bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusarium falciforme Vertebral Abscess and Osteomyelitis: Case Report and Molecular Classification
Authors: Edupuganti Srilatha , Rouphael Nadine , Mehta Aneesh , Eaton Molly , Heller John G. , Bressler Adam , Brandt Mary , O'Donnell Kerry 
Published: March 2011

ABSTRACT

Fusarium
is a ubiquitous mold that can cause superficial infections such as keratitis and onychomycosis in immunocompetent humans; however, infections in immunocompromised hosts can be fatal. We report an unusual case of epidural abscess and vertebral osteomyelitis in a patient with an autoimmune disorder who was on long-term glucocorticoids. Multilocus DNA sequence-based typing revealed that the infection was caused by a novel three-locus haplotype of
Fusarium falciforme
designated FSSC 3+4qqq.
Spread of Pseudomonas fluorescens Due to Contaminated Drinking Water in a Bone Marrow Transplant Unit
Authors: Wong Vanessa , Levi Katrina , Baddal Buket , Turton Jane , Boswell Tim C. 
Published: March 2011

ABSTRACT

Pseudomonas
infections are an important cause of morbidity and mortality in immunocompromised patients. We present here data for the spread of
Pseudomonas fluorescens
caused by a contaminated drinking water dispenser in a bone marrow transplant unit. Over a 1-month period we observed a sharp increase in the isolation of
P. fluorescens
from weekly pharyngeal surveillance swabs. Environmental samples were taken from a variety of water sources throughout the unit. These samples were cultured on cetrimide agar medium, and isolates were epidemiologically characterized by antibiotic susceptibility patterns and molecular typing methods. Nine patients became colonized with
P. fluorescens
, and six out of the nine developed febrile neutropenia.
P. fluorescens
was cultured after the filtration of 100 ml of drinking water from one of two stand-alone chiller units supplying cooled bottled water to the bone marrow transplant unit. All other environmental samples were negative. There were no further cases of
P. fluorescens
colonization after the contaminated dispenser was removed. Molecular typing showed that all
P. fluorescens
isolates were identical by both random amplification of polymorphic DNA PCR and pulsed-field gel electrophoresis. We recommend that such bottled water supplies not be used in high-risk areas or be subject to regular microbiological monitoring.
Strain-Tailored Double-Disk Synergy Test Detects Extended-Spectrum Oxacillinases in Pseudomonas aeruginosa
Authors: Hocquet Didier , Dehecq Barbara , Bertrand Xavier , Plésiat Patrick 
Published: March 2011

ABSTRACT

The prevalence of class D extended-spectrum oxacillinases (ES-OXAs) in ceftazidime-resistant strains of
Pseudomonas aeruginosa
is often underestimated by double-disk synergy tests (DDST) using clavulanate. A DDST with a customized distance between a disk of ceftazidime or cefepime and inhibitors (clavulanate and imipenem) detected 14 out of 15 different ES-OXAs.
Emerging Microsporidian Infections in Russian HIV-Infected Patients
Authors: Sokolova Olga I. , Demyanov Anton V. , Bowers Lisa C. , Didier Elizabeth S. , Yakovlev Alexei V. , Skarlato Sergei O. , Sokolova Yuliya Y. 
Published: March 2011

ABSTRACTMicrosporidia were identified in stool specimens by histochemistry and PCR of 30 (18.9%) of 159 HIV-infected patients presenting to the S. P. Botkin Memorial Clinical Hospital of Infectious Diseases, St. Petersburg, Russia. The higher prevalence ofEncephalitozoon intestinalis, in 21 (12.8%) patients, than ofEnterocytozoon bieneusi, in 2 patients (1.2%), was unexpected.Encephalitozoon cuniculiwas detected in three patients: one with strain I and two with strain II.Encephalitozoon hellemwas detected in one patient, and two patients were identified as being infected byMicrosporidiumspecies. One patient was infected with bothE. intestinalisandE. cuniculi. In two patients, the microsporidian species were not identifiable. No statistically significant differences in gender, age, and stage of AIDS were observed between the microsporidian-positive and -negative HIV-infected patients. HIV-infected patients diagnosed with microsporidian infection, however, were significantly more likely to exhibit ≤100 CD4+T cells/μl blood (20/30 patients [67%]; odds ratio [OR], 3.150; 95% confidence interval [CI95], 1.280 to 7.750;P= 0.0116) and weight loss of >10% of the baseline (19/30 patients [63%]; odds ratio, 2.995; CI95, 1.100 to 8.158;P= 0.0352) than HIV-infected patients not diagnosed with microsporidian infection. In summary, this is the first report describing the diagnosis of microsporidian infection of HIV-infected patients in Russia and the first detection ofE. cuniculistrain II in a human.
Baculovirus VP80 Protein and the F-Actin Cytoskeleton Interact and Connect the Viral Replication Factory with the Nuclear Periphery
Authors: Marek Martin , Merten Otto-Wilhelm , Galibert Lionel , Vlak Just M. , van Oers Monique M. 
Published: March 2011

