bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Molecular Epidemiology Study ofMycobacterium tuberculosisin Burkina Faso
Authors: Godreuil S. , Torrea G. , Terru D. , Chevenet F. , Diagbouga S. , Supply P. , Van de Perre P. , Carriere C. , Bañuls A. L. 
Published: January 2007

ABSTRACTWe conducted a molecular epidemiology study on 120Mycobacterium tuberculosisisolates from patients presenting pulmonary tuberculosis (TB) in Burkina Faso. Classical antibiogram studies and genetic characterization, using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping, were applied after culture. Molecular analysis of specific signatures showed that all TB cases reported in this study were caused byM. tuberculosisand identified noMycobacterium bovisorMycobacterium africanumisolates. This result is unexpected, asM. africanumstrains were reportedly the etiologic agent in 20% of TB cases 2 decades ago. The comparison of spoligotypes from Burkina Faso with an international spoligotype database (SpolDB4) showed that the majority of isolates belong to major clades ofM. tuberculosis(Haarlem, 9%; Latin American-Mediterranean, 30%; and T, 20%). The predominant group of isolates (30%) corresponds to spoligotype 61, described in Cameroon as the “Cameroon family.” In Burkina Faso, as in Cameroon, this family could be associated with recent transmission of TB, suggesting a recent expansion in West Africa. Our data suggest a low level of primary drug resistance that may be a positive result of the Directly Observed Therapy Shortcourse program. Besides, based on spoligotyping plus MIRU-VNTR, data showed a high number of clusters in our sample, suggesting a high level of recent TB transmission in Burkina Faso. Nevertheless, an important genetic polymorphism was observed in this country, reflecting an endemicity situation where the control of TB would have less impact in the main towns.
Identification of Beijing LineageMycobacterium tuberculosiswith Combined Mycobacterial Interspersed Repetitive Unit Loci 26, 31, and ETR-A
Authors: Chin Pei-Ju , Chiu Chen-Che , Jou Ruwen 
Published: January 2007

ABSTRACTA rapid method for identification of Beijing lineageMycobacterium tuberculosisis still needed in regions of tuberculosis endemicity, especially if genotyping methods are not readily accessible. After analyzing 1,557 clinical isolates, a PCR method with combined mycobacterial interspersed repetitive unit loci 26, 31, and ETR-A for differentiation of Beijing lineage isolates was established, the sensitivity and specificity of which are 94.7% and 98.5%, respectively.
Identification of
Burkholderia pseudomallei
and Related Bacteria by Multiple-Locus Sequence Typing-Derived PCR and Real-Time PCR
Authors: Wattiau Pierre , Van Hessche Mieke , Neubauer Heinrich , Zachariah Reena , Wernery Ulrich , Imberechts Hein 
Published: January 2007

ABSTRACT

Close relatedness and genomic plasticity characterizing the high-threat pathogens
Burkholderia pseudomallei
and
Burkholderia mallei
render the molecular diagnosis of these species hard to guarantee with a maximal confidence level. This article describes fast molecular assays derived from compiled sequences of housekeeping genes determined in more than 1,000 strains. The assays proved to be robust and appropriate for general detection as well as species identification purposes.
Distinct Transcriptional Profiles in Ex Vivo CD4+and CD8+T Cells Are Established Early in Human Immunodeficiency Virus Type 1 Infection and Are Characterized by a Chronic Interferon Response as Well as Extensive Transcriptional Changes in CD8+T Cells
Authors: Hyrcza Martin D. , Kovacs Colin , Loutfy Mona , Halpenny Roberta , Heisler Lawrence , Yang Stuart , Wilkins Olivia , Ostrowski Mario , Der Sandy D. 
Published: January 2007

ABSTRACTChanges in T-cell function are a hallmark of human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms leading to these changes are unclear. We examined the gene expression profiles in ex vivo human CD4+and CD8+T cells from untreated HIV-1-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4+and CD8+T-cell subsets from HIV-1-infected nonprogressors with controlled viremia were indistinguishable from those of individuals not infected with HIV-1. Similarly, no gene clusters could distinguish T cells from individuals with early infection from those seen in chronic progressive HIV-1 infection, whereas differences were observed between uninfected individuals or nonprogressors versus early or chronic progressors. In early and chronic HIV-1 infection, three characteristic gene expression signatures were observed. (i) CD4+and CD8+T cells showed increased expression of interferon-stimulated genes (ISGs). However, some ISGs, including CXCL9, CXCL10, and CXCL11, and the interleukin-15 alpha receptor were not upregulated. (ii) CD4+and CD8+T cells showed a cluster similar to that observed in thymocytes. (iii) More genes were differentially regulated in CD8+T cells than in CD4+T cells, including a cluster of genes downregulated exclusively in CD8+T cells. In conclusion, HIV-1 infection induces a persistent T-cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response and a profile suggesting an active thymic output. These findings highlight the complexity of the host-virus relationship in HIV-1 infection.
Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication
Authors: Ziebuhr John , Schelle Barbara , Karl Nadja , Minskaia Ekaterina , Bayer Sonja , Siddell Stuart G. , Gorbalenya Alexander E. , Thiel Volker 
Published: January 2007

