bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD46Measles Virus Receptor Polymorphisms Influence Receptor Protein Expression and Primary Measles Vaccine Responses in Naive Australian Children
Authors: Clifford Holly D. , Hayden Catherine M. , Khoo Siew-Kim , Zhang Guicheng , Le Souëf Peter N. , Richmond Peter 
Published: February 2012

ABSTRACTDespite the availability of measles vaccines, infants continue to die from measles. Measles vaccine responses vary between individuals, and poor immunogenicity is likely to preclude protection against measles. CD46 is a ubiquitously expressed specific receptor for vaccine strains of measles virus.CD46polymorphisms have not been functionally investigated but may affect CD46 protein expression, which in turn may mediate primary measles antibody responses in infants. In a cohort of children aged 12 to 14 months from Perth, Australia (n= 137), after their first dose of measles-mumps-rubella (MMR) vaccine,CD46polymorphisms were genotyped, and postvaccination measles IgG and CD46 protein expression before and after measles lysate stimulation of cells were measured. ThreeCD46variants (rs7144, rs11118580, and rs2724384) were significantly associated with measles virus-specific IgG levels (P= 0.008,P= 0.026, andP= 0.018, respectively). There were significant differences betweenCD46rs7144 genotypes and CD46 protein expression on T cells, as well as the downregulation of CD46 and T-cell frequency after measles lysate stimulation. We show thatCD46polymorphisms were associated with primary measles antibody responses in naive infants. We also report the first association of a measles virus receptor polymorphism with functional effects on the receptor, suggesting a possible mechanism through which antibody responses are altered. Elucidating all of the interconnecting genetic factors that alter primary measles vaccine responses may be important for identifying children at risk of poor immunogenicity or vaccine failure and for the future design of vaccine strategies to help these children.
Age-Related Differences in Patterns of Increased Bordetella pertussis Antibodies
Authors: Prince Harry E. , Lieberman Jay M. , Cherry James D. 
Published: February 2012

ABSTRACTDuring the period 2008 to 2010, we identified 11,386 serum samples with increased (positive) levels of antibodies recognizingBordetella pertussisantigens. We sought to characterize the distribution of positive antibody result patterns in relation to patient age. IgG and IgA antibodies recognizing pertussis toxin (PT) and filamentous hemagglutinin (FHA) were quantified using a multianalyte immunodetection assay. Four mutually exclusive positive result patterns were observed: increased FHA antibodies only, increased PT IgA but not IgG, increased PT IgG but not IgA, and increased PT IgG and IgA. In patients <21 years old, the predominant pattern was increased PT IgG but not IgA, whereas in patients ≥21 years old, it was increased FHA antibodies only. The proportion of positive serum samples exhibiting increased PT IgA but not IgG was <20% in all age categories but showed a stepwise rise with age. The proportions of positive serum samples exhibiting increased PT IgG and IgA were similar (26 to 32%) in the age categories spanning 11 to 60 years of age but lower in the <11- and >60-year-old groups. In 3 of 5 age categories, a significant rise in the proportion of positive serum samples exhibiting increased FHA antibodies only occurred in 2010. Patterns of positiveB. pertussisantibody results varied with age. The predominance of increased FHA antibodies only in patients >20 years old suggests that many adults thought to haveB. pertussisinfections actually have other infections that induce FHA-reactive antibodies. Similarly, the 2010 rise in the frequency of increased FHA antibodies only in some age groups suggests an increase in non-B. pertussisinfections.
Clinical Validation of a Point-of-Care Multiplexed
In Vitro
Immunoassay Using Monoclonal Antibodies (the MSD Influenza Test) in Four Hospitals in Vietnam
Authors: van Doorn H. Rogier , van Kinh Nguyen , Tuan Ha Manh , Tuan Tran Anh , Minh Ngo Ngoc Quang , Bryant Juliet E. , Hang Vu thi Ty , Uyen Le thi Tham , Thinh Le Quoc , Anh Tran thi Ngoc , Lan Nguyen Phu Huong , Trung Nguyen Vu , Taylor Walter , Merson Laura , Wertheim Heiman F. L. , Farrar Jeremy , Wolbers Marcel , Chau Nguyen van Vinh , de Jong Menno D. 
Published: February 2012

