bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feline Leukemia Virus Infection Requires a Post-Receptor Binding Envelope-Dependent Cellular Component
Authors: Hussain Naveen , Thickett Kelly R. , Na Hong , Leung Cherry , Tailor Chetankumar S. 
Published: September 2011

ABSTRACT

Gammaretrovirus receptors have been suggested to contain the necessary determinants to mediate virus binding and entry. Here, we show that murine NIH 3T3 and baby hamster kidney (BHK) cells overexpressing receptors for subgroup A, B, and C feline leukemia viruses (FeLVs) are weakly susceptible (10
1
to 10
2
CFU/ml) to FeLV pseudotype viruses containing murine leukemia virus (MLV) core (Gag-Pol) proteins, whereas FeLV receptor-expressing murine
Mus dunni
tail fibroblast (MDTF) cells are highly susceptible (10
4
to 10
6
CFU/ml). However, NIH 3T3 cells expressing the FeLV subgroup B receptor PiT1 are highly susceptible to gibbon ape leukemia virus pseudotype virus, which differs from the FeLV pseudotype viruses only in the envelope protein. FeLV resistance is not caused by a defect in envelope binding, low receptor expression levels, or N-linked glycosylation. Resistance is not alleviated by substitution of the MLV core in the FeLV pseudotype virus with FeLV core proteins. Interestingly, FeLV resistance is alleviated by fusion of receptor-expressing NIH 3T3 and BHK cells with MDTF or human TE671 cells, suggesting the absence of an additional cellular component in NIH 3T3 and BHK cells that is required for FeLV infection. The putative FeLV-specific cellular component is not a secreted factor, as MDTF conditioned medium does not alleviate the block to FeLV infection. Together, our findings suggest that FeLV infection requires an additional envelope-dependent cellular component that is absent in NIH 3T3 and BHK cells but that is present in MDTF and TE671 cells.
Antibody-Mediated Enhancement of HIV-1 and HIV-2 Production from BST-2/Tetherin-Positive Cells
Authors: Miyagi Eri , Andrew Amy , Kao Sandra , Yoshida Takeshi , Strebel Klaus 
Published: September 2011

ABSTRACT

BST-2/CD317/HM1.24/tetherin is a B-cell antigen overexpressed on the surface of myeloma cell lines and on neoplastic plasma cells of patients with multiple myeloma. Antibodies to BST-2 are in clinical trial for the treatment of multiple myeloma and are considered for the treatment of solid tumors with high BST-2 antigen levels. Functionally, BST-2 restricts the secretion of retroviruses, including human immunodeficiency virus type 1, as well as members of the herpesvirus, filovirus, and arenavirus families, presumably by tethering nascent virions to the cell surface. Here we report that BST-2 antibody treatment facilitates virus release from BST-2
+
cells by interfering with the tethering activity of BST-2. BST-2 antibodies were unable to release already tethered virions and were most effective when added early during virus production. BST-2 antibody treatment did not affect BST-2 dimerization and did not reduce the cell surface expression of BST-2. Interestingly, BST-2 antibody treatment reduced the nonspecific shedding of BST-2 and limited the encapsidation of BST-2 into virions. Finally, flotation analyses indicate that BST-2 antibodies affect the distribution of BST-2 within membrane rafts. Our data suggest that BST-2 antibody treatment may enhance virus release by inducing a redistribution of BST-2 at the cell surface, thus preventing it from accumulating at the sites of virus budding.
Characterization of the Human CD8+T Cell Response following Infection with 2009 Pandemic Influenza H1N1 Virus
Authors: Hillaire M. L. B. , van Trierum S. E. , Bodewes R. , van Baalen C. A. , van Binnendijk R. S. , Koopmans M. P. , Fouchier R. A. M. , Osterhaus A. D. M. E. , Rimmelzwaan G. F. 
Published: September 2011

