bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meningococcal Outer Membrane Vesicle Vaccines Derived from Mutant Strains Engineered To Express Factor H Binding Proteins from Antigenic Variant Groups 1 and 2
Authors: Koeberling Oliver , Giuntini Serena , Seubert Anja , Granoff Dan M. 
Published: December 2008

ABSTRACT

Meningococcal outer membrane vesicle (OMV) vaccines, which are treated with detergents to decrease endotoxin activity, are safe and effective in humans. However, the vaccines elicit serum bactericidal antibody responses largely directed against PorA, which is antigenically variable. We previously prepared a native (non-detergent-treated) OMV vaccine from a mutant of group B strain H44/76 in which the
lpxL1
gene was inactivated, which resulted in penta-acylated lipid A with attenuated endotoxin activity. To enhance protection, we overexpressed factor H binding protein (fHbp) from the antigenic variant 1 group. The vaccine elicited broad serum bactericidal antibody responses in mice against strains with fHbp variant 1 (∼70% of group B isolates) but not against strains with variant 2 or 3. In the present study, we constructed a mutant of group B strain NZ98/254 with attenuated endotoxin that expressed both endogenous variant 1 and heterologous fHbp variant 2. A mixture of the two native OMV vaccines from the H44/76 and NZ98/254 mutants stimulated proinflammatory cytokine responses by human peripheral blood mononuclear cells similar to those stimulated by control, detergent-treated OMV vaccines from the wild-type strains. In mice, the mixture of the two native OMV vaccines elicited broad serum bactericidal antibody responses against strains with heterologous PorA and fHbp in the variant 1, 2, or 3 group. By adsorption studies, the principal bactericidal antibody target was determined to be fHbp. Thus, native OMV vaccines from mutants expressing fHbp variants have the potential to be safe for humans and to confer broad protection against meningococcal disease from strains expressing fHbp from each of the antigenic variant groups.
Clostridium glycolicum
Isolated from a Patient with Otogenic Brain Abscesses
Authors: Van Leer C. , Wensing A. M. J. , van Leeuwen J. P. , Zandbergen E. G. J. , Swanink C. M. A. 
Published: December 2008

ABSTRACT

We describe a case of brain abscesses with gas formation following otitis media, for which the patient treated himself by placing clay in his ear. Several microorganisms, including
Clostridium glycolicum
, were cultured from material obtained from the patient. This is the first report of an infection in an immunocompetent patient associated with this microorganism.
Evolution of Central Nervous System Multidrug-Resistant
Mycobacterium tuberculosis
and Late Relapse of Cryptic Prosthetic Hip Joint Tuberculosis: Complications during Treatment of Disseminated Isoniazid-Resistant Tuberculosis in an Immunocompromised Host
Authors: Upton Arlo , Woodhouse Andrew , Vaughan Ross , Newton Sandie , Ellis-Pegler Rod 
Published: December 2008

ABSTRACT
We report a case of disseminated isoniazid-resistant tuberculosis in an immunocompromised patient with evolution of rifampin (rifampicin) resistance in the central nervous system. This was cured with intraventricular and oral treatment but was followed by a late relapse of the original infection in a prosthetic hip joint. We provide drug levels in cerebrospinal fluid and serum.
Gordonia araii
Infection Associated with an Orthopedic Device and Review of the Literature on Medical Device-Associated
Gordonia
Infections
Authors: Jannat-Khah Deanna P. , Halsey Eric S. , Lasker Brent A. , Steigerwalt Arnold G. , Hinrikson Hans P. , Brown June M. 
Published: December 2008

ABSTRACT

Gordonia
infections in humans are rare and usually affect immunocompromised patients. We present the first case of
Gordonia araii
infection associated with a medical device in an immunocompetent patient. Sequencing was required for conclusive identification. We compared our case to the 16
Gordonia
species-associated medical device infections reported to date.
Unreliable Extended-Spectrum β-Lactamase Detection in the Presence of Plasmid-Mediated AmpC in
Escherichia coli
Clinical Isolates
Authors: Robberts F. J. L. , Kohner P. C. , Patel R. 
Published: December 2008