ABSTRACT
Point-of-care (POC) diagnostic tests for influenza can considerably shorten the time to clinical decision making. An investigational POC test based on a multiplexed immunoassay was developed by Meso Scale Diagnostics, LLC (MSD), with the objective to make a more sensitive rapid test that can also subtype influenza A viruses (1977 H1, H3, and H5). Between February and November 2010, we conducted a prospective multicenter study at four hospitals in Vietnam and compared the performance of this test to that of the WHO/CDC real-time reverse transcriptase PCR (RT-PCR) on nasal and throat swab specimens from patients presenting with influenza-like illness. Five hundred sixty-three adults and children with a median age of 25 months were enrolled. Sensitivity and specificity of the test with combined results from nasal and throat swab samples were 74.0% (131/177) and 99.7% (351/352), respectively, compared to RT-PCR. The POC test was as sensitive for influenza virus B as for influenza virus A (74.4% [64/86] versus 73.6% [67/91]). The positivity rate was associated with lower cycle threshold values (a marker for higher viral loads), sample type (73.6% for nasal swab versus 52.4% for throat swab), and younger age. A total of 210 (18.7%) out of 1,126 MSD tests failed, and for 34 (6%) of patients, both test samples failed (these were excluded from the performance analysis). Subtyping could be assessed only for influenza virus A/H3N2, as 1977 H1N1 was not circulating at the time and no H5N1-infected patients were enrolled, and was successful only in 9/54 patients infected with H3 influenza virus who had a positive POC test result for influenza virus A. This novel POC test provided highly sensitive detection of influenza viruses A and B compared to the reported sensitivities of other rapid tests. However, 18.7% of tests failed for technical reasons and subtyping for H3 was poor. Drawbacks to the technology include the requirement for a dedicated reader instrument and the need for continual updating of subtyping antibodies within the test array.
Epidemiology of Klebsiella oxytoca-Associated Diarrhea Detected by Simmons Citrate Agar Supplemented with Inositol, Tryptophan, and Bile Salts
Authors: Cheng Vincent C. C. , Yam Wing-Cheong , Tsang Lee-Lee , Yau Miranda C. Y. , Siu Gilman K. H. , Wong Sally C. Y. , Chan Jasper F. W. , To Kelvin K. W. , Tse Herman , Hung Ivan F. N. , Tai Josepha W. M. , Ho Pak-Leung , Yuen Kwok-Yung 
Published: February 2012

ABSTRACT

We studied the clinical and epidemiological characteristics of
Klebsiella oxytoca
-associated diarrhea in hospitalized patients in Hong Kong. Between 1 November 2009 and 30 April 2011, all inositol-fermenting colonies found on Simmons citrate agar supplemented with inositol, tryptophan, and bile salts (SCITB agar) used for the culturing of diarrheal stool samples were screened by a spot indole test for
K. oxytoca
. The overall sensitivity of SCITB agar plus the spot indole test (93.3%) for the detection of
K. oxytoca
in stool samples was superior to that of MacConkey agar (63.3%), while the specificities were 100% and 60.4%, respectively. The former achieved a 23-fold reduction in the workload and cost of subsequent standard biochemical identifications. Cytotoxin production and the clonality of
K. oxytoca
were determined by a cell culture cytotoxicity neutralization assay using HEp-2 cells and pulsed-field gel electrophoresis (PFGE), respectively. Of 5,581 stool samples from 3,537 patients,
K. oxytoca
was cultured from 117/5,581 (2.1%) stool samples from 104/3,537 (2.9%) patients. Seventy-six of 104 (73.1%) patients with
K. oxytoca
had no copathogens in their diarrheal stool samples. Twenty-four (31.6%) of 76 patients carried cytotoxin-producing strains, which were significantly associated with antibiotic therapy after hospital admission (50% versus 21.2%;
P
= 0.01). Health care-associated diarrhea was found in 44 (42%) of 104 patients with
K. oxytoca
, but there was no epidemiological linkage suggestive of a nosocomial outbreak, and PFGE showed a diverse pattern. None of the patients with cytotoxin-producing
K. oxytoca
developed antibiotic-associated hemorrhagic colitis, suggesting that
K. oxytoca
can cause a mild disease manifesting as uncomplicated antibiotic-associated diarrhea with winter seasonality.
Development and Evaluation of a PCR Assay for Tracking the Emergence and Dissemination of Haitian Variant
ctxB
in Vibrio cholerae O1 Strains Isolated from Kolkata, India
Authors: Naha Arindam , Pazhani G. P. , Ganguly Mou , Ghosh Santanu , Ramamurthy T. , Nandy Ranjan K. , Nair G. Balakrish , Takeda Yoshifumi , Mukhopadhyay Asish K. 
Published: February 2012