ABSTRACTThe 2009 H1N1 influenza pandemic provided an opportunity to study human virus-specific T cell responses after infection with a novel influenza virus against which limited humoral immunity existed in the population. Here we describe the magnitude, kinetics, and nature of the virus-specific T cell response using intracellular gamma interferon (IFN-γ) staining and fluorochrome-labeled major histocompatibility complex (MHC) class I-peptide complexes. We demonstrate that influenza virus-infected patients develop recall T cell responses that peak within 1 week postinfection and that contract rapidly. In particular, effector cell frequencies declined rapidly postinfection in favor of relatively larger proportions of central memory cells.
Gamma Interferon and Perforin Control the Strength, but Not the Hierarchy, of Immunodominance of an Antiviral CD8+T Cell Response
Authors: Remakus Sanda , Sigal Luis J. 
Published: September 2011

ABSTRACTThe two major antiviral effector mechanisms of CD8+T cells are thought to be perforin (Prf)-mediated cell lysis and gamma interferon (IFN-γ)-mediated induction of an antiviral state. By affecting the expression of proteins involved in antigen presentation, IFN-γ is also thought to shape the magnitude and specificity of the CD8+T cell response. Here we studied the roles of Prf and IFN-γ in shaping the effector and memory CD8+T cell responses to vaccinia virus (VACV). IFN-γ deficiency resulted in increased numbers of anti-VACV effector and memory CD8+T cells, which were partly dependent on increased virus loads. On the other hand, Prf-deficient mice showed an increase in the number of VACV-specific CD8+T cells only in the memory phase. Treatment of the mice with the antiviral drug cidofovir reduced the numbers of effector and memory cells closer to wild-type levels in IFN-γ-deficient mice and reduced the numbers of memory CD8+T cells to wild-type levels in Prf-deficient mice. These data suggest that virus loads are the main reason for the increased strength of the CD8 response in IFN-γ- and Prf-deficient mice. Neither Prf deficiency nor IFN-γ deficiency had an effect on the immunodominance hierarchy of five Kb-restricted CD8+T cell determinants either during acute infection or after recovery. Thus, our work shows that CD8+T cell immunodominance during VACV infection is not affected by the effects of IFN-γ on the antigen presentation machinery.
Durable Mucosal Simian Immunodeficiency Virus-Specific Effector Memory T Lymphocyte Responses Elicited by Recombinant Adenovirus Vectors in Rhesus Monkeys
Authors: Li Hualin , Liu Jinyan , Carville Angela , Mansfield Keith G. , Lynch Diana , Barouch Dan H. 
Published: September 2011

ABSTRACTThe induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. In particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. Here we report that intramuscular injection of nonreplicating recombinant adenovirus (rAd) vectors into rhesus monkeys induced remarkably durable simian immunodeficiency virus (SIV)-specific T lymphocyte responses that persisted for over 2 years in both peripheral blood and multiple mucosal tissues, including colorectal, duodenal, and vaginal biopsy specimens, as well as bronchoalveolar lavage fluid. In peripheral blood, SIV-specific T lymphocytes underwent the expected phenotypic evolution from effector memory T cells (TEM) to central memory T cells (TCM) following vaccination. In contrast, mucosal SIV-specific T lymphocytes exhibited a persistent and durable TEMphenotype that did not evolve over time. These data demonstrate that nonreplicating rAd vectors induce durable and widely distributed effector memory mucosal T lymphocyte responses that are phenotypically distinct from peripheral T lymphocyte responses. Vaccine-elicited TEMresponses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry.
Human Cytomegalovirus Primase UL70 Specifically Interacts with Cellular Factor Snapin
Authors: Shen Ao , Lei Ji , Yang Edward , Pei Yonggang , Chen Yuan-Chuan , Gong Hao , Xiao Gengfu , Liu Fenyong 
Published: September 2011

