bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization
of fHbp
,
nhba
(
gna2132
),
nadA
,
porA
, and Sequence Type in Group B Meningococcal Case Isolates Collected in England and Wales during January 2008 and Potential Coverage of an Investigational Group B Meningococcal Vaccine
Authors: Lucidarme Jay , Comanducci Maurizio , Findlow Jamie , Gray Stephen J. , Kaczmarski Edward B. , Guiver Malcolm , Vallely Pamela J. , Oster Philipp , Pizza Mariagrazia , Bambini Stefania , Muzzi Alessandro , Borrow Ray 
Published: April 2010

ABSTRACT

Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (
n
= 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for
fHbp
,
nhba
, and
porA
were identified in all of the isolates, of which 22% were also found to harbor
nadA
alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%.
Comparison of Three Anthrax Toxin Neutralization Assays
Authors: Ngundi Miriam M. , Meade Bruce D. , Lin Tsai-Lien , Tang Wei-Jen , Burns Drusilla L. 
Published: April 2010

ABSTRACT
Different types of anthrax toxin neutralization assays have been utilized to measure the antibody levels elicited by anthrax vaccines in both nonclinical and clinical studies. In the present study, we sought to determine whether three commonly used toxin neutralization assays—J774A.1 cell-, RAW 264.7 cell-, and CHO cell-based assays—yield comparable estimates of neutralization activities for sera obtained after vaccination with anthrax vaccines composed of recombinant protective antigen (rPA). In order to compare the assays, sera were assayed alongside a common reference serum sample and the neutralization titers were expressed relative to the titer for the reference sample in each assay. Analysis of sera from rabbits immunized with multiple doses of the rPA vaccine showed that for later bleeds, the quantitative agreement between the assays was good; however, for early bleeds, some heterogeneity in relative neutralization estimates was observed. Analysis of serum samples from rabbits, nonhuman primates, and humans immunized with the rPA vaccine showed that the relative neutralization estimates obtained in the different assays agreed to various extents, depending on the species of origin of the sera examined. We identified differences in the magnitudes of the Fc receptor-mediated neutralization associated with the J774A.1 cell- and RAW 264.7 cell-based assays, which may account for some of the species dependence of the assays. The differences in the relative neutralization estimates among the assays were relatively small and were always less than 2.5-fold. However, because toxin neutralization assays will likely be used to establish the efficacies of new anthrax vaccines, our findings should be considered when assay outputs are interpreted.
Evaluation of the C.Diff Quik Chek Complete Assay, a New Glutamate Dehydrogenase and A/B Toxin Combination Lateral Flow Assay for Use in Rapid, Simple Diagnosis of
Clostridium difficile
Disease
Authors: Sharp Susan E. , Ruden Lila O. , Pohl Julie C. , Hatcher Patricia A. , Jayne Linda M. , Ivie W. Michael 
Published: April 2010

ABSTRACT

The diagnosis of
Clostridium difficile
infection continues to be a challenge for many clinical microbiology laboratories. A new lateral flow assay, the C.Diff Quik Chek Complete assay, which tests for the presence of both glutamate dehydrogenase (GDH) and
C.
difficile
toxins A and B, was evaluated for its ability to diagnose
C.
difficile
disease. The results of this assay were compared to those of both PCR and toxigenic culture. The results showed that this assay allows 88% of specimens to be accurately screened as either positive (both tests positive) or negative (both tests negative) for the presence of toxigenic
C.
difficile
in less than 30 min and with minimal hands-on time. Use of a random-access PCR for the analysis of specimens with discrepant results (one test positive and the other negative) allows the easy, rapid, and highly sensitive (100%; 95% confidence interval [CI], 89.6 to 100%) and specific (99.6%; 95% CI, 97.3 to 99.9%) diagnosis of
C.
difficile
disease. The use of this algorithm would save institutional costs, curtail unnecessary isolation days, reduce the nosocomial transmission of disease, and increase the quality of care for patients.
Use of Fine-Needle Aspiration for Diagnosis of
Mycobacterium ulcerans
Infection
Authors: Cassisa Viviane , Chauty Annick , Marion Estelle , Ardant Marie Françoise , Eyangoh Sara , Cottin Jane , Aubry Jacques , Koussemou Hugues , Lelièvre Bénédicte , Férec Séverine , Tekaia Fredj , Johnson Christian , Marsollier Laurent 
Published: April 2010

ABSTRACT

Noninvasive methods for the bacteriological diagnosis of early-stage
Mycobacterium ulcerans
infection are not available. It was recently shown that fine-needle aspiration (FNA) could be used for diagnosing
M. ulcerans
infection in ulcerative lesions. We report that FNA is an appropriate sampling method for diagnosing
M. ulcerans
infection in nonulcerative lesions.
Risk Factors and Outcomes Associated with Acquisition of Colistin-Resistant KPC-Producing
Klebsiella pneumoniae
: a Matched Case-Control Study
Authors: Zarkotou Olympia , Pournaras Spyros , Voulgari Evangelia , Chrysos Georgios , Prekates Athanassios , Voutsinas Dionysios , Themeli-Digalaki Katerina , Tsakris Athanassios 
Published: April 2010