ABSTRACT

A PCR-based assay was developed to discriminate the classical, El Tor, and Haitian types of
ctxB
alleles. Our retrospective study using this newly developed PCR showed that Haitian
ctxB
first appeared in Kolkata during April 2006, and 93.3% of strains isolated during 2011 carried the new allele. Dendrogram analysis showed a pulsed-field gel electrophoresis (PFGE) pattern of the new variant strains isolated recently that was distinct from the PFGE pattern of the strains carrying classical
ctxB
that closely matched the 2006 to 2007 variant strains.
Development of a Transcription-Reverse Transcription Concerted Reaction Method for Specific Detection of Human Enterovirus 71 from Clinical Specimens
Authors: Nakajima Naoto , Kitamori Yuka , Ohnaka Satoru , Mitoma Yasutami , Mizuta Katsumi , Wakita Takaji , Shimizu Hiroyuki , Arita Minetaro 
Published: February 2012

ABSTRACT

A transcription-reverse transcription (RT) concerted reaction (TRCR) method was developed for rapid and specific detection of EV71 from clinical specimens. This method was validated with EV71 strains from all of the known genotypes (genotypes A, B1 to B5, and C1 to C5), with detection limits of 10 to 10
3
copies, and was useful for identification of EV71 from throat swabs of patients with hand, foot, and mouth disease (HFMD).
Detection of Carbapenemase Producers in Enterobacteriaceae by Use of a Novel Screening Medium
Authors: Nordmann Patrice , Girlich Delphine , Poirel Laurent 
Published: February 2012

ABSTRACT

A Drigalski agar-based culture medium containing an ertapenem, cloxacillin, and zinc sulfate (Supercarba medium) was tested for screening carbapenemase-producing members of the family
Enterobacteriaceae
. OXA-48 (
n
= 44), NDM (
n
= 25), VIM or IMP (
n
= 27), and KPC producers (
n
= 18) were detected with a low detection limit. Its overall sensitivity (95.6%) was higher than those of the currently available ChromID ESBL (bioMérieux) and CHROMagar KPC (CHROMagar) screening media. The Supercarba medium provides a significant improvement for detection of the most common types of carbapenemase producers.
Clinical and Microbiologic Characteristics of Invasive Streptococcus pyogenes Infections in North and South India
Authors: Haggar Axana , Nerlich Andreas , Kumar Rajesh , Abraham Vinod J. , Brahmadathan Kootallur N. , Ray Pallab , Dhanda Vanita , Joshua John Melbin Jose , Mehra Narinder , Bergmann Rene , Chhatwal G. Singh , Norrby-Teglund Anna 
Published: February 2012

ABSTRACT

The lack of epidemiologic data on invasive
Streptococcus pyogen
es infections in many developing countries is concerning, as
S. pyogenes
infections are commonly endemic in these areas. Here we present the results of the first prospective surveillance study of invasive
Streptococcus pyogenes
infections in India. Fifty-four patients with invasive
S. pyogenes
infections were prospectively enrolled at two study sites, one in the north and one in the south of India. Sterile-site isolates were collected, and clinical information was documented using a standardized questionnaire. Available acute-phase sera were tested for their ability to inhibit superantigens produced by the patient's own isolate using a cell-based neutralizing assay. The most common clinical presentations were bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis were identified. Characterization of the isolates revealed great heterogeneity, with 32 different
emm
subtypes and 29 different superantigen gene profiles being represented among the 49 sterile-site isolates. Analyses of acute-phase sera showed that only 20% of the cases in the north cohort had superantigen-neutralizing activity in their sera, whereas 50% of the cases from the south site had neutralizing activity. The results demonstrate that there are important differences in both clinical presentation and strain characteristics between invasive
S. pyogenes
infections in India and invasive
S. pyogenes
infections in Western countries. The findings underscore the importance of epidemiologic studies on streptococcal infections in India and have direct implications for current vaccine developments.
Mycobacteriophage Marvin: a New Singleton Phage with an Unusual Genome Organization
Authors: Mageeney Catherine , Pope Welkin H. , Harrison Melinda , Moran Deborah , Cross Trevor , Jacobs-Sera Deborah , Hendrix Roger W. , Dunbar David , Hatfull Graham F. 
Published: February 2012

