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共156条结果
  • 1.

    【2hr】Minor Variant Detection at Different Template Concentrations in HIV-1 Phenotypic and Genotypic Tropism Testing

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    机译 HIV-1表型和基因型趋向性测试中不同模板浓度下的微小变异检测
    摘要：The clinical trials of maraviroc showed that treatment failure was mostly associated with lack of X4 virus detection at baseline. The detection limit for X4 in tropism assays is ill defined around 10%. In the current study, quantification of X4-tropic minority populations was assessed on artificial mixed samples and 38 clinical isolates. These mixtures were subjected to tropism “clonal genotyping” or “population phenotyping”. The detection of minority variants was dependant on the input of amplifiable copies. At VL > 4 log IU/ml, X4 quantification was deemed reliable. PCR founder effect and clonal resampling might result in misrepresentation of the minority species concentration at VL < 4 log. Fourteen of the clinical isolates contained dual/mixed X4-tropic virus, 5 of which were below 10% of the virus population. Currently, there is no indication what level of X4 would lead to treatment failure. Assays aiming for the detection of minority species should express results in function of VL.
  • 2.

    【2hr】Different Isoforms of HPV-16 E7 Protein are Present in Cytoplasm and Nucleus

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    机译 HPV-16 E7蛋白的不同同工型存在于细胞质和细胞核中
    摘要：The E7 protein of high risk HPV types has been found with different molecular weights, mainly because of phosphorylation, an event that changes protein charge and mobility in SDS-PAGE. Distribution of E7 protein in the cellular compartments has also been subject of debate as some groups report the protein in nucleus and others in cytoplasm. The different subcellular distribution and molecular weights reported for the E7 protein suggest the presence of isoforms. We examined this possibility by using several antibodies that recognize different epitopes on the HPV-16 E7 protein. We showed that E7 is processed in 3 isoforms with different molecular weights and isoelectric points (IEP), and described as E7a1 (17.5 kDa, IEP 4.68), E7a (17 kDa, IEP 6.18) and E7b (16 kDa, IEP 6.96). The immunofluorescense results also showed that E7 is distributed into different compartments (ER, Golgi and nucleus), which suggest the presence of other posttranslational modifications, besides phosphorylation.
  • 3.

    【2hr】HIV–1 Antigens in Neurons of Cocaine-Abusing Patients

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    机译 可卡因滥用患者神经元中的HIV-1抗原
    摘要：Cocaine opens the blood-brain barrier by deregulating transcription of target genes. Here we show that cocaine at blood concentrations in drug abusers disrupts endothelial cell junctions in parallel with signaling by phosphorylation of extracellular signal-regulated kinase, myristoylated alanine-rich C kinase and myosin light chain. Cocaine effects may be important in vivo since the neurons of drug abusing patients with HIV-1 associated dementia displayed gp120, p24 and Nef.
  • 4.

    【2hr】New Genetic Lineage of Tula Hantavirus in Microtus arvalis obscurus in Eastern Kazakhstan

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    机译 哈萨克斯坦东部暗纹田鼠图拉汉坦病毒新遗传谱系
    摘要：Genomic sequences of Tula (TULV) hantavirus were recovered from tissue samples of European common voles Microtus arvalis (subspecies obscurus) captured in Kazakhstan, Central Asia. Phylogenetic analysis of the S genomic segment of Kazakh TULV strains showed that they form distinct, well supported genetic lineage and share a more ancient common ancestor with two Russian lineages of TULV. The deduced sequence of the nucleocapsid (N) protein of Kazakh TULV strains carried specific amino acid signature: T274Q276T281. The Microtus arvalis group includes several sibling species and/or subspecies in Eurasia, indicating recent and ongoing evolutionary radiation. Our data on TULV lineages in Central Asia, the region not studied for hantaviruses earlier, highlight the diversity of both Microtus host and the virus and also their co-evolution.
  • 5.

    【2hr】Formulation of New Algorithmics for miRNAs

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    机译 制定miRNA的新算法
    摘要：microRNAs (miRNAs) are a class of small RNAs, 21-25 nucleotides (nts) long with single-stranded RNA. miRNA targets the sequences of messenger RNA (mRNA) through incomplete base-pairing of the target sequence. The incomplete pairing of miRNA to mRNA triggers either translational repression or epigenetically mediated transcriptional gene silencing (TGS). miRNA and RNA silencing in mammalian cells may participate in natural ecological interactions and miRNA itself should contain the original information that is required to control viral proliferation, according to the hypothesis of RNA waves. While the hypothesis involves so-called resident and genomic miRNA as the genetic information, resident miRNAs may evolve and jump into other RNAs, and then become genomic miRNAs. Thus, the inheritable character may be acquired by both types of miRNAs. It is reasonable to believe that preparations of new algorithmics models for the flow of miRNAs may provide an opportunity to overcome the acquired immunodeficiency syndrome (AIDS) pandemic.
  • 6.