ABSTRACT

Recently, we showed that the
Autographa californica
multicapsid nucleopolyhedrovirus (AcMNPV) VP80 protein is essential for the formation of both virion types, budded virus (BV) and occlusion-derived virus (ODV). Deletion of the
vp80
gene did not affect assembly of nucleocapsids. However, these nucleocapsids were not able to migrate from the virogenic stroma to the nuclear periphery. In the current paper, we constructed a baculovirus recombinant with enhanced-green fluorescent protein (EGFP)-tagged VP80, allowing visualization of the VP80 distribution pattern during infection. In baculovirus-infected cells, the EGFP-VP80 protein is entirely localized in nuclei, adjacent to the virus-triggered F-actin scaffold that forms a highly organized three-dimensional network connecting the virogenic stroma physically with the nuclear envelope. Interaction between VP80 and host actin was confirmed by coimmunoprecipitation. We further showed that VP80 is associated with the nucleocapsid fraction of both BVs and ODVs, typically at one end of the nucleocapsids. In addition, the presence of sequence motifs with homology to invertebrate paramyosin proteins strongly supports a role for VP80 in the polar transport of nucleocapsids to the periphery of the nucleus on their way to the plasma membrane to form BVs and for assembly in the nuclear periphery to form ODVs for embedding in viral occlusion bodies.
Identification of a Golgi Complex-Targeting Signal in the Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Envelope Protein
Authors: Cohen Jennifer R. , Lin Lisa D. , Machamer Carolyn E. 
Published: March 2011

ABSTRACT
The 2003 global outbreak of progressive respiratory failure was caused by a newly emerged virus, severe acute respiratory syndrome coronavirus (SARS-CoV). In contrast to many well-studied enveloped viruses that assemble and bud at the plasma membrane, coronaviruses assemble by budding into the lumen of the endoplasmic reticulum-Golgi intermediate compartment and are released from the cell by exocytosis. For this to occur, the viral envelope proteins must be efficiently targeted to the Golgi region of the secretory pathway. Although the envelope protein (E) makes up only a small percentage of the viral envelope, it plays an important, as-yet-undefined role in virus production. To dissect the targeting of the SARS-CoV E protein to the Golgi region, we exogenously expressed the protein and various mutants from cDNA and determined their localization using immunofluorescence microscopy and biochemical assays. We show that the cytoplasmic tail of the SARS-CoV E protein is sufficient to redirect a plasma membrane protein to the Golgi region. Through site-directed mutagenesis, we demonstrate that a predicted beta-hairpin structural motif in the tail is sufficient for Golgi complex localization of a reporter protein. This motif is conserved in E proteins of beta and gamma coronaviruses (formerly referred to as group 2 and 3 coronaviruses), where it also functions as a Golgi complex-targeting signal. Dissecting the mechanism of targeting of the SARS-CoV E protein will lead to a better understanding of its role in the assembly and release of virions.
The Checkpoints of Viral Gene Expression in Productive and Latent Infection: the Role of the HDAC/CoREST/LSD1/REST Repressor Complex
Authors: Roizman Bernard 
Published: March 2011

ABSTRACT
At the portal of entry into the body, herpes simplex viruses (HSV) vigorously multiply and spread until curtailed by the adaptive immune response. At the same time, HSV invades nerve ending-abutting infected cells and is transported in a retrograde manner to the neuronal nucleus, where it establishes a latent (silent) infection. At intervals, as a consequence of physical or metabolic stress, the virus is activated and transported in an anterograde manner to the body surface. The progression of infection is regulated at four checkpoints. In cell culture or at the portal of entry into the body, HSV uses components of the HDAC1- or HDAC2/CoREST/LSD1/REST repressor complex to activate α genes (checkpoint 1) and then uses an α protein, ICP0, to suppress the same repressor complex from silencing post-α gene expression (checkpoint 2). In neurons destined to harbor latent virus (checkpoint 3), HSV hijacks the same repressor complex to silence itself as a first step in the establishment of the latent state. Suppression of histone deacetylases (HDACs) plays a key role in the reactivation from latency (checkpoint 4). HSV has evolved a strategy of using the same host repressor complex to meet its diverse lifestyle needs.
Interactions of Human Complement with Virus Particles Containing the Nipah Virus Glycoproteins
Authors: Johnson John B. , Aguilar Hector C. , Lee Benhur , Parks Griffith D. 
Published: March 2011