ABSTRACT

Mycobacteriophages represent a genetically diverse group of viruses that infect mycobacterial hosts. Although more than 80 genomes have been sequenced, these still poorly represent the likely diversity of the broader population of phages that can infect the host,
Mycobacterium smegmatis
mc
2
155. We describe here a newly discovered phage, Marvin, which is a singleton phage, having no previously identified close relatives. The 65,100-bp genome contains 107 predicted protein-coding genes arranged in a noncanonical genomic architecture in which a subset of the minor tail protein genes are displaced about 20 kbp from their typical location, situated among nonstructural genes anticipated to be expressed early in lytic growth. Marvin is not temperate, and stable lysogens cannot be recovered from infections, although the presence of a putative
xis
gene suggests that Marvin could be a relatively recent derivative of a temperate parent. The Marvin genome is replete with novel genes not present in other mycobacteriophage genomes, and although most are of unknown function, the presence of amidoligase and glutamine amidotransferase genes suggests intriguing possibilities for the interactions of Marvin with its mycobacterial hosts.
Emergence of Distinct Brome Mosaic Virus Recombinants Is Determined by the Polarity of the Inoculum RNA
Authors: Kwon Sun-Jung , Rao A. L. N. 
Published: February 2012

ABSTRACT

Despite overwhelming interest in the impact exerted by recombination during evolution of RNA viruses, the relative contribution of the polarity of inoculum templates remains poorly understood. Here, by agroinfiltrating
Nicotiana benthamiana
leaves, we show that brome mosaic virus (BMV) replicase is competent to initiate positive-strand [(+)-strand] synthesis on an ectopically expressed RNA3 negative strand [(−) strand] and faithfully complete the replication cycle. Consequently, we sought to examine the role of RNA polarity in BMV recombination by expressing a series of replication-defective mutants of BMV RNA3 in (+) or (−) polarity. Temporal analysis of progeny sequences revealed that the genetic makeup of the primary recombinant pool is determined by the polarity of the inoculum template. When the polarity of the inoculum template was (+), the recombinant pool that accumulated during early phases of replication was a mixture of nonhomologous recombinants. These are longer than the inoculum template length, and a nascent 3′ untranslated region (UTR) of wild-type (WT) RNA1 or RNA2 was added to the input mutant RNA3 3′ UTR due to end-to-end template switching by BMV replicase during (−)-strand synthesis. In contrast, when the polarity of the inoculum was (−), the progeny contained a pool of native-length homologous recombinants generated by template switching of BMV replicase with a nascent UTR from WT RNA1 or RNA2 during (+)-strand synthesis. Repair of a point mutation caused by polymerase error occurred only when the polarity of the inoculum template was (+). These results contribute to the explanation of the functional role of RNA polarity in recombination mediated by copy choice mechanisms.
Epigenetic Histone Modification of Epstein-Barr Virus BZLF1 Promoter during Latency and Reactivation in Raji Cells
Authors: Murata Takayuki , Kondo Yutaka , Sugimoto Atsuko , Kawashima Daisuke , Saito Shinichi , Isomura Hiroki , Kanda Teru , Tsurumi Tatsuya 
Published: February 2012

ABSTRACT

The Epstein-Barr virus (EBV) predominantly establishes latent infection in B cells, and the reactivation of the virus from latency is dependent on the expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical or biological inducers, such as 12-
O
-tetradecanoylphorbol-13-acetate (TPA), calcium ionophores, or histone deacetylase (HDAC) inhibitors. In some cell lines latently infected with EBV, an HDAC inhibitor alone can induce BZLF1 transcription, while the treatment does not enhance expression in other cell lines, such as B95-8 or Raji cells, suggesting unknown suppressive mechanisms besides histone deacetylation in those cells. Here, we found the epigenetic modification of the BZLF1 promoter in latent Raji cells by histone H3 lysine 27 trimethylation (H3K27me3), H3K9me2/me3, and H4K20me3. Levels of active markers such as histone acetylation and H3K4me3 were low in latent cells but increased upon reactivation. Treatment with 3-deazaneplanocin A (DZNep), an inhibitor of H3K27me3 and H4K20me3, significantly enhanced the BZLF1 transcription in Raji cells when in combination with an HDAC inhibitor, trichostatin A (TSA). The knockdown of Ezh2 or Suv420h1, histone methyltransferases for H3K27me3 or H4K20me3, respectively, further proved the suppression of Zp by the methylations. Taken together, the results indicate that H3K27 methylation and H4K20 methylation are involved, at least partly, in the maintenance of latency, and histone acetylation and H3K4 methylation correlate with the reactivation of the virus in Raji cells.
Vpu Augments the Initial Burst Phase of HIV-1 Propagation and Downregulates BST2 and CD4 in Humanized Mice
Authors: Sato Kei , Misawa Naoko , Fukuhara Mitsuko , Iwami Shingo , An Dong Sung , Ito Mamoru , Koyanagi Yoshio 
Published: February 2012