    【2hr】Transcriptome Analysis of ESTs from a Chaetognath Reveals a Deep-Branching Clade of Retrovirus-Like Retrotransposons

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    机译 拟南芥ESTs的转录组分析揭示了逆转录病毒样逆转录转座子的分支。
    摘要：Chaetognaths constitute a small marine phylum exhibiting several characteristic which are highly unusual in animal genomes, including two classes of both rRNA and protein ribosomal genes. As in this phylum presence of retrovirus-like elements has never been documented, analysis of a published expressed sequence tag (EST) collection of the chaetognath Spadella cephaloptera has been made. Twelve sequences representing transcript sections of reverse transcriptase domain of active retrotransposons were isolated from~11,000 ESTs. Five of them are originated from Gypsy retrovirus-like elements, whereas the other are transcripts from a Bel-Pao LTR-retrotransposon, a Penelope-like element and LINE retrotransposons. Moreover, a part of a putative integrase has also been found. Phylogenetic analyses suggest a deep-branching clade of the retrovirus-like elements, which is in agreement with the probably Cambrian origin of the phylum. Moreover, retrotransposons have not been found in telomeric-like transcripts which are probably constituted by both vertebrate and arthropod canonical repeats.
  • 7.

    【2hr】Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells

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    机译 腺病毒E1A与潜在基因HHV8启动子的相互作用：E1A蛋白能够激活MV3报告细胞中的HHV-8 LANAp
    摘要：Human herpesvirus 8 (HHV-8) is associated with Kaposi’s sarcoma, body cavity-based lymphoma, and Castleman’s disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the “spacer” region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined.
  • 8.

    【2hr】Supersensitive Viral Load Assay in Predicting CD4-Guided Treatment Failure

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    机译 预测CD4指导治疗失败的超灵敏病毒载量测定
    摘要：In HIV patients who discontinue highly active antiretroviral therapy (HAART), the degree of HIV RNA suppression at the time of treatment interruption may predict success of re-treatment after the interruption (STI). A case-control substudy of the Staccato trial in Thailand included CD4-guided STI subjects with HIV RNA > 50 copies /ml (virological failure cases, n=11) and HIV RNA < 50 copies/ml (controls, n=22) after 12-24 weeks of HAART re-treatment following a median of 2 STI cycles. Controls were matched for age, gender and pre-ART CD4 count. HIV RNA with 5 copies/ml detection limit was determined on pre-virological failure samples. HIV RNA increased in cases compared to controls with each successive STI cycle (p-trend across time-points 0.004). The last HIV RNA below 50 copies/ml was significantly higher among cases compared to controls (p=.004). Measuring HIV RNA below 50 copies/ml may be useful in predicting virological failure to STI.
  • 9.

    【2hr】Human Papillomavirus DNA and E6/E7 mRNA Status in Relation to Survival of Patients Treated for Cervical Squamous Cell Carcinoma

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    机译 人乳头瘤病毒DNA和E6 / E7 mRNA状态与宫颈鳞状细胞癌患者生存率的关系
    摘要：The prognostic significance of human papillomavirus (HPV) DNA and E6/E7 mRNA, the presence of specific types, and the physical state of HPV DNA, were studied in 202 cervical squamous cell carcinomas. Absence or non-detectable levels of high-risk (types 16, 18, 31, 33, 35, 45, 52 and 58) E6/E7 mRNA, using the real-time nucleic acid sequence based amplification (NASBA) assay, and absence of HPV high-risk/HPV 6, 26, 66, 69, 73 (all methods collectively) were associated with poor overall survival in univariate analysis (P = 0.04 and P = 0.03, respectively) and had independent prognostic value in multivariate analysis (P = 0.01 and P = 0.03, respectively) including FIGO stage and age. Based on the individual results of type-specific PCR and in situ hybridization (ISH), the presence of HPV DNA was not found to be a prognostic factor. Likewise, concerning the presence of specific HPV types and the HPV integration status (determined by ISH), no prognostic significance was found. Mutation analyses of the TP53 gene revealed mutations in 3 of the 6 HPV negative samples (50%).
  • 10.