ABSTRACTExpression of the exceptionally large RNA genomes of CoVs involves multiple regulatory mechanisms, including extensive proteolytic processing of the large replicase polyproteins, pp1a and pp1ab, by two types of cysteine proteases: the chymotrypsin-like main protease and papain-like accessory proteases (PLpros). Here, we characterized the proteolytic processing of the human coronavirus 229E (HCoV-229E) amino-proximal pp1a/pp1ab region by two paralogous PLproactivities. Reverse-genetics data revealed that replacement of the PL2proactive-site cysteine was lethal. By contrast, the PL1proactivity proved to be dispensable for HCoV-229E virus replication, although reversion of the PL1proactive-site substitution to the wild-type sequence after several passages in cell culture indicated that there was selection pressure to restore the PL1proactivity. Further experiments showed that both PL1proand PL2prowere able to cleave the nsp1-nsp2 cleavage site, with PL2procleaving the site less efficiently. The PL1pro-negative mutant genotype could be stably maintained in cell culture when the nsp1-nsp2 site was replaced by a short autoproteolytic sequence, suggesting that the major driving force for the observed reversion of the PL1promutation was the requirement for efficient nsp1-nsp2 cleavage. The data suggest that the two HCoV-229E PLproparalogs have overlapping substrate specificities but different functions in viral replication. Within the tightly controlled interplay of the two protease activities, PL2proplays a universal and essential proteolytic role that appears to be assisted by the PL1proparalog at specific sites. Functional and evolutionary implications of the differential amino-terminal polyprotein-processing pathways among the main CoV lineages are discussed.
Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures
Authors: Haim Hillel , Steiner Israel , Panet Amos 
Published: January 2007

ABSTRACT
Characterization of the neutralizing interaction between antibody and virus is hindered by the nonsynchronized progression of infection in cell cultures. Discrete steps of the viral entry sequence cannot be discerned, and thus, the mode of antibody-mediated interference with virus infectivity remains undefined. Here, we magnetically synchronize the motion and cell attachment of human immunodeficiency virus type 1 (HIV-1) to monitor the progression of neutralization, both in solution and following virus attachment to the cell. By simultaneous transfer of all viral particles from reaction solution with antibody to the cell-bound state, the precise rate of neutralization of cell-free virus could be determined for each antibody. HIV-1 neutralization by both monoclonal and polyclonal antibody preparations followed distinct pseudo-first-order kinetics. For all antibodies, cell types, and HIV-1 strains examined, postattachment interference served a major role in the neutralizing effect. To monitor the progression of postattachment interference, we synchronized the entry process at initiation and measured the escape of cell-bound virus from antibody. We found that different antibodies neutralized the virus over different time frames during the entry phase. Virus was observed to progress through a sequence of shifting sensitivities to different antibodies during entry, suggested here to correlate with the exposure time of the target epitope on receptor-activated viral envelope proteins. Thus, by monitoring the progression of HIV-1 entry under synchronized conditions, we identify a new and significant determinant of antibody neutralization capacity, namely, the time frames for neutralization during the course of the viral entry phase.
Inhibition of Human Immunodeficiency Virus Type 1 Infection of Human CD4
+
T Cells by Microbial HSP70 and the Peptide Epitope 407-426
Authors: Babaahmady Kaboutar , Oehlmann Wulf , Singh Mahavir , Lehner Thomas 
Published: January 2007

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) virions contain heat shock proteins (HSP), but these proteins have received limited attention. The objectives of this study were to establish if the microbial 70-kDa HSP exerts an inhibitory effect on the HIV-1 infection of human CD4
+
T cells, to identify an inhibitory peptide epitope within the sequence of HSP70, and to evaluate the kinetic features of any inhibitory activity. The results of these studies suggest that microbial HSP70 exerts dose-dependent inhibition on CCR5 (R5) strains of clades B, C, and D of HIV-1 infecting human CD4
+
T cells. The site of the HIV-1-inhibitory function was identified within the C-terminal peptide binding domain of HSP70, and the function is expressed by the peptide epitope comprising amino acids 407 to 426. The mechanism of inhibition of HIV-1 infectivity by HSP70 is blocking of the CCR5 coreceptors directly and indirectly by inducing CC chemokines and APOBEC3G. The inhibitory effect of HSP70, its C-terminal fragment, or peptide 407-426 may make HSP70 useful as a microbicidal agent. A potentiating noncognate inhibition of HIV-1 infectivity by combined treatment with HSP70 and monoclonal or polyclonal antibody to CCR5 was demonstrated. This novel strategy may be utilized in therapeutic immunization against HIV-1 infection.
Subdominant CD8+T-Cell Responses Are Involved in Durable Control of AIDS Virus Replication
Authors: Friedrich Thomas C. , Valentine Laura E. , Yant Levi J. , Rakasz Eva G. , Piaskowski Shari M. , Furlott Jessica R. , Weisgrau Kimberly L. , Burwitz Benjamin , May Gemma E. , León Enrique J. , Soma Taeko , Napoe Gnankang , Capuano Saverio V. , Wilson Nancy A. , Watkins David I. 
Published: January 2007