ABSTRACT
Genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV). HCMV UL70 is believed to encode the primase of the DNA replication machinery, a function which requires localization in the nucleus, the site of viral DNA synthesis. No host factors that interact with UL70 have been reported. In this study, we provide the first direct evidence that UL70 specifically interacts with Snapin, a human protein that is predominantly localized in the cytoplasm and is associated with cellular vesicles. The interaction between UL70 and Snapin was identified in both the two-hybrid screen in yeast and coimmunoprecipitation in human cells. The nuclear import of UL70 was decreased in cells overexpressing Snapin and increased in cells in which the expression of Snapin was downregulated with anti-Snapin small interfering RNA (siRNA) molecules, respectively. Furthermore, viral DNA synthesis and progeny production were decreased in cells overexpressing Snapin and increased in the anti-Snapin siRNA-treated cells, respectively. In contrast, no significant difference in the nuclear level of UL70, viral DNA synthesis, and progeny production was found among the parental cells and cells that either expressed a control empty vector or were treated with control siRNA molecules that did not recognize any viral or cellular transcripts. Our results suggest that Snapin may play a key role in regulating the cellular localization of UL70 in HCMV, leading to modulation of viral DNA synthesis and progeny production.
Systems Virology Identifies a Mitochondrial Fatty Acid Oxidation Enzyme, Dodecenoyl Coenzyme A Delta Isomerase, Required for Hepatitis C Virus Replication and Likely Pathogenesis
Authors: Rasmussen Angela L. , Diamond Deborah L. , McDermott Jason E. , Gao Xiaoli , Metz Thomas O. , Matzke Melissa M. , Carter Victoria S. , Belisle Sarah E. , Korth Marcus J. , Waters Katrina M. , Smith Richard D. , Katze Michael G. 
Published: September 2011

ABSTRACT
We previously employed systems biology approaches to identify the mitochondrial fatty acid oxidation enzyme dodecenoyl coenzyme A delta isomerase (DCI) as a bottleneck protein controlling host metabolic reprogramming during hepatitis C virus (HCV) infection. Here we present the results of studies confirming the importance of DCI to HCV pathogenesis. Computational models incorporating proteomic data from HCV patient liver biopsy specimens recapitulated our original predictions regarding DCI and link HCV-associated alterations in cellular metabolism and liver disease progression. HCV growth and RNA replication in hepatoma cell lines stably expressing DCI-targeting short hairpin RNA (shRNA) were abrogated, indicating that DCI is required for productive infection. Pharmacologic inhibition of fatty acid oxidation also blocked HCV replication. Production of infectious HCV was restored by overexpression of an shRNA-resistant DCI allele. These findings demonstrate the utility of systems biology approaches to gain novel insight into the biology of HCV infection and identify novel, translationally relevant therapeutic targets.
Persistent Infection Drives the Development of CD8
+
T Cells Specific for Late Lytic Infection Antigens in Lymphocryptovirus-Infected Macaques and Epstein-Barr Virus-Infected Humans
Authors: Orlova Nina , Wang Fred , Fogg Mark H. 
Published: September 2011

ABSTRACT

We examined the CD8
+
T cell repertoire against lytic infection antigens in rhesus macaques persistently infected with the Epstein-Barr virus (EBV)-related lymphocryptovirus (rhLCV). CD8
+
T cells specific for late (L) antigens were detected at rates comparable to those for early antigens and were associated with increasing duration of infection. L antigen-specific CD8
+
T cells were also readily detected in adult, EBV-positive humans. Thus, viral major histocompatibility complex class I (MHCI) immune evasion genes expressed during lytic LCV infection do not prevent L-specific CD8
+
T cell development over time during persistent infection.
Baculovirus Infection Induces a DNA Damage Response That Is Required for Efficient Viral Replication
Authors: Huang Ning , Wu Wenbi , Yang Kai , Passarelli A. Lorena , Rohrmann George F. , Clem Rollie J. 
Published: September 2011

ABSTRACTSeveral mammalian viruses have been shown to induce a cellular DNA damage response during replication, and in some cases, this response is required for optimal virus replication. However, nothing is known about whether a DNA damage response is stimulated by DNA viruses in invertebrates. Cell cycle arrest and apoptosis are two of the downstream effects of the DNA damage response, and both are stimulated by baculovirus infection, suggesting a possible relationship between baculoviruses and the DNA damage response. In the study described in this report, we found that replication of the baculovirusAutographa californicaM nucleopolyhedrovirus (AcMNPV) in the cell line Sf9, derived from the lepidopteran insectSpodoptera frugiperda, stimulated a DNA damage response, as indicated by an increased abundance of theS. frugiperdaP53 protein (SfP53) and phosphorylation of the histone variant protein H2AX. Stimulation of the DNA damage response was dependent on viral DNA replication. Inhibition of the DNA damage response prevented both the increase in SfP53 accumulation and H2AX phosphorylation and also caused a 10- to 100-fold reduction in virus production, along with decreased viral DNA replication and late gene expression. However, silencing ofSfp53expression by RNA interference did not significantly affect AcMNPV replication or induction of apoptosis by a mutant of AcMNPV lacking the antiapoptotic genep35, indicating that these processes are not dependent on SfP53 in Sf9 cells.
010 Quality, performance and performance indicators: use of a standardised template to develop and promote quality and performance in Australasian Emergency Departments: Abstract 010 Figure 1
Authors: Richardson P G 
Published: September 2011

