bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses
Authors: Travanty Emily , Zhou Bin , Zhang Hongbo , Di Y. Peter , Alcorn John F. , Wentworth David E. , Mason Robert , Wang Jieru 
Published: September 2015

ABSTRACT
Human alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection.

IMPORTANCE
Disease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection.
Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a DynamicIn VitroModel
Authors: Spiesschaert Bart , Goldenbogen Björn , Taferner Selina , Schade Matthias , Mahmoud Medhat , Klipp Edda , Osterrieder Nikolaus , Azab Walid 
Published: September 2015

ABSTRACTInfected peripheral blood mononuclear cells (PBMC) effectively transport equine herpesvirus type 1 (EHV-1), but not EHV-4, to endothelial cells (EC) lining the blood vessels of the pregnant uterus or central nervous system, a process that can result in abortion or myeloencephalopathy. We examined, using a dynamicin vitromodel, the differences between EHV-1 and EHV-4 infection of PBMC and PBMC-EC interactions. In order to evaluate viral transfer between infected PBMC and EC, cocultivation assays were performed. Only EHV-1 was transferred from PBMC to EC, and viral glycoprotein B (gB) was shown to be mainly responsible for this form of cell-to-cell transfer. For addressing the more dynamic aspects of PBMC-EC interaction, infected PBMC were perfused through a flow channel containing EC in the presence of neutralizing antibodies. By simulating capillary blood flow and analyzing the behavior of infected PBMC through live fluorescence imaging and automated cell tracking, we observed that EHV-1 was able to maintain tethering and rolling of infected PBMC on EC more effectively than EHV-4. Deletion of US3 reduced the ability of infected PBMC to tether and roll compared to that of cells infected with parental virus, which resulted in a significant reduction in virus transfer from PBMC to EC. Taking the results together, we conclude that systemic spread and EC infection by EHV-1, but not EHV-4, is caused by its ability to infect and/or reprogram mononuclear cells with respect to their tethering and rolling behavior on EC and consequent virus transfer.IMPORTANCEEHV-1 is widespread throughout the world and causes substantial economic losses through outbreaks of respiratory disease, abortion, and myeloencephalopathy. Despite many years of research, no fully protective vaccines have been developed, and several aspects of viral pathogenesis still need to be uncovered. In the current study, we investigated the molecular mechanisms that facilitate the cell-associated viremia, which is arguably the most important aspect of EHV-1 pathogenesis. The newly discovered functions of gB and pUS3 add new facets to their previously reported roles. Due to the conserved nature of cell-associated viremia among numerous herpesviruses, these results are also very relevant for viruses such as varicella-zoster virus, pseudorabies virus, human cytomegalovirus, and others. In addition, the constructed mutant and recombinant viruses exhibit potentin vitroreplication but have significant defects in certain stages of the disease course. These viruses therefore show much promise as candidates for future live vaccines.
Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5
Authors: Yang Yang , Zengel James , Sun Minghao , Sleeman Katrina , Timani Khalid Amine , Aligo Jason , Rota Paul , Wu Jianguo , He Biao 
Published: September 2015

ABSTRACT
Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the N-terminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses.

IMPORTANCE
We identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the rational design of vaccines and potential antiviral drugs.
Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus
Authors: Medaglia Maria Luiza G. , Moussatché Nissin , Nitsche Andreas , Dabrowski Pjotr Wojtek , Li Yu , Damon Inger K. , Lucas Carolina G. O. , Arruda Luciana B. , Damaso Clarissa R. 
Published: September 2015

ABSTRACT

Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV;
Poxviridae
). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain.

IMPORTANCE
First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the search for new-generation smallpox vaccines that combine low pathogenicity, immune protection, and genetic homogeneity is extremely important. In addition, the phylogenetic relationships and origins of VACV strains are quite nebulous. We show the characterization of two clones of VACV-IOC, a unique smallpox vaccine strain that contributed to smallpox eradication in Brazil. The immunogenicity and reduced virulence make the IOC clones good options for alternative second-generation smallpox vaccines. More importantly, this study reveals the phylogenetic relationship between VACV-IOC, feral VACV established in nature, and the ancestor-like horsepox virus. Our data expand the discussion on the origins and evolutionary connections of VACV lineages.
A Population Genetics Perspective on Geminivirus Infection
Authors: Weigel Karin , Pohl Jens O. , Wege Christina , Jeske Holger 
Published: September 2015

ABSTRACT

The selective accumulation of both DNA components of a bipartite geminivirus,
Abutilon
mosaic virus, was recorded during early systemic infection of
Nicotiana benthamiana
plants. Purified nuclei were diagnosed for viral DNA using hybridization specific for DNA A or DNA B to detect these individual genome components either alone or both simultaneously by dual-color staining. Although this virus needs both components for symptomatic infection, DNA A alone was transported to upper leaves, where it was imported into phloem nuclei and replicated autonomously. The coinfection with DNA A and DNA B revealed an independent spread of both molecules, which resulted in a stochastic distribution of DNA A- and DNA A/B-infected nuclei. A population genetics evaluation of the respective frequencies was compared to a model computation. This elucidated a surprisingly simple relationship between the initial frequencies of the viral DNA components and the number of susceptible cells during the course of early systemic infection.

IMPORTANCE
For bipartite begomoviruses, DNA B-independent long-distance spread of DNA A has been described before, but it has never been shown whether viral DNA A alone invades nuclei of systemic tissues and replicates therein. This is demonstrated now for the first time. During infection with DNA A and DNA B, a similar solitary spread of DNA A can be recognized at early stages. We describe a population genetics model of how the hit probabilities of DNA A and DNA B for susceptible cells determine the relative frequencies of either genome component during the course of infection.
Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference
Authors: Taylor Justin K. , Coleman Christopher M. , Postel Sandra , Sisk Jeanne M. , Bernbaum John G. , Venkataraman Thiagarajan , Sundberg Eric J. , Frieman Matthew B. 
Published: September 2015

ABSTRACT

Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an
in vitro
screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PL
Pro
), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2.