ABSTRACT“Elite controllers” are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals’ CD8+cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+T cells expanded up to 2,500-fold above predepletion levels. This wave of CD8+T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+T cells targeting a small number of epitopes, along with broad CD4+T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8+T-cell populations play a key role in maintaining this control.
Rat Cytomegalovirus Gene Expression in Cardiac Allograft Recipients Is Tissue Specific and Does Not Parallel the Profiles Detected In Vitro
Authors: Streblow Daniel N. , van Cleef Koen W. R. , Kreklywich Craig N. , Meyer Christine , Smith Patricia , Defilippis Victor , Grey Finn , Früh Klaus , Searles Robert , Bruggeman Cathrien , Vink Cornelis , Nelson Jay A. , Orloff Susan L. 
Published: January 2007

ABSTRACT
Rat cytomegalovirus (RCMV) is a β-herpesvirus with a 230-kbp genome containing over 167 open reading frames (ORFs). RCMV gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early, and late). However, the extent of viral-gene expression in vivo and its relationship to the in vitro expression are unknown. In this study, we used RCMV-specific DNA microarrays to investigate the viral transcriptional profiles in cultured, RCMV-infected endothelial cells, fibroblasts, and aortic smooth muscle cells and to compare these profiles to those found in tissues from RCMV-infected rat heart transplant recipients. In cultured cells, RCMV expresses approximately 95% of the known viral ORFs with few differences between cell types. By contrast, in vivo viral-gene expression in tissues from rat heart allograft recipients is highly restricted. In the tissues studied, a total of 80 viral genes expressing levels twice above background (5,000 to 10,000 copies per μg total RNA) were detected. In each tissue type, there were a number of genes expressed exclusively in that tissue. Although viral mRNA and genomic DNA levels were lower in the spleen than in submandibular glands, the number of individual viral genes expressed was higher in the spleen (60 versus 41). This finding suggests that the number of viral genes expressed is specific to a given tissue and is not dependent upon the viral load or viral mRNA levels. Our results demonstrate that the profiles, as well as the amplitude, of viral-gene expression are tissue specific and are dramatically different from those in infected cultured cells, indicating that RCMV gene expression in vitro does not reflect viral-gene expression in vivo.
Sensing Infection by Adenovirus: Toll-Like Receptor-Independent Viral DNA Recognition Signals Activation of the Interferon Regulatory Factor 3 Master Regulator
Authors: Nociari Marcelo , Ocheretina Oksana , Schoggins John W. , Falck-Pedersen Erik 
Published: January 2007

ABSTRACTInfection with adenovirus vectors (AdV) results in rapid activation of innate immunity, which serves the dual purpose of stimulating inflammatory antiviral host defenses and the adaptive immune system. Viral recognition by macrophages, dendritic cells, and other cell types requires an ability to sense the presence of a foreign molecular pattern by “pattern recognition receptors.” The nature of the adenoviral sensor, the target ligand of the sensor, and the downstream antiviral signaling response triggered by virus infection have not been defined for this nonenveloped double-stranded DNA (dsDNA) virus. We have identified four critical links involved in AdV recognition by murine antigen-presenting cells (APC) and primary lung fibroblasts: (i) viral recognition occurs chiefly via a Toll-like receptor (TLR)-independent nucleic acid-sensing mechanism recognizing the viral dsDNA genome, (ii) the intact viral particle and capsid proteins are required for efficient intracellular delivery of the viral genome, (iii) delivery of the viral genome triggers interferon regulatory factor 3 (IRF3) phosphorylation, and (iv) IRF3 activation is the required dominant antiviral signaling pathway used by APC, whereas the “primary” involvement of NF-κB, mitogen-activated protein kinase, or Akt pathways is less prominent. In this study we provide the first direct evidence that infection by a dsDNA virus stimulates an IRF3-mediated interferon and proinflammatory response through a TLR-independent DNA-sensing mechanism.
Influence of Coagulation Factor Zymogens on the Infectivity of Adenoviruses Pseudotyped with Fibers from Subgroup D
Authors: Parker Alan L. , McVey John H. , Doctor Jessica H. , Lopez-Franco Oscar , Waddington Simon N. , Havenga Menzo J. E. , Nicklin Stuart A. , Baker Andrew H. 
Published: January 2007