ABSTRACT

While human cells express potent antiviral proteins as part of the host defense repertoire, viruses have evolved their own arsenal of proteins to antagonize them. BST2 was identified as an inhibitory cellular protein of HIV-1 replication, which tethers virions to the cell surface to prevent their release. On the other hand, the HIV-1 accessory protein, Vpu, has the ability to downregulate and counteract BST2. Vpu also possesses the ability to downmodulate cellular CD4 and SLAMF6 molecules expressed on infected cells. However, the role of Vpu in HIV-1 infection
in vivo
remains unclear. Here, using a human hematopoietic stem cell-transplanted humanized mouse model, we demonstrate that Vpu contributes to the efficient spread of HIV-1
in vivo
during the acute phase of infection. Although Vpu did not affect viral cytopathicity, target cell preference, and the level of viral protein expression, the amount of cell-free virions in
vpu
-deficient HIV-1-infected mice was profoundly lower than that in wild-type HIV-1-infected mice. We provide a novel insight suggesting that Vpu concomitantly downregulates BST2 and CD4, but not SLAMF6, from the surface of infected cells. Furthermore, we show evidence suggesting that BST2 and CD4 impair the production of cell-free infectious virions but do not associate with the efficiency of cell-to-cell HIV-1 transmission. Taken together, our findings suggest that Vpu downmodulates BST2 and CD4 in infected cells and augments the initial burst of HIV-1 replication
in vivo
. This is the first report demonstrating the role of Vpu in HIV-1 infection in an
in vivo
model.
Downregulation of Integrin Receptor-Signaling Genes by Epstein-Barr Virus EBNA 3C via Promoter-Proximal and -Distal Binding Elements
Authors: McClellan Michael J. , Khasnis Sarika , Wood C. David , Palermo Richard D. , Schlick Sandra N. , Kanhere Aditi S. , Jenner Richard G. , West Michelle J. 
Published: February 2012

ABSTRACT

Epstein-Barr virus (EBV) establishes a persistent latent infection in B lymphocytes and is associated with the development of numerous human tumors. Epstein-Barr nuclear antigen 3C (EBNA 3C) is essential for B-cell immortalization, has potent cell cycle deregulation capabilities, and functions as a regulator of both viral- and cellular-gene expression. We performed transcription profiling on EBNA 3C-expressing B cells and identified several chemokines and members of integrin receptor-signaling pathways, including
CCL3
,
CCL4
,
CXCL10
,
CXCL11
,
ITGA4
,
ITGB1
,
ADAM28
, and
ADAMDEC1
, as cellular target genes that could be repressed by the action of EBNA 3C alone. Chemotaxis assays demonstrated that downregulation of
CXCL10
and -
11
by EBNA 3C is sufficient to reduce the migration of cells expressing the CXCL10 and -11 receptor CXCR3. Gene repression by EBNA 3C was accompanied by decreased histone H3 lysine 9/14 acetylation and increased histone H3 lysine 27 trimethylation. In an EBV-positive cell line expressing all latent genes, we identified binding sites for EBNA 3C at
ITGB1
and
ITGA4
and in a distal regulatory region between
ADAMDEC1
and
ADAM28
, providing the first demonstration of EBNA 3C association with cellular-gene control regions. Our data implicate indirect mechanisms in
CXCL10
and
CXCL11
repression by EBNA 3C. In summary, we have unveiled key cellular pathways repressed by EBNA 3C that are likely to contribute to the ability of EBV-immortalized cells to modulate immune responses, adhesion, and B-lymphocyte migration to facilitate persistence in the host.