ABSTRACTComplement is an innate immune response system that most animal viruses encounter during natural infections. We have tested the role of human complement in the neutralization of virus particles harboring the Nipah virus (NiV) glycoproteins. A luciferase-expressing vesicular stomatitis virus (VSV) pseudotype that contained the NiV fusion (F) and attachment (G) glycoproteins (NiVpp) showed dose- and time-dependent activation of human complement through the alternative pathway. In contrast to our findings with other paramyxoviruses, normal human serum (NHS) alone did not neutralize NiVpp infectivityin vitro, and electron microscopy demonstrated no significant deposition of complement component C3 on particles. This lack of NiVpp neutralization by NHS was not due to a global inhibition of complement pathways, since complement was found to significantly enhance neutralization by antibodies specific for the NiV F and G glycoproteins. Complement components C4 and C1q were necessary but not sufficient by themselves for the enhancement of antibody neutralization. Human complement also enhanced NiVpp neutralization by a soluble version of the NiV receptor EphrinB2, and this depended on components in the classical pathway. The ability of complement to enhance neutralization fell into one of two profiles: (i) anti-F monoclonal antibodies showed enhancement only at high and not low antibody concentrations, and (ii) anti-G monoclonal antibodies and EphrinB2 showed enhancement at both high and very low levels of antibody (e.g., 3.1 ng) or EphrinB2 (e.g., 2.5 ng). Together, these data establish the importance of human complement in the neutralization of particles containing the NiV glycoproteins and will help guide the design of more effective therapeutics that harness the potency of complement pathways.
Measles Virus Glycoprotein-Pseudotyped Lentiviral Vector-Mediated Gene Transfer into Quiescent Lymphocytes Requires Binding to both SLAM and CD46 Entry Receptors
Authors: Frecha Cecilia , Lévy Camille , Costa Caroline , Nègre Didier , Amirache Fouzia , Buckland Robin , Russell Steven J. , Cosset François-Loïc , Verhoeyen Els 
Published: March 2011

ABSTRACT

Gene transfer into quiescent T and B cells is of importance for gene therapy and immunotherapy approaches to correct hematopoietic disorders. Previously, we generated lentiviral vectors (LVs) pseudotyped with the Edmonston measles virus (MV) hemagglutinin and fusion glycoproteins (Hgps and Fgps) (H/F-LVs), which, for the first time, allowed efficient transduction of quiescent human B and T cells. These target cells express both MV entry receptors used by the vaccinal Edmonston strain, CD46 and signaling lymphocyte activation molecule (SLAM). Interestingly, LVs pseudotyped with an MV Hgp, blind for the CD46 binding site, were completely inefficient for resting-lymphocyte transduction. Similarly, SLAM-blind H mutants that recognize only CD46 as the entry receptor did not allow stable LV transduction of resting T cells. The CD46-tropic LVs accomplished vector-cell binding, fusion, entry, and reverse transcription at levels similar to those achieved by the H/F-LVs, but efficient proviral integration did not occur. Our results indicate that both CD46 and SLAM binding sites need to be present in
cis
in the Hgp to allow successful stable transduction of quiescent lymphocytes. Moreover, the entry mechanism utilized appears to be crucial: efficient transduction was observed only when CD46 and SLAM were correctly engaged and an entry mechanism that strongly resembles macropinocytosis was triggered. Taken together, our results suggest that although vector entry can occur through the CD46 receptor, SLAM binding and subsequent signaling are also required for efficient LV transduction of quiescent lymphocytes to occur.
Species-Specific Variation in RELA Underlies Differences in NF-κB Activity: a Potential Role in African Swine Fever Pathogenesis
Authors: Palgrave Christopher J. , Gilmour Linzi , Lowden C. Stewart , Lillico Simon G. , Mellencamp Martha A. , Whitelaw C. Bruce A. 
Published: March 2011