ABSTRACT
Recent evidence supports a role for vitamin K-dependent coagulation zymogens in adenovirus serotype 5 (Ad5, subgroup C) infection of hepatocytes. Here, we assessed the effect of virus-zymogen interaction on cellular transduction using a panel of fiber (f)-pseudotyped viruses derived from subgroup D (f47, f33, f24, f45, f17, f30). Each virus directly bound factor X (FX) as determined by surface plasmon resonance, resulting in enhanced cell surface binding. Infection of HepG2 cells was promoted by FX but not by FVII or FIX, while transduction of CHO cells was blocked in heparan sulfate proteoglycan-deficient cells. This suggests a broad role for FX in adenovirus infectivity.
Circulating Mitochondrial Nucleic Acids Have Prognostic Value for Survival in Patients with Advanced Prostate Cancer
Authors: Mehra Niven , Penning Maarten , Maas Jolanda , van Daal Nancy , Giles Rachel H. , Voest Emile E. 
Published: January 2007

Abstract
Purpose: Advanced prostate cancer represents a heterogeneous disease entity with differences in clinical behavior, response to therapy, and survival. We assessed whether we could distinguish poor from good prognosis patients at presentation in our clinic by means of quantifying circulating cell-free mitochondrial and genomic nucleic acids in plasma.
Experimental Design: We collected plasma from 75 prostate cancer patients and from 14 subjects with benign disease. Nucleic acids were isolated, and mitochondrial DNA (mtDNA; 16S rRNA), mitochondrial RNA (mtRNA; cytochrome c oxidase subunit 1), and genomic DNA (U1A DNA) transcripts were quantified by real-time amplification. An association between cell-free nucleic acids and metastasis, prostate-specific antigen doubling time, and hemoglobin levels was determined. Multivariate Cox proportional hazard and survival estimation studies were done.
Results: We show that elevated mtDNA and mtRNA levels are present in plasma of prostate cancer patients with a poor 2-year survival (P = 0.02 and 0.003, respectively). Cancer patients with high plasma mitochondrial nucleic acids, using a calculated optimal cutoff point, show a decreased survival compared with patients with low levels (35% versus 73% cumulative survival for mtDNA and 21% versus 73% for mtRNA). Multivariate analysis indicates that mtRNA is an independent predictor of 2-year survival.
Conclusions: Quantification of plasma mitochondrial nucleic acids may be used to recognize patients with a poor prognosis. In advanced prostate cancer patients, mtRNA seemed the strongest predictor of overall survival and an independent prognostic factor for cancer-related death. Amplification of mitochondrial nucleic acids shows increased sensitivity and specificity over genomic DNA as diagnostic and prognostic marker in prostate cancer patients.
Decreased NKG2D Expression on CD8+ T Cell Is Involved in Immune Evasion in Patients with Gastric Cancer
Authors: Osaki Tomohiro , Saito Hiroaki , Yoshikawa Toshiaki , Matsumoto Sachiko , Tatebe Shigeru , Tsujitani Shunichi , Ikeguchi Masahide 
Published: January 2007

Abstract
Purpose: Some studies suggest that the immunoreceptor NKG2D expression on CD8+ T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8+ T lymphocytes and its relationship to immune evasion in gastric cancer patients.
Experimental Design: NKG2D expression on both circulating and tumor-infiltrating CD8+ T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression.
Results: NKG2D expression on circulating CD8+ T cells was down-regulated and significantly correlated with IFN-γ production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8+ T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8+ T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8+ T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies.
Conclusions: Decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer.
The von Hippel-Lindau Tumor Suppressor Protein and Clear Cell Renal Carcinoma
Authors: Kaelin William G. 
Published: January 2007

Abstract
Germ line VHL tumor suppressor gene loss-of-function mutations cause von Hippel-Lindau disease, which is associated with an increased risk of central nervous system hemangioblastomas, clear cell renal carcinomas, and pheochromocytomas. Somatic VHL mutations are also common in sporadic clear cell renal carcinomas. The VHL gene product, pVHL, is part of a ubiquitin ligase complex that targets the α-subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for polyubiquitylation, and hence, proteasomal degradation, when oxygen is available. pVHL-defective clear cell renal carcinomas overproduce a variety of mRNAs that are under the control of HIF, including the mRNAs that encode vascular endothelial growth factor, platelet-derived growth factor B, and transforming growth factor α. In preclinical models, down-regulation of HIF-α, especially HIF-2α, is both necessary and sufficient for renal tumor suppression by pVHL. These observations are probably relevant to the demonstrated clinical activity of vascular endothelial growth factor antagonists in clear cell renal carcinoma and form a foundation for the testing of additional agents that inhibit HIF, or HIF-responsive gene products, in this disease.