ABSTRACT

The emergence of extended-spectrum β-lactamase (ESBL) and plasmid-mediated AmpC (pAmpC) enzymes in
Escherichia coli
raises concern regarding accurate laboratory detection and interpretation of susceptibility testing results. Twenty-six cefpodoxime ESBL screen-positive, cefoxitin-resistant
E. coli
clinical isolates were subjected to clavulanate ESBL confirmatory testing employing disk augmentation, Etest, and the BD Phoenix NMC/ID-132 panel. Phenotypic pAmpC production was assessed by boronic acid disk augmentation. ESBL and pAmpC genes were detected by gene amplification and sequencing. ESBL genes (SHV and/or CTX-M-type genes) were detected in only 7/26 ESBL screen-positive isolates. Of 23 aminophenylboronic acid screen-positive isolates, pAmpC genes were detected in 20 (CMY-2 or FOX-5 genes). High incidences of false-positive ESBL confirmatory results were observed for both clavulanate disk augmentation (9/19) and BD Phoenix (5/19). All were associated with the presence of pAmpC genes with or without TEM-1. Etest performed poorly, as the majority of interpretations were nondeterminable. In addition, false-negative ESBL confirmatory results were observed in isolates possessing concomitant ESBL and pAmpC genes for Etest (four of five), BD Phoenix (three of five), and disk augmentation (one of five). The results indicate poor performance of currently employed ESBL confirmatory methods in the setting of concomitant pAmpC. Some isolates with pAmpC and ESBL genes fell within the susceptible category to extended-spectrum cephalosporins, raising concern over currently employed breakpoints.
Value of Serial Quantification of Fungal DNA by a Real-Time PCR-Based Technique for Early Diagnosis of Invasive Aspergillosis in Patients with Febrile Neutropenia
Authors: Cuenca-Estrella Manuel , Meije Yolanda , Diaz-Pedroche Carmen , Gomez-Lopez Alicia , Buitrago Maria J. , Bernal-Martinez Leticia , Grande Carlos , Juan Rafael San , Lizasoain Manuel , Rodriguez-Tudela Juan L. , Aguado Jose M. 
Published: December 2008

ABSTRACTA study was designed to assess the reliability of the serial detection ofAspergillussp. DNA to diagnose invasive aspergillosis (IA) in patients with febrile neutropenia. Two blood and two serum samples were taken weekly from 83 patients. A total of 2,244 samples were analyzed by real-time quantitative PCR. Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive results as the diagnostic criterion, PCR detected 11 cases, with 4 false positives, giving sensitivity, specificity, positive, and negative predictive values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM) testing, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%. This diagnostic strategy presented, according to CART analysis, a receiver-operator curve with an area under the curve of 0.97 (95% confidence interval, 0.895 to 1.032;P< 0.01), with a relative risk of IA 6.92 times higher than the control population and with predictive success of 95.2%. As regards early diagnosis, the serial detection ofAspergillusDNA took on average 21 days less than HRCT and 68 days less than GM. The serial detection ofAspergillusDNA using real-time quantitative PCR has great diagnostic applicability, which increases when combined with GM quantification.
Molecular Epidemiology of Norovirus Gastroenteritis Investigated Using Samples Collected from Children in Tunisia during a Four-Year Period: Detection of the Norovirus Variant GGII.4 Hunter as Early as January 2003
Authors: Sdiri-Loulizi Khira , Ambert-Balay Katia , Gharbi-Khelifi Hakima , Sakly Nabil , Hassine Mouna , Chouchane Slaheddine , Guediche Mohamed Neji , Pothier Pierre , Aouni Mahjoub 
Published: December 2008

ABSTRACTHuman noroviruses (NoVs) cause epidemic and endemic acute gastroenteritis in children and adults. To study the prevalence and genetic diversity of NoV in children in Tunisia, a total of 788 fecal samples were collected during a 4-year period in the region of Monastir, from children 12 years of age or younger, hospitalized or presenting in dispensaries with symptoms of acute gastroenteritis. NoV was detected by reverse transcription-PCR and confirmed by sequence analysis. This is the first report that describes the molecular epidemiology of NoV in Tunisian children: NoVs were characterized as the causative agent in 128 (16.2%) of the samples. Fourteen samples contained a mixture of two NoVs, and 33 samples were coinfected with additional enteric viruses. Eight distinct NoV genotypes were detected (GGI.2, GGI.4, GGII.1, GGII.4, GGII.8, GGII.14, GGIIb/GGII.2, and GGIIb/GGII.3). GGII.4 was the most prevalent genotype, accounting for 83 (64.8%) cases. Interestingly the GGII.4 variant Hunter, described as spreading all over the world in 2004, was found in Tunisia as early as January 2003. The delay of 1 year between the isolation in Tunisia and the worldwide emergence is somewhat surprising, considering the importance of the contacts between North Africa and Europe particularly. Nevertheless, this illustrates the idea that sporadic gastroenteritis cases may be a reservoir for emerging epidemic NoV strains.
Inhibition of a Large Double-Stranded DNA Virus by MxA Protein
Authors: Netherton Christopher L. , Simpson Jennifer , Haller Otto , Wileman Thomas E. , Takamatsu Haru-Hisa , Monaghan Paul , Taylor Geraldine 
Published: December 2008