ABSTRACT

A matched 1:3 case-control study investigated factors predicting colistin-resistant versus colistin-susceptible KPC-producing
Klebsiella pneumoniae
acquisition and its impact on patient outcomes. Case patients were more often admitted from other institutions (
P =
0.019) and had longer therapy with β-lactam/β-lactamase inhibitors (
P
= 0.002) and higher overall mortality (
P
= 0.05). All 52 study isolates were clonally related, suggesting horizontal dissemination. None of these parameters independently predicted colistin resistance, which probably occurred in a susceptible KPC-KP strain that was subsequently disseminated horizontally.
Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Subgroup J Avian Leukosis Virus
Authors: Zhang Xiaotao , Liao Ming , Jiao Peirong , Luo Kaijian , Zhang Henan , Ren Tao , Zhang Guihong , Xu Chenggang , Xin Chaoan , Cao Weisheng 
Published: April 2010

ABSTRACT
Infection of breeder flocks in China with subgroup J avian leukosis virus (ALV-J) has increased recently. In this study, we have developed a loop-mediated isothermal amplification (LAMP) assay for rapid detection of ALV-J from culture isolates and clinical samples. The ALV-J-specific LAMP assay efficiently amplified the target gene within 45 min at 63°C using only a simple laboratory water bath. To determine the specificity of the LAMP assay, various subgroup ALVs and other related viruses were detected. A ladder pattern on gel electrophoresis was observed for ALV-J isolates but not for other viruses. To evaluate the sensitivities of the LAMP assay and conventional PCR, the NX0101 isolate plasmid DNA was amplified by them. The detection limit of the LAMP assay was 5 target gene copies/reaction, which was up to 20 times higher than that of conventional PCR. To evaluate the application of the LAMP assay for detection of ALV-J in clinical samples, 49 samples suspected of ALV infection from breeder flocks were tested by the LAMP assay and PCR. Moreover, virus isolation from these samples was also performed using cell culture. The positive-sample ratios were 21/49 (43%) by conventional PCR, 26/49 (53%) by the LAMP assay, and 19/46 (41%) by virus isolation. Additionally, a positive LAMP reaction can be visually ascertained by the observation of turbidity or a color change after addition of SYBR green I dye. Consequently, the LAMP assay is a simple, rapid, and sensitive diagnostic method and can potentially be developed for rapid detection of ALV-J infection in the field.
Wide Variation in the Multiplicity of HIV-1 Infection among Injection Drug Users
Authors: Bar Katharine J. , Li Hui , Chamberland Annie , Tremblay Cecile , Routy Jean Pierre , Grayson Truman , Sun Chuanxi , Wang Shuyi , Learn Gerald H. , Morgan Charity J. , Schumacher Joseph E. , Haynes Barton F. , Keele Brandon F. , Hahn Beatrice H. , Shaw George M. 
Published: April 2010

ABSTRACT

Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in heterosexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27;
P
= 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.
Dimeric Architecture of the Hendra Virus Attachment Glycoprotein: Evidence for a Conserved Mode of Assembly
Authors: Bowden Thomas A. , Crispin Max , Harvey David J. , Jones E. Yvonne , Stuart David I. 
Published: April 2010

ABSTRACT

Hendra virus is a negative-sense single-stranded RNA virus within the
Paramyxoviridae
family which, together with Nipah virus, forms the
Henipavirus
genus. Infection with bat-borne Hendra virus leads to a disease with high mortality rates in humans. We determined the crystal structure of the unliganded six-bladed β-propeller domain and compared it to the previously reported structure of Hendra virus attachment glycoprotein (HeV-G) in complex with its cellular receptor, ephrin-B2. As observed for the related unliganded Nipah virus structure, there is plasticity in the Glu579-Pro590 and Lys236-Ala245 ephrin-binding loops prior to receptor engagement. These data reveal that henipaviral attachment glycoproteins undergo common structural transitions upon receptor binding and further define the structural template for antihenipaviral drug design. Our analysis also provides experimental evidence for a dimeric arrangement of HeV-G that exhibits striking similarity to those observed in crystal structures of related paramyxovirus receptor-binding glycoproteins. The biological relevance of this dimer is further supported by the positional analysis of glycosylation sites from across the paramyxoviruses. In HeV-G, the sites lie away from the putative dimer interface and remain accessible to α-mannosidase processing on oligomerization. We therefore propose that the overall mode of dimer assembly is conserved for all paramyxoviruses; however, while the geometry of dimerization is rather closely similar for those viruses that bind flexible glycan receptors, significant (up to 60°) and different reconfigurations of the subunit packing (associated with a significant decrease in the size of the dimer interface) have accompanied the independent switching to high-affinity protein receptor binding in Hendra and measles viruses.
Endocytosis of Murine Norovirus 1 into Murine Macrophages Is Dependent on Dynamin II and Cholesterol
Authors: Perry Jeffrey W. , Wobus Christiane E. 
Published: April 2010