ABSTRACT

African swine fever virus (ASFV) is a highly infectious disease of domestic pigs, with virulent isolates causing a rapidly fatal hemorrhagic fever. In contrast, the porcine species endogenous to Africa tolerate infection. The ability of the virus to persist in one host while killing another genetically related host implies that disease severity may be, in part, modulated by host genetic variation. To complement transcription profiling approaches to identify the underlying genetic variation in the host response to ASFV, we have taken a candidate gene approach based on known signaling pathways that interact with the virus-encoded immunomodulatory protein A238L. We report the sequencing of these genes from different pig species and the identification and initial
in vitro
characterization of polymorphic variation in RELA (p65; v-rel reticuloendotheliosis viral oncogene homolog A), the major component of the NF-κB transcription factor. Warthog RELA and domestic pig RELA differ at three amino acids. Transient cell transfection assays indicate that this variation is reflected in reduced NF-κB activity
in vitro
for warthog RELA but not for domestic pig RELA. Induction assays indicate that warthog RELA and domestic pig RELA are elevated essentially to the same extent. Finally, mutational studies indicate that the S531P site conveys the majority of the functional variation between warthog RELA and domestic pig RELA. We propose that the variation in RELA identified between the warthog and domestic pig has the potential to underlie the difference between tolerance and rapid death upon ASFV infection.
A Conserved Amphipathic Helix in the N-Terminal Regulatory Region of the Papillomavirus E1 Helicase Is Required for Efficient Viral DNA Replication
Authors: Morin Geneviève , Fradet-Turcotte Amélie , Di Lello Paola , Bergeron-Labrecque Fanny , Omichinski James G. , Archambault Jacques 
Published: March 2011

ABSTRACT

The papillomavirus E1 helicase, with the help of E2, assembles at the viral origin into a double hexamer that orchestrates replication of the viral genome. The N-terminal region (NTR) of E1 is essential for DNA replication
in vivo
but dispensable
in vitro
, suggesting that it has a regulatory function. By deletion analysis, we identified a conserved region of the E1 NTR needed for efficient replication of viral DNA. This region is predicted to form an amphipathic α-helix (AH) and shows sequence similarity to portions of the p53 and herpes simplex virus (HSV) VP16 transactivation domains known as transactivation domain 2 (TAD2) and VP16C, which fold into α-helices upon binding their target proteins, including the Tfb1/p62 (
Saccharomyces cerevisiae
/human) subunit of general transcription factor TFIIH. By nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), we found that a peptide spanning the E1 AH binds Tfb1 on the same surface as TAD2/VP16C and with a comparable affinity, suggesting that it does bind as an α-helix. Furthermore, the E1 NTRs from several human papillomavirus (HPV) types could activate transcription in yeast, and to a lesser extent in mammalian cells, when fused to a heterologous DNA-binding domain. Mutation of the three conserved hydrophobic residues in the E1 AH, analogous to those in TAD2/VP16C that directly contact their target proteins, decreased transactivation activity and, importantly, also reduced by 50% the ability of E1 to support transient replication of DNA in C33A cells, at a step following assembly of the E1-E2-ori preinitiation complex. These results demonstrate the existence of a conserved TAD2/VP16C-like AH in E1 that is required for efficient replication of viral DNA.
What Does Virus Evolution Tell Us about Virus Origins?
Authors: Holmes Edward C. 
Published: March 2011

ABSTRACTDespite recent advances in our understanding of diverse aspects of virus evolution, particularly on the epidemiological scale, revealing the ultimate origins of viruses has proven to be a more intractable problem. Herein, I review some current ideas on the evolutionary origins of viruses and assess how well these theories accord with what we know about the evolution of contemporary viruses. I note the growing evidence for the theory that viruses arose before the last universal cellular ancestor (LUCA). This ancient origin theory is supported by the presence of capsid architectures that are conserved among diverse RNA and DNA viruses and by the strongly inverse relationship between genome size and mutation rate across all replication systems, such that pre-LUCA genomes were probably both small and highly error prone and hence RNA virus-like. I also highlight the advances that are needed to come to a better understanding of virus origins, most notably the ability to accurately infer deep evolutionary history from the phylogenetic analysis of conserved protein structures.
Inhibition of 2′,5′-Oligoadenylate Synthetase Expression and Function by the Human Cytomegalovirus ORF94 Gene Product
Authors: Tan Joanne C. G. , Avdic Selmir , Cao John Z. , Mocarski Edward S. , White Kirsten L. , Abendroth Allison , Slobedman Barry 
Published: March 2011