ABSTRACT
Increasing evidence points to the importance of the interferon (IFN) response in determining the host range and virulence of African swine fever virus (ASFV). Infection with attenuated strains of ASFV leads to the upregulation of genes controlled by IFN pathways, including myxovirus resistance (Mx) genes that are potent effectors of the antiviral state. Mx gene products are known to inhibit the replication of many negative-sense single-stranded RNA viruses, as well as double-stranded RNA viruses, positive-sense single-stranded RNA viruses, and the reverse-transcribing DNA virus hepatitis B virus. Here, we provide data that extend the known range of viruses inhibited by Mx to include the large double-stranded DNA viruses. Stably transfected Vero cells expressing human MxA protein did not support ASFV plaque formation, and virus replication in these cells was reduced 100-fold compared with that in control cells. In contrast, ASFV replication in cells expressing MxB protein or a mutant MxA protein was similar to that in control Vero cells. There was a drastic reduction in ASFV late protein synthesis in MxA-expressing cells, correlating with the results of previous work on the effect of IFN on viral replication. Strikingly, the inhibition of ASFV replication was linked to the recruitment of MxA protein to perinuclear viral assembly sites, where the protein surrounded the virus factories. Interactions between ASFV and MxA were similar to those seen between MxA and different RNA viruses, suggesting a common inhibitory mechanism.
Sharing of Endogenous Lentiviral Gene Fragments among Leporid Lineages Separated for More than 12 Million Years
Authors: van der Loo W. , Abrantes J. , Esteves P. J. 
Published: December 2008

ABSTRACT

Lentiviruses are causal agents of severe pathologies of a variety of mammals, including cattle and humans (e.g., AIDS and different types of lymphoma). While endogenous forms of lentivirus do not occur in these species, A. Katzourakis and coworkers (A. Katzourakis, M. Tristem, O. G. Pybus, and R. J. Gifford, Proc. Natl. Acad. Sci. USA 104:6261-6265, 2007) recently reported the presence in the genome of the European rabbit (
Oryctolagus cuniculus
) of multiple sequences defining a lentiviral subgroup elegantly referred to as RELIK (
r
abbit
e
ndogenous
l
ent
i
virus type
K
). Sequence comparisons indicated that the RELIK ancestor may have integrated into the rabbit lineage more than 7 million years ago. We have substantiated this by producing sequence data certifying the sharing of RELIK sequences among leporid lineages that diverged some 12 million years ago.
Severe Acute Respiratory Syndrome Coronavirus Triggers Apoptosis via Protein Kinase R but Is Resistant to Its Antiviral Activity
Authors: Krähling Verena , Stein David A. , Spiegel Martin , Weber Friedemann , Mühlberger Elke 
Published: December 2008

ABSTRACTIn this study, infection of 293/ACE2 cells with severe acute respiratory syndrome coronavirus (SARS-CoV) activated several apoptosis-associated events, namely, cleavage of caspase-3, caspase-8, and poly(ADP-ribose) polymerase 1 (PARP), and chromatin condensation and the phosphorylation and hence inactivation of the eukaryotic translation initiation factor 2α (eIF2α). In addition, two of the three cellular eIF2α kinases known to be virus induced, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), were activated by SARS-CoV. The third kinase, general control nonderepressible-2 kinase (GCN2), was not activated, but late in infection the level of GCN2 protein was significantly reduced. Reverse transcription-PCR analyses revealed that the reduction of GCN2 protein was not due to decreased transcription or stability of GCN2 mRNA. The specific reduction of PKR protein expression by antisense peptide-conjugated phosphorodiamidate morpholino oligomers strongly reduced cleavage of PARP in infected cells. Surprisingly, the knockdown of PKR neither enhanced SARS-CoV replication nor abrogated SARS-CoV-induced eIF2α phosphorylation. Pretreatment of cells with beta interferon prior to SARS-CoV infection led to a significant decrease in PERK activation, eIF2α phosphorylation, and SARS-CoV replication. The various effects of beta interferon treatment were found to function independently on the expression of PKR. Our results show that SARS-CoV infection activates PKR and PERK, leading to sustained eIF2α phosphorylation. However, virus replication was not impaired by these events, suggesting that SARS-CoV possesses a mechanism to overcome the inhibitory effects of phosphorylated eIF2α on viral mRNA translation. Furthermore, our data suggest that viral activation of PKR can lead to apoptosis via a pathway that is independent of eIF2α phosphorylation.
Efficient Replication of Human Immunodeficiency Virus Type 1 in Resting CD4+T Lymphocytes Is Induced by Coculture with Autologous Dendritic Cells in the Absence of Foreign Antigens
Authors: Barat Corinne , Gilbert Caroline , Tremblay Michel J. 
Published: December 2008