ABSTRACT
Although noroviruses cause the vast majority of nonbacterial gastroenteritis in humans, little is known about their life cycle, including viral entry. Murine norovirus (MNV) is the only norovirus to date that efficiently infects cells in culture. To elucidate the productive route of infection for MNV-1 into murine macrophages, we used a neutral red (NR) infectious center assay and pharmacological inhibitors in combination with dominant-negative (DN) and small interfering RNA (siRNA) constructs to show that clathrin- and caveolin-mediated endocytosis did not play a role in entry. In addition, we showed that phagocytosis or macropinocytosis, flotillin-1, and GRAF1 are not required for the major route of MNV-1 uptake. However, MNV-1 genome release occurred within 1 h, and endocytosis was significantly inhibited by the cholesterol-sequestering drugs nystatin and methyl-β-cyclodextrin, the dynamin-specific inhibitor dynasore, and the dominant-negative dynamin II mutant K44A. Therefore, we conclude that the productive route of MNV-1 entry into murine macrophages is rapid and requires host cholesterol and dynamin II.
A Novel Bicistronic High-Capacity Gutless Adenovirus Vector That Drives Constitutive Expression of Herpes Simplex Virus Type 1 Thymidine Kinase and Tet-Inducible Expression of Flt3L for Glioma Therapeutics
Authors: Puntel Mariana , Muhammad A. K. M. G. , Candolfi Marianela , Salem Alireza , Yagiz Kader , Farrokhi Catherine , Kroeger Kurt M. , Xiong Weidong , Curtin James F. , Liu Chunyan , Bondale Niyati S. , Lerner Jonathan , Pechnick Robert N. , Palmer Donna , Ng Philip , Lowenstein Pedro R. , Castro Maria G. 
Published: April 2010

ABSTRACT

Glioblastoma multiforme (GBM) is a deadly primary brain tumor. Conditional cytotoxic/immune-stimulatory gene therapy (Ad-TK and Ad-Flt3L) elicits tumor regression and immunological memory in rodent GBM models. Since the majority of patients enrolled in clinical trials would exhibit adenovirus immunity, which could curtail transgene expression and therapeutic efficacy, we used high-capacity adenovirus vectors (HC-Ads) as a gene delivery platform. Herein, we describe for the first time a novel bicistronic HC-Ad driving constitutive expression of herpes simplex virus type 1 thymidine kinase (HSV1-TK) and inducible
Tet-
mediated expression of Flt3L within a single-vector platform. We achieved anti-GBM therapeutic efficacy with no overt toxicities using this bicistronic HC-Ad even in the presence of systemic Ad immunity. The bicistronic HC-Ad-TK/TetOn-Flt3L was delivered into intracranial gliomas in rats. Survival, vector biodistribution, neuropathology, systemic toxicity, and neurobehavioral deficits were assessed for up to 1 year posttreatment. Therapeutic efficacy was also assessed in animals preimmunized against Ads. We demonstrate therapeutic efficacy, with vector genomes being restricted to the brain injection site and an absence of overt toxicities. Importantly, antiadenoviral immunity did not inhibit therapeutic efficacy. These data represent the first report of a bicistronic vector platform driving the expression of two therapeutic transgenes, i.e., constitutive HSV1-TK and inducible Flt3L genes. Further, our data demonstrate no promoter interference and optimum gene delivery and expression from within this single-vector platform. Analysis of the efficacy, safety, and toxicity of this bicistronic HC-Ad vector in an animal model of GBM strongly supports further preclinical testing and downstream process development of HC-Ad-TK/TetOn-Flt3L for a future phase I clinical trial for GBM.
Enhancerless Cytomegalovirus Is Capable of Establishing a Low-Level Maintenance Infection in Severely Immunodeficient Host Tissues but Fails in Exponential Growth
Authors: Podlech Jürgen , Pintea Rares , Kropp Kai A. , Fink Annette , Lemmermann Niels A. W. , Erlach Katja C. , Isern Elena , Angulo Ana , Ghazal Peter , Reddehase Matthias J. 
Published: April 2010

