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  1. Microfluidic assay without blocking for rapid HIV screening and confirmation.

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    Song, Lusheng; Zhang, Yi; Wang, Wenjun; Ma, Liying; Liu, Yong; Hao, Yanlin; Shao, Yiming; Zhang, Wei; Jiang, Xingyu

    2012-08-01

    The essential step for HIV spreading limitation is the screening tests. However, there are multiple disadvantages in current screening assays which need further confirmation test. Herein we developed a rapid HIV assay combining screening and confirmation test by using the microfluidic network assay. Meanwhile, the assay is accelerated by bypassing the step of blocking. We call this method as microfluidic assay without blocking (MAWB). Both the limit of detection and reagent incubation time of MAWB are determined by screening of one model protein pair: ovalbumin and its antibody. The assay time is accelerated about 25% while the limit of detection (LOD) is well kept. Formatting the method in for both HIV screening (testing 8 HIV-related samples) and confirmation (assaying 6 kinds of HIV antibodies of each sample) within 30 min was successful. Fast HIV screening and confirmation of 20 plasma samples were also demonstrated by this method. MAWB improved the assay speed while keeping the LOD of conventional ELISA. Meanwhile, both the accuracy and throughput of MAWB were well improved, which made it an excellent candidate for a quick HIV test for both screening and confirmation. Methods like this one will find wide applications in clinical diagnosis and biochemical analysis based on the interactions between pairs of molecules.

  2. Lectins with Anti-HIV Activity: A Review

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    Ouafae Akkouh

    2015-01-01

    Full Text Available Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin lectin, concanavalin A, Galanthus nivalis (snowdrop agglutinin-related lectins, Musa acuminata (banana lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  3. HIV Blocks Interferon Induction in Human Dendritic Cells and Macrophages by Dysregulation of TBK1

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    Harman, Andrew N.; Nasr, Najla; Feetham, Alexandra; Galoyan, Ani; Alshehri, Abdullateef A.; Rambukwelle, Dharshini; Botting, Rachel A.; Hiener, Bonnie M.; Diefenbach, Eve; Diefenbach, Russell J.; Kim, Min; Mansell, Ashley

    2015-01-01

    ABSTRACT Dendritic cells (DCs) and macrophages are present in the tissues of the anogenital tract, where HIV-1 transmission occurs in almost all cases. These cells are both target cells for HIV-1 and represent the first opportunity for the virus to interfere with innate recognition. Previously we have shown that both cell types fail to produce type I interferons (IFNs) in response to HIV-1 but that, unlike T cells, the virus does not block IFN induction by targeting IFN regulatory factor 3 (IRF3) for cellular degradation. Thus, either HIV-1 inhibits IFN induction by an alternate mechanism or, less likely, these cells fail to sense HIV-1. Here we show that HIV-1 (but not herpes simplex virus 2 [HSV-2] or Sendai virus)-exposed DCs and macrophages fail to induce the expression of all known type I and III IFN genes. These cells do sense the virus, and pattern recognition receptor (PRR)-induced signaling pathways are triggered. The precise stage in the IFN-inducing signaling pathway that HIV-1 targets to block IFN induction was identified; phosphorylation but not K63 polyubiquitination of TANK-binding kinase 1 (TBK1) was completely inhibited. Two HIV-1 accessory proteins, Vpr and Vif, were shown to bind to TBK1, and their individual deletion partly restored IFN-β expression. Thus, the inhibition of TBK1 autophosphorylation by binding of these proteins appears to be the principal mechanism by which HIV-1 blocks type I and III IFN induction in myeloid cells. IMPORTANCE Dendritic cells (DCs) and macrophages are key HIV target cells. Therefore, definition of how HIV impairs innate immune responses to initially establish infection is essential to design preventative interventions, especially by restoring initial interferon production. Here we demonstrate how HIV-1 blocks interferon induction by inhibiting the function of a key kinase in the interferon signaling pathway, TBK1, via two different viral accessory proteins. Other viral proteins have been shown to target the

  4. A novel approach to block HIV-1 coreceptor CXCR4 in non-toxic manner.

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    Liu, Ye; Zhou, Jieqiong; Pan, Ji-An; Mabiala, Prudence; Guo, Deyin