ABSTRACTThe human cytomegalovirus (HCMV) ORF94 gene product has been reported to be expressed during both productive and latent phases of infection, although its function is unknown. We report that expression of pORF94 leads to decreased 2′,5′-oligoadenylate synthetase (OAS) expression in transfected cells with and without interferon stimulation. Furthermore, the functional activity of OAS was inhibited by pORF94. Finally, we present evidence of OAS modulation by pORF94 during productive HCMV infection of human fibroblasts. This study provides the first identification of a function for pORF94 and identifies an additional means by which HCMV may limit a critical host cell antiviral response.
Pseudotyping Vesicular Stomatitis Virus with Lymphocytic Choriomeningitis Virus Glycoproteins Enhances Infectivity for Glioma Cells and Minimizes Neurotropism
Authors: Muik Alexander , Kneiske Inna , Werbizki Marina , Wilflingseder Doris , Giroglou Tsanan , Ebert Oliver , Kraft Anna , Dietrich Ursula , Zimmer Gert , Momma Stefan , von Laer Dorothee 
Published: March 2011

ABSTRACT

Vesicular stomatitis virus (VSV)-based oncolytic virotherapy has the potential to significantly improve the prognosis of aggressive malignancies such as brain cancer. However, VSV's inherent neurotoxicity has hindered clinical development so far. Given that this neurotropism is attributed to the glycoprotein VSV-G, VSV was pseudotyped with the nonneurotropic envelope glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP→VSV-GP). Compared to VSV, VSV-GP showed enhanced infectivity for brain cancer cells
in vitro
while sparing primary human and rat neurons
in vitro
and
in vivo
, respectively. In conclusion, VSV-GP has a much wider therapeutic window than VSV and is thus more suitable for clinical applications, especially in the brain.
Characterization of Empty Adenovirus Particles Assembled in the Absence of a Functional Adenovirus IVa2 Protein
Authors: Ostapchuk Philomena , Almond Matthew , Hearing Patrick 
Published: March 2011

ABSTRACT

The molecular mechanism for packaging of the adenovirus (Ad) genome into the capsid is likely similar to that of DNA bacteriophages and herpesviruses—the insertion of viral DNA through a portal structure into a preformed prohead driven by an ATP-hydrolyzing molecular machine. It is speculated that the IVa2 protein of adenovirus is the ATPase providing the power stroke of the packaging machinery. Purified IVa2 binds ATP
in vitro
and, along with a second Ad protein, the L4 22-kilodalton protein (L4-22K), binds specifically to sequences in the Ad genome that are essential for packaging. The efficiency of binding of these proteins
in vitro
was correlated with the efficiency of packaging
in vivo
. By utilizing a virus unable to express IVa2,
pm
8002, it was reported that IVa2 plays a role in assembly of the empty virion. We wanted to address the question of whether the ATP binding, and hence the putative ATPase activity, of IVa2 was required for its role in virus assembly. Our results show that ATPase activity was not required for the assembly of empty virus particles. In addition, we present evidence that particles were assembled in the absence of IVa2 by using two viruses null for IVa2—a deletion mutant virus, ΔIVa2, and the previously described mutant virus,
pm
8002. Empty virus particles produced by these IVa2 mutant viruses did not contain detectable viral DNA. We conclude that the major role of IVa2 is in viral DNA packaging. A characterization of the empty particles obtained from the IVa2 mutant viruses compared to wild-type empty particles is presented.
Rift Valley Fever: Recent Insights into Pathogenesis and Prevention
Authors: Boshra Hani , Lorenzo Gema , Busquets Núria , Brun Alejandro 
Published: March 2011

ABSTRACTRift Valley fever virus (RVFV) is a zoonotic pathogen that primarily affects ruminants but can also be lethal in humans. A negative-stranded RNA virus of the familyBunyaviridae, this pathogen is transmitted mainly via mosquito vectors. RVFV has shown the ability to inflict significant damage to livestock and is also a threat to public health. While outbreaks have traditionally occurred in sub-Saharan Africa, recent outbreaks in the Middle East have raised awareness of the potential of this virus to spread to Europe, Asia, and the Americas. Although the virus was initially characterized almost 80 years ago, the only vaccine approved for widespread veterinary use is an attenuated strain that has been associated with significant pathogenic side effects. However, increased understanding of the molecular biology of the virus over the last few years has led to recent advances in vaccine design and has enabled the development of more-potent prophylactic measures to combat infection. In this review, we discuss several aspects of RVFV, with particular emphasis on the molecular components of the virus and their respective roles in pathogenesis and an overview of current vaccine candidates. Progress in understanding the epidemiology of Rift Valley fever has also enabled prediction of potential outbreaks well in advance, thus providing another tool to combat the physical and economic impact of this disease.