ABSTRACT

Major immediate-early transcriptional enhancers are genetic control elements that act, through docking with host transcription factors, as a decisive regulatory unit for efficient initiation of the productive virus cycle. Animal models are required for studying the function of enhancers paradigmatically in host organs. Here, we have sought to quantitatively assess the establishment, maintenance, and level of
in vivo
growth of enhancerless mutants of murine cytomegalovirus in comparison with those of an enhancer-bearing counterpart in models of the immunocompromised or immunologically immature host. Evidence is presented showing that enhancerless viruses are capable of forming restricted foci of infection but fail to grow exponentially.
Virus Cell-to-Cell Transmission
Authors: Mothes Walther , Sherer Nathan M. , Jin Jing , Zhong Peng 
Published: April 2010

ABSTRACTViral infections spread based on the ability of viruses to overcome multiple barriers and move from cell to cell, tissue to tissue, and person to person and even across species. While there are fundamental differences between these types of transmissions, it has emerged that the ability of viruses to utilize and manipulate cell-cell contact contributes to the success of viral infections. Central to the excitement in the field of virus cell-to-cell transmission is the idea that cell-to-cell spread is more than the sum of the processes of virus release and entry. This implies that virus release and entry are efficiently coordinated to sites of cell-cell contact, resulting in a process that is distinct from its individual components. In this review, we will present support for this model, illustrate the ability of viruses to utilize and manipulate cell adhesion molecules, and discuss the mechanism and driving forces of directional spreading. An understanding of viral cell-to-cell spreading will enhance our ability to intervene in the efficient spreading of viral infections.
The ABCs of Rhinoviruses, Wheezing, and Asthma
Authors: Gern James E. 
Published: April 2010

ABSTRACTHuman rhinoviruses (HRVs) were discovered as common cold pathogens over 50 years ago. Recent advances in molecular viral diagnostics have led to an appreciation of their role in more-significant respiratory illnesses, including bronchiolitis in infancy, childhood pneumonia, and acute exacerbations of chronic respiratory diseases such as asthma, chronic obstructive lung disease, and cystic fibrosis. Until a few years ago, only two groups of HRVs (A and B) had been recognized. However, full and partial sequencing of HRVs led to the discovery of a third species of HRV (HRV-C) that has distinct structural and biologic features. Risk factors and pathogenic mechanisms for more-severe HRV infections are being defined, and yet fundamental questions persist about mechanisms relating this common pathogen to allergic diseases and asthma. The close relationship between HRV infections and asthma suggests that antiviral treatments could have a major impact on the morbidity associated with this chronic respiratory disease.
Suppressor of Cytokine Signaling 3 Suppresses Hepatitis C Virus Replication in an mTOR-Dependent Manner
Authors: Shao Run-Xuan , Zhang Leiliang , Peng Lee F. , Sun Eileen , Chung Woo Jin , Jang Jae Yong , Tsai Wei-Lun , Hyppolite Guibenson , Chung Raymond T. 
Published: April 2010

ABSTRACTWe and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection.
Persistence of Viremia and Production of Neutralizing Antibodies Differentially Regulated by PolymorphicAPOBEC3andBAFF-RLoci in Friend Virus-Infected Mice
Authors: Tsuji-Kawahara Sachiyo , Chikaishi Tomomi , Takeda Eri , Kato Maiko , Kinoshita Saori , Kajiwara Eiji , Takamura Shiki , Miyazawa Masaaki 
Published: April 2010

ABSTRACTSeveral host genes control retroviral replication and pathogenesis through the regulation of immune responses to viral antigens. TheRfv3gene influences the persistence of viremia and production of virus-neutralizing antibodies in mice infected with Friend mouse retrovirus complex (FV). This locus has been mapped within a narrow segment of mouse chromosome 15 harboring theAPOBEC3andBAFF-Rloci, both of which show functional polymorphisms among different strains of mice. The exon 5-lacking product of theAPOBEC3allele expressed in FV-resistant C57BL/6 (B6) mice directly restricts viral replication, and mice lacking the B6-derivedAPOBEC3exhibit exaggerated pathology and reduced production of neutralizing antibodies. However, the mechanisms by which the polymorphisms at theAPOBEC3locus affect the production of neutralizing antibodies remain unclear. Here we show that theAPOBEC3genotypes do not directly affect the B-cell repertoire, and mice lacking B6-derivedAPOBEC3still produce FV-neutralizing antibodies in the presence of primed T helper cells. Instead, higher viral loads at a very early stage of FV infection caused by either a lack of the B6-derivedAPOBEC3or a lack of the wild-typeBAFF-Rresulted in slower production of neutralizing antibodies. Indeed, B cells were hyperactivated soon after infection in theAPOBEC3- orBAFF-R-deficient mice. In contrast to mice deficient in the B6-derivedAPOBEC3, which cleared viremia by 4 weeks after FV infection, mice lacking the functionalBAFF-Rallele exhibited sustained viremia, indicating that the polymorphisms at theBAFF-Rlocus may better explain theRfv3-defining phenotype of persistent viremia.