ABSTRACTDendritic cells (DC) are considered to be important contributors to human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. As the first target cells in mucosal tissues, they can be become productively infected and can also capture virions and transfer them efficiently to CD4+T cells located within lymphoid tissues. Resting CD4+T cells appear to be another major target of HIV-1 in vivo, yet several blocks restrict replication in such cells. We report here that physical contact between virus-infected quiescent CD4+T cells and uninfected autologous immature DC in the absence of any foreign antigen relieves these restrictions, allowing a highly productive HIV-1 replication.
The Chromodomain of Tf1 Integrase Promotes Binding to cDNA and Mediates Target Site Selection
Authors: Chatterjee Atreyi Ghatak , Leem Young Eun , Kelly Felice D. , Levin Henry L. 
Published: December 2008

ABSTRACT

The long terminal repeat (LTR) retrotransposon Tf1 of
Schizosaccharomyces pombe
integrates specifically into the promoters of pol II-transcribed genes. Its integrase (IN) contains a C-terminal chromodomain related to the chromodomains that bind to the N-terminal tail of histone H3. Although we have been unable to detect an interaction between histone tails and the chromodomain of Tf1 IN, it is possible that the chromodomain plays a role in directing IN to its target sites. To test this idea, we generated transposons with single amino acid substitutions in highly conserved residues of the chromodomain and created a chromodomain-deleted mutant. The mutations, V1290A, Y1292A, W1305A, and CHDΔ, substantially reduced transposition activity in vivo. Blotting assays showed that there was little or no reduction in the levels of IN or cDNA. By measuring the homologous recombination between cDNA and the plasmid copy of Tf1, we found that two of the mutations did not reduce the import of cDNA into the nucleus, while another caused a 33% reduction. Chromatin immunoprecipitation assays revealed that CHDΔ caused an approximately threefold reduction in the binding of IN to the downstream LTR of the cDNA. These data indicate that the chromodomain contributed directly to integration. We therefore tested whether the chromodomain contributed to selecting insertion sites. Results of a target plasmid assay showed that the deletion of the chromodomain resulted in a drastic reduction in the preference for pol II promoters. Collectively, these data indicate that the chromodomain promotes binding of cDNA and plays a key role in efficient targeting.
Orthopoxviruses Require a Functional Ubiquitin-Proteasome System for Productive Replication
Authors: Teale Alastair , Campbell Stephanie , Van Buuren Nick , Magee Wendy C. , Watmough Kelly , Couturier Brianne , Shipclark Robyn , Barry Michele 
Published: December 2008

ABSTRACTCellular homeostasis depends on an intricate balance of protein expression and degradation. The ubiquitin-proteasome pathway plays a crucial role in specifically targeting proteins tagged with ubiquitin for destruction. This degradation can be effectively blocked by both chemically synthesized and natural proteasome inhibitors. Poxviruses encode a number of proteins that exploit the ubiquitin-proteasome system, including virally encoded ubiquitin molecules and ubiquitin ligases, as well as BTB/kelch proteins and F-box proteins, which interact with cellular ubiquitin ligases. Here we show that poxvirus infection was dramatically affected by a range of proteasome inhibitors, including MG132, MG115, lactacystin, and bortezomib (Velcade). Confocal microscopy demonstrated that infected cells treated with MG132 or bortezomib lacked viral replication factories within the cytoplasm. This was accompanied by the absence of late gene expression and DNA replication; however, early gene expression occurred unabated. Proteasomal inhibition with MG132 or bortezomib also had dramatic effects on viral titers, severely blocking viral replication and propagation. The effects of MG132 on poxvirus infection were reversible upon washout, resulting in the production of late genes and viral replication factories. Significantly, the addition of an ubiquitin-activating enzyme (E1) inhibitor had a similar affect on late and early protein expression. Together, our data suggests that a functional ubiquitin-proteasome system is required during poxvirus infection.
Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability
Authors: Wang Xiaoyu , Naidu Samisubbu R. , Sverdrup Francis , Androphy Elliot J. 
Published: December 2008