IMPORTANCE
The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.
Cell Walls and the Convergent Evolution of the Viral Envelope
Authors: Buchmann Jan P. , Holmes Edward C. 
Published: September 2015

SUMMARYWhy some viruses are enveloped while others lack an outer lipid bilayer is a major question in viral evolution but one that has received relatively little attention. The viral envelope serves several functions, including protecting the RNA or DNA molecule(s), evading recognition by the immune system, and facilitating virus entry. Despite these commonalities, viral envelopes come in a wide variety of shapes and configurations. The evolution of the viral envelope is made more puzzling by the fact that nonenveloped viruses are able to infect a diverse range of hosts across the tree of life. We reviewed the entry, transmission, and exit pathways of all (101) viral families on the 2013 International Committee on Taxonomy of Viruses (ICTV) list. By doing this, we revealed a strong association between the lack of a viral envelope and the presence of a cell wall in the hosts these viruses infect. We were able to propose a new hypothesis for the existence of enveloped and nonenveloped viruses, in which the latter represent an adaptation to cells surrounded by a cell wall, while the former are an adaptation to animal cells where cell walls are absent. In particular, cell walls inhibit viral entry and exit, as well as viral transport within an organism, all of which are critical waypoints for successful infection and spread. Finally, we discuss how this new model for the origin of the viral envelope impacts our overall understanding of virus evolution.
Electroacupuncture Ameliorates Cognitive Impairment and Regulates the Expression of Apoptosis-Related Genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury
Authors: Liu Fang , Jiang Yi-Jing , Zhao Hong-Jia , Yao Li-Qun , Chen Li-Dian 
Published: September 2015

Background Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. Objective To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Methods Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. Results The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13±4.30% vs 38.40±3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61±0.19 vs 0.50±0.05, p<0.01). Conclusions These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.
Do neighbourhood socioeconomic circumstances not matter for weight status among Australian men? Multilevel evidence from a household survey of 14 691 adults
Authors: Feng Xiaoqi , Wilson Andrew 
Published: September 2015

ObjectiveA recent analysis of the Australian National Health Survey (2011–2012) reported that the patterning of overweight and obesity among men, unlike for women, was not associated with neighbourhood socioeconomic disadvantage. The purpose of this study was to examine whether this gender difference in potential neighbourhood ‘effects’ on adult weight status can be observed in analyses of a different source of data.Design, setting and participantsA cross-sectional sample of 14 693 people aged 18 years or older was selected from the 2012 wave of the ‘Household, Income and Labour Dynamics in Australia’ (HILDA). Three person-level outcomes were considered: (1) body mass index (BMI); (2) a binary indicator of ‘normal weight’ versus ‘overweight or obese’; and (3) ‘normal weight or overweight’ versus ‘obese’. Area-level socioeconomic circumstances were measured using quintiles of the Socio Economic Index For Areas (SEIFA). Multilevel linear and logistic regression models were used to examine associations while accounting for clustering within households and neighbourhoods, adjusting for person-level socioeconomic confounders.ResultsNeighbourhood-level factors accounted for 4.9% of the overall variation in BMI, whereas 20.1% was attributable to household-level factors. Compared with their peers living in deprived neighbourhoods, mean BMI was 0.7 kg/m2lower among men and 2.2 kg/m2lower among women living in affluent areas, with a clear trend across categories. Similarly, the percentage of overweight and obese, and obesity specifically, was lower in affluent areas for both men and women. These results were robust to adjustment for confounders.ConclusionsUnlike findings from the national health survey, but in line with evidence from other high-income countries, this study finds an inverse patterning of BMI by neighbourhood disadvantage for men, and especially among women. The potential mediators which underpin this gender difference in BMI within disadvantaged neighbourhoods warrant further investigation.
Missed nursing care is linked to patient satisfaction: a cross-sectional study of US hospitals
Authors: Lake Eileen T , Germack Hayley D , Viscardi Molly Kreider 
Published: September 2015

BackgroundAs nurses are the principal care provider in the hospital setting, the completion or omission of nursing care is likely to have a sizable impact on the patient care experience. However, this relationship has not been explored empirically.AimTo describe the prevalence and patterns of missed nursing care and explore their relationship to the patient care experience.MethodsThis cross-sectional study used secondary nurse and patient survey data from 409 adult non-federal acute care US hospitals in four states. Descriptive statistics were calculated and linear regression models were conducted at the hospital level. Regression models included controls for hospital structural characteristics.ResultsIn an average hospital, nurses missed 2.7 of 12 required care activities per shift. Three-fourths (73.4%) of nurses reported missing at least one activity on their last shift. This percentage ranged from 25 to 100 across hospitals. Nurses most commonly reported not being able to comfort or talk with patients (47.6%) and plan care (38.5%). 6 out of 10 patients rated hospitals highly. This proportion ranged from 33% to 90% across hospitals. At hospitals where nurses missed more care (1 SD higher=0.74 items), 2.2% fewer patients rated the hospital highly (p<0.001); a coefficient equivalent to a one-quarter SD change.ConclusionsMissed nursing care is common in US hospitals and varies widely. Most patients rate their hospital care experience highly, but this also varies widely across hospitals. Patients have poorer care experiences in hospitals where more nurses miss required nursing care. Supporting nurses’ ability to complete required care may optimise the patient care experience. As hospitals face changing reimbursement landscapes, ensuring adequate nursing resources should be a top priority.