connection between these now separated communities at some time in the past. These findings document that SIVcpz is more widespread in Tanzania than previously thought and that even very low-density chimpanzee populations can be infected with SIVcpz at high prevalence rates. Determining whether savanna chimpanzees, who face much more extreme environmental conditions than forest chimpanzees, are more susceptible to SIVcpz-associated morbidity and mortality will have important scientific and conservation implications.
Mortality in carotid sinus hypersensitivity: a cohort study
Authors: Hampton Joanna L , Brayne Carol , Bradley Michelle , Kenny Rose Anne 
Published: July 2011

ObjectiveCarotid sinus hypersensitivity (CSH) is common in older people. The authors hypothesise that patients with CSH have a higher mortality than a geographically, age-matched older cohort.DesignA retrospective cohort study compared to geographical and age-matched data from the Office of National Statistics.SettingSpecialist clinic in tertiary centre.Patients1504 patients with CSH were identified from a single syncope outpatient assessment service between 1990 and 2001.InterventionsVital status was confirmed, and death certificates were sought for all deceased patients up to 2003.Main outcome measuresKaplan–Meier survival curves were analysed within the cohort according to three different subtypes of CSH. Standardised mortality rates (SMRs) were determined using geographical and age-matched data from the Office of National Statistics.ResultsThere was no difference between CSH patients and the general population in SMRs for all causes, or for cerebrovascular or cardiovascular deaths. There was no difference in survival between the three subtypes of CSH (p=0.2) within the study cohort.ConclusionCSH is not associated with a higher mortality than the general population, and there are no differences in mortality between the three subtypes of CSH. This confirms earlier findings and reinforces the neutral effect of CSH on mortality.
Clinical and epidemiological profile of patients with severe H1N1/09 pandemic influenza in Australia and New Zealand: an observational cohort study
Authors: Cheng Allen C , Kotsimbos Tom , Reynolds Anna , Bowler Simon D , Brown Simon G A , Hancox Robert J , Holmes Mark , Irving Louis , Jenkins Christine , Thompson Philip , Simpson Graham , Waterer Grant , Wood-Baker Richard , Kelly Paul M 
Published: July 2011

BackgroundPandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity.MethodsThe authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand.ResultsDuring the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza.ConclusionsThe clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.
PRESIDIO
Authors: You Lawrence L. , Pollack Kristal T. , Long Darrell D. E. , Gopinath K. 
Published: July 2011

The ever-increasing volume of archival data that needs to be reliably retained for long periods of time and the decreasing costs of disk storage, memory, and processing have motivated the design of low-cost, high-efficiency disk-based storage systems. However,
managed
disk storage is still expensive. To further lower the cost, redundancy can be eliminated with the use of interfile and intrafile data compression. However, it is not clear what the optimal strategy for compressing data is, given the diverse collections of data.

To create a scalable archival storage system that efficiently stores diverse data, we present PRESIDIO, a framework that selects from different space-reduction efficent storage methods (ESMs) to detect similarity and reduce or eliminate redundancy when storing objects. In addition, the framework uses a virtualized content addressable store (VCAS) that hides from the user the complexity of knowing which space-efficient techniques are used, including chunk-based deduplication or delta compression. Storing and retrieving objects are polymorphic operations independent of their content-based address. A new technique, harmonic super-fingerprinting, is also used for obtaining successively more accurate (but also more costly) measures of similarity to identify the existing objects in a very large data set that are most similar to an incoming new object.
The PRESIDIO design, when reported earlier, had comprehensively introduced for the first time the notion of deduplication, which is now being offered as a service in storage systems by major vendors. As an aid to the design of such systems, we evaluate and present various parameters that affect the efficiency of a storage system using empirical data.