Objectives and BackgroundsWhat counts as quality or performance in the modern emergency department has changed since the inception of the Australasian College for Emergency Medicine (ACEM). Most if not all modern Emergency Physicians already know, that in addition to service provision, they are active and performing a number of other important domains: education and teaching research administration tasks crossing safety, risk management and continuity domains Professional development These other activities have previously not been formally recognised as valid performance measures.MethodsEmergency physicians at the Royal Brisbane and Women's Hospital in Australia embarked on a process to develop a national template to facilitate individual emergency department quality and performance and have this adopted by the ACEM RBWH is the largest adult emergency department in Australasia with 75 000 attendances and staffed by 18 FTE FACEMs. In 2009 a modified Delphi was undertaken following a review of the current literature to identify what could be considered important quality and performance indicators of a highly functioning emergency department. This led to the development of a unifying template the identified all the core areas where emergency physicians are active and are required to show performance in for continuing professional development compliance. These domains can no longer be considered incidental to service provision.ResultsA template was developed with five core domains for emergency departments to show activity in: Quality and Performance Template (Figure 1) .Abstract 010 Figure 1ConclusionsThe template was adopted by the ACEM Quality Sub Committee in September 2010 for further development as a standardised tool and template for promoting quality and performance in Australasian ED's. It will further be developed and enhanced by further research nationally and internationally as to its effectiveness and utility.
019 Nerve blocks: the next hip thing?
Authors: Buxton L 
Published: September 2011

Objectives and BackgroundsFractured neck of femur (NOF) is a common presentation to UK emergency departments (ED) with approximately 75 000 patients admitted annually. Pain control and time to admission are important in this vulnerable group, and yet this is where we repeatedly underperform. Fascia iliac compartment block (FICB) is a well-established and efficacious method of analgesia for fractured hips with fewer side effects than systemic opiates and a longer duration of action. They do, however, mandate 60 min post-block observation in ED to check for signs of local anaesthetic toxicity. Objectives of this study were to evaluate whether delivery of a nerve block prolonged the time patients spent in the department (primary outcome) and whether need for additional analgesia were reduced in those patients receiving nerve blocks (secondary outcomes).MethodsUltrasound-guided FICBs were introduced into practice in Barnsley Hospital ED in July 2010. Training to enable ED nursing staff to deliver landmark-technique blocks commenced in February 2010 as well as a revision of the fractured NOF pathway to incorporate this new practice. An ST5 emergency medicine (EM) trainee and consultant delivered this training with input from the acute pain team. A retrospective review of case notes of all patients with fractured NOF from July 2010 to January 2011 was undertaken to evaluate outcome measures as above. Following introduction of the nurse training, a prospective service evaluation commenced on 01 February 2011 to evaluate outcome measures in patients receiving US guided or landmark technique FICB and standard analgesia. (This data collection is ongoing until 30 June 2011 and results given below are, therefore, preliminary findings).ResultsPatients identified with fractured NOF n=121; of these, 101 received “standard analgesia” (SA) and 21 received a nerve block (NB). Mean “time to admission” for SA=167 min (SD 63.3) and NB= 169 min (SD 48.5) p=0.736* (95% CI −31.2 to 22.1). Mean time to x-ray for SA= 72.54 min (SD 46.4) and NB=49.95 min (SD 24.5) p=0.003* (95% CI 8.15 to 37.03). 71.4% NBs were performed between 08:00 and 18:00 h and 28.6% between 18:00 and 24:00 h. Percentage of patients requiring additional analgesia: SA=20.5%, NB=19%. *Independent t test calculated using SPSS software.ConclusionsResults suggest that patients receiving nerve blocks do not wait longer for admission than those receiving standard analgesia. In a time-target driven world, time to undertake a new intervention is of paramount importance when considering adopting new practice. Nerve blocks were carried out predominantly during the day when senior cover in the department was at a maximum. The mean length of time waiting for an x-ray is lower in the nerve block group suggesting that blocks are done when the department is less busy. As more staff become trained and experienced at nerve block delivery, it is expected that this trend will improve to a “round the clock” service and that block “success” will improve accordingly with reduced additional analgesia requirements.
020 Proformas: how to ensure compliance and is there any point? The Birmingham experience
Authors: Wimalasena Y , Ahee P , Borowska A 
Published: September 2011