ABSTRACT
The papillomavirus E2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. From a yeast two-hybrid screen, we identified the cellular protein Tax1BP1 as a novel binding partner of human papillomavirus type 18 (HPV18) E2. Tax1BP1 also interacts with the HPV16 and bovine papillomavirus type 1 (BPV1) E2 proteins, with the C-terminal region of Tax1BP1 interacting with the N-terminal transactivation domain of BPV1 E2. Tax1BP1 complexes with p300 and acts synergistically as a coactivator with p300 to enhance E2-dependent transcription. Using chromatin immunoprecipitation assays, we show that Tax1BP1 and E2 localize to the long control region on the BPV1 genome. Tax1BP1 was recently reported to bind ubiquitin and to function as an essential component of an A20 ubiquitin-editing complex. We demonstrate that Tax1BP1 plays a role in the regulation of the steady-state level of E2 by preventing its proteasomal degradation. These studies provide new insights into the regulation of E2 functions.
Arsenic Trioxide Inhibits Hepatitis C Virus RNA Replication through Modulation of the Glutathione Redox System and Oxidative Stress
Authors: Kuroki Misao , Ariumi Yasuo , Ikeda Masanori , Dansako Hiromichi , Wakita Takaji , Kato Nobuyuki 
Published: December 2008

ABSTRACTArsenic trioxide (ATO), a therapeutic reagent used for the treatment of acute promyelocytic leukemia, has recently been reported to increase human immunodeficiency virus type 1 infectivity. However, in this study, we have demonstrated that replication of genome-length hepatitis C virus (HCV) RNA (O strain of genotype 1b) was notably inhibited by ATO at submicromolar concentrations without cell toxicity. RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were also inhibited by ATO after the HCV infection. To clarify the mechanism of the anti-HCV activity of ATO, we examined whether or not PML is associated with this anti-HCV activity, since PML is known to be a target of ATO. Interestingly, we observed the cytoplasmic translocation of PML after treatment with ATO. However, ATO still inhibited the HCV RNA replication even in the PML knockdown cells, suggesting that PML is dispensable for the anti-HCV activity of ATO. In contrast, we found thatN-acetyl-cysteine, an antioxidant and glutathione precursor, completely and partially eliminated the anti-HCV activity of ATO after 24 h and 72 h of treatment, respectively. In this context, it is worth noting that we found an elevation of intracellular superoxide anion radical, but not hydrogen peroxide, and the depletion of intracellular glutathione in the ATO-treated cells. Taken together, these findings suggest that ATO inhibits the HCV RNA replication through modulation of the glutathione redox system and oxidative stress.
Regulation of APOBEC3 Proteins by a Novel YXXL Motif in Human Immunodeficiency Virus Type 1 Vif and Simian Immunodeficiency Virus SIVagm Vif
Authors: Pery Erez , Rajendran Kottampatty S. , Brazier Andrew Jay , Gabuzda Dana 
Published: December 2008

ABSTRACT

The APOBEC3 cytidine deaminases are potent antiviral factors that restrict the replication of human immunodeficiency virus type 1 (HIV-1). In HIV-1-infected CD4
+
T cells, the viral accessory protein Vif binds to APOBEC3G (A3G), APOBEC3F (A3F), and APOBEC3C (A3C) and targets these proteins for polyubiquitination by forming an E3 ubiquitin ligase with cullin 5. Previous studies identified regions of HIV-1 Vif,
40
YRHHY
44
and
12
QVDRMR
17
, which are important for interaction with A3G and A3F, respectively, and showed that Vif residues 54 to 71 are sufficient for A3G binding. Here, we identify
69
YXXL
72
as a novel conserved motif in HIV-1 Vif that mediates binding to human A3G and its subsequent degradation. Studies on other APOBEC3 proteins revealed that Tyr69 and Leu72 are important for the degradation of A3F and A3C as well. Similar to A3F, A3C regulation is also mediated by Vif residues
12
QVDRMR
17
. Simian immunodeficiency virus (SIV) Vif was shown to bind and degrade African green monkey A3G (agmA3G) and, unexpectedly, human A3C. The YXXL motif of SIVagm Vif was important for the inactivation of agmA3G and human A3C. Unlike HIV-1 Vif, however, SIVagm Vif does not require Tyr40 and His43 for agmA3G degradation. Tyr69 in the YXXL motif was critical for binding of recombinant glutathione
S
-transferase-Vif(1-94) to A3G in vitro. These results suggest that the YXXL motif in Vif is a potential target for small-molecule inhibitors to block Vif interaction with A3G, A3F, and A3C, and thereby protect cells against HIV-1 infection.