    【2hr】Initiation of Human Immunodeficiency Virus Type 1 (HIV-1) Transcription is Inhibited by Noncytolytic CD8+ Suppression

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    机译 非溶细胞性CD8 +抑制抑制人类免疫缺陷病毒1型（HIV-1）转录的启动。
    摘要：The replication of human immunodeficiency virus type 1 (HIV-1) can be inhibited by noncytolytic CD8+ T cell mediated suppression, an immune response that specifically targets HIV-1 gene expression. Clinical studies demonstrate that this immune response may play an important role in the host defense against HIV infection. In this study, we examined the distinct steps in viral gene expression for inhibition by noncytolytic CD8+ T cells. A primary HIV-1 infection system of CD4+ enriched peripheral blood mononuclear cells was utilized to examine the HIV-1 life cycle as a relevant ex vivo system. Established CD8+ T cell lines from two HIV+ long-term nonprogressors were used to examine differences at the level of transcriptional initiation and elongation of the HIV genome. This infection system coupled with the results from real-time measurement of newly transcribed RNA transcripts determined that there was a significant decrease (5-8 fold) in short intracellular viral RNA transcripts. These data strongly favor a role for the initiation of virus transcription in noncytolytic CD8+ T cell mediated suppression.
  • 11.

    【2hr】Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy

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    机译 逆转录酶密码子135突变对基于NNRTI的治疗反应的临床意义
    摘要：To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm3 (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy.
  • 12.

    【2hr】Targeted Strategies for Henipavirus Therapeutics

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    机译 肝炎病毒治疗的靶向策略
    摘要：Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.
  • 13.

    【2hr】Heterogeneity of Signal Transducer and Activator of Transcription Binding Sites in the Long-Terminal Repeats of Distinct HIV-1 Subtypes

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    机译 在不同的HIV-1亚型的长期重复中信号转导和转录结合位点激活剂的异质性。
    摘要：HIV-1 can be subdivided into distinct subtypes; the consequences of such a genomic variability remain largely speculative. The long terminal repeats (LTR) control HIV transcription and reflect the major differences of distinct viral subtypes. Three regions in the HIV-1 subtype B LTR are close matches to the Signal Transducer and Activator of Transcription (STAT) consensus sequence. Here, we show heterogeneity in these putative STAT binding sites among HIV-1 LTR subtypes A through G. Transfection of constitutively activated STAT5 lead to transcriptional activation of HIV-1 expression in 293T cells transfected with a reporter assay driven by HIV-1 LTR subtype B. Constitutively activated STAT5 transactivated the LTR of various subtypes in U937 cells with different potency. These findings support and expand the potential relevance of STAT5 activation in HIV infection and may bear relevance for a differential regulation of latency and expression of different subtypes of HIV-1.
  • 14.

    【2hr】NFI is an Essential Positive Transcription Factor for Human Papillomavirus Type 16 Early Gene Expression

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    机译 NFI是人类乳头瘤病毒16型早期基因表达的重要正转录因子。
    摘要：Human papillomavirus type 16 (HPV16) is the primary etiologic agent for greater than 50% of all cervical carcinomas. Expression of the HPV16 E6 and E7 oncoproteins is under control of the upstream regulatory region (URR), which contains a myriad of transcription factor binding sites, including 7 half sites for NFI. These NFI binding sites were used as probes in electrophoretic mobility shift assays (EMSAs), and mutational analysis of individual and multiple NFI binding sites was performed in order to demonstrate the relative importance of particular NFI sites to URR activity. By using 5 NFI half sites as an enhancer, we were able to detect a 4-fold increase in URR activity. Our results define the role and relative contribution of NFI binding sites to the basal activity of the HPV16 promoter, and demonstrate that NFI binding sites can act independently to enhance HPV16 URR activity in immortalized keratinocytes.
  • 15.

    【2hr】Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria

    包量

    机译 通过半胱天冬酶8杀死HIV蛋白酶的分析揭示了半胱天冬酶8和线粒体之间的新型相互作用。
    摘要：Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. Since casp8p41 does not contain the catalytic cysteine at position 360, the mechanism by which casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly causes mitochondrial depolarization and release of cytochrome c with downstream caspase 9 activation. Moreover, death induced by casp8p41 requires the presence of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria. These results illuminate a novel mechanism of cell death induced by a caspase 8 cleavage fragment whereby mitochondrial interaction leads to depolarization and cytochrome c release.
  • 16.

    【2hr】Changing Epidemiology of Rotavirus-Related Hospitalizations in Rio De Janeiro, Brazil, from 2002 to 2006

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    机译 2002年至2006年，巴西里约热内卢与轮状病毒相关住院的流行病学变化
    摘要：A prospective hospital-based sentinel study conducted in Rio de Janeiro identified a shift in the pattern (long to short electropherotype and P(8) to P(4) genotype) of rotavirus strains recovered from children with severe diarrhea a few months after the far-reaching Brazilian rotavirus immunization program was launched, posing new interesting challenges.
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