Objectives and BackgroundsIn most Emergency Departments (EDs) around the country proformas are in use for the management of patients with specific complaints. Proformas improve documentation, handover and are seen to reduce clinical risk by giving visible guidance to physicians. SWBH encompasses two large EDs seeing over 190 000 patients per year. Head injury, alcohol intoxication and headache proformas were introduced in November 2009, following an analysis of serious untoward incidents (SUIs), to decrease these incidents and improve patient safety. This retrospective analysis was done to evaluate if weekly auditing of proforma use and feedback to clinicians would improve compliance of proforma use and to analyse if use of proformas decreased serious untoward incidents.MethodsEach week (from 31 January 2011 to 09 May 2011) the ED records identified as belonging to patients with head injury, alcohol intoxication or headache were identified by manually combing the triage notes. The use of the proformas for these three conditions was audited. Results were emailed weekly to all clinicians and some were contacted individually. Incidents involving these three conditions were retrospectively looked at for the past 3 years (April 2008 to March 2011).ResultsDuring the study period 780 patients with head injuries, 303 with headache and 127 intoxicated patients were seen. Proforma compliance increased from week 1 to week 15 for head injury (36% to 79%), headache (8% to 64%) and intoxication (38% to 62%). The total number of red and amber incidents involving head injury, headache and intoxication rose from 30 in 2008/2009 to 38 in 2009/2010 and decreased to 23 in 2010/2011.ConclusionsProformas for head injury, alcohol intoxication or headache, were effective at reducing risk and improving patient safety. No patient involved in a serious clinical incident had a proforma used! Our retrospective feedback audit has shown that regular auditing with feedback can improve compliance in proforma use.Abstract 020 Table 1Week vs compliance (%)Head injury proformaAlcohol intoxicationHeadache proformaWeek 136428Week 242743Week 3706342Week 4814429Week 5776458Week 6735761Week 7725050Week 8708567Week 9825025Week 10738071Week 11796264Week 12746658Abstract 020 Figure 1
024 Matrix marking system: a future for debrief and assessment
Authors: Hanson J , Pimblett M , Dickinson M , Jones G , Davis M 
Published: September 2011

Objectives and BackgroundsMedical error accounts for 40 000 deaths per year in the UK, of which 50% are regarded as preventable. There is currently a greater emphasis on patient safety in medical practice; the practice of medicine is dependent on human cognition and although medical error is inevitable, training in both technical and non-technical skills can minimise this. Simulation enables practice in a safe environment and debrief is vital in these skills. The aim of this session is to describe a debrief system which enhances real-time marking through instant video feedback of performance in both technical and non-technical skills.MethodsInitially analogue video systems were used for feedback. Identifying elements for debriefing was time-consuming and unreliable. Using digital recording systems integrated with Studiocode software, we are able to capture elements of a scenario directly onto a hard drive. I Coda software, initially developed to analyse sports performance, is used to code performance against templates developed for specific clinical scenarios. Both technical and non-technical performance can be observed, analysed and coded using an iPad or PDA. This has been developed as a portable system to facilitate observations in theatres, hospital transfers or other clinical environments.ResultsThe Matrix Marking System provides opportunities for instantaneous debriefing after the simulation event in both technical and non-technical skills, based on performance evidence. The facilitator has access to a summary of ratings of performance and an opportunity to replay these for exploration and further analysis.ConclusionsThis brings a new dimension to the debriefing of individual or team performance. The learning conversation (debrief), which develops can be highlighted with instant video feedback to reinforce points for discussion. This system is undergoing validation for debriefing and assessments. We will be looking to report on progress in future meetings.