    2014-10-01

    The chemokine receptor CXCR4 is one of the major coreceptors for human immunodeficiency virus type 1 (HIV-1) and considered as an important therapeutic target. Knockdown of CXCR4 by RNA interference has emerged as a promising strategy for combating HIV-1 infection. However, there is a potential drawback to this strategy as undesired side effects may occur due to the loss of natural function of CXCR4. In this study, we developed a novel approach using a single lentiviral vector to express simultaneously CXCR4 dual-shRNAs and an shRNA-resistant CXCR4 mutant possessing the most possible natural functions of CXCR4 and reduced HIV-1 coreceptor activity. Via this approach we achieved the replacement of endogenous CXCR4 by CXCR4 mutant P191A that could compensate the functional loss of endogenous CXCR4 and significant reduction of HIV-1 replication by 59.2 %. Besides, we demonstrated that construction of recombinant lentiviral vector using 2A peptide-based strategy has significant advantages over using additional promoter-based strategy, including increase of lentivirus titer and avoidance of promoter competition. Therefore, the novel approach to block HIV-1 coreceptor CXCR4 without impairing its normal function provides a new strategy for CXCR4-targeted therapeutics for HIV-1 infection and potential universal applications to knock down a cellular protein in non-toxic manner.

  5. Cenicriviroc blocks HIV entry but does not lead to redistribution of HIV into extracellular space like maraviroc

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    Victor Kramer

    2014-11-01

    Full Text Available Introduction: Cenicriviroc (CVC, a once-daily, dual CCR5/CCR2 co-receptor antagonist, has completed Phase 2b development. CVC demonstrated favourable safety and similar efficacy compared with efavirenz (EFV in Study 202 (NCT01338883; an ex vivo sub-analysis evaluated treatment effects on HIV entry, measured by intracellular HIV DNA declines, in subjects with virologic success at Week 24. In addition, in vitro assays determined and compared the extent of any cell-free virion redistribution that CVC or maraviroc (MVC may cause. Methods: Ex vivo: intracellular DNA (frozen PBMCs from 30 subjects with virologic success at Week 24 (10, 13 and 7 subjects on CVC 100 mg, CVC 200 mg and EFV, respectively. Early (strong-stop and late (full-length reverse transcript levels were measured by qPCR. In vitro: PM-1 cells were infected with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of CVC (20 nM, MVC (50 nM or controls. P24 and viral load levels were measured by ELISA and qRT-PCR after 4 hours. Results: Ex vivo analysis showed full-length HIV DNA declines were similar across all groups (CVC 100 mg, CVC 200 mg and EFV at Week 24. Strong-stop HIV DNA declines (a marker of HIV entry at Week 24 were pronounced for both CVC arms (CVC 100 mg, 51% decline; CVC 200 mg, 37% decline compared to no decline for the EFV arm. In vitro experiments revealed that CVC-treated cells had lower levels of supernatant P24 at 4 hours versus baseline (0 hrs: 506 ng/mL; 4 hrs: 192 ng/mL, but P24 levels remained constant for MVC-treated cells after 4 hours (0 hrs: 506 ng/mL; 4 hrs: 520 ng/mL. Viral load levels for CVC-treated cells remained stable after 4 hours (0 hrs: 1.19×1010 copies/mL; 4 hrs: 1.26×1010 copies/mL. MVC-treated cells exhibited a slight increase in viral load after 4 hours (0 hrs: 1.19×1010 copies/mL; 4 hrs: 1.67×1010 copies/mL. Conclusions: Ex vivo analysis confirmed that CVC treatment blocks HIV entry (strong-stop HIV DNA declines

  6. Relief of preintegration inhibition and characterization of additional blocks for HIV replication in primary mouse T cells.

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    Jing-xin Zhang

    Full Text Available Development of a small animal model to study HIV replication and pathogenesis has been hampered by the failure of the virus to replicate in non-primate cells. Most studies aimed at achieving replication in murine cells have been limited to fibroblast cell lines, but generating an appropriate model requires overcoming blocks to viral replication in primary T cells. We have studied HIV-1 replication in CD4(+ T cells from human CD4/CCR5/Cyclin T1 transgenic mice. Expression of hCD4 and hCCR5 in mouse CD4(+ T cells enabled efficient entry of R5 strain HIV-1. In mouse T cells, HIV-1 underwent reverse transcription and nuclear import as efficiently as in human T cells. In contrast, chromosomal integration of HIV-1 proviral DNA was inefficient in activated mouse T cells. This process was greatly enhanced by providing a secondary T cell receptor (TCR signal after HIV-1 infection, especially between 12 to 24 h post infection. This effect was specific for primary mouse T cells. The pathways involved in HIV replication appear to be PKCtheta-, CARMA1-, and WASp-independent. Treatment with Cyclosporin A (CsA further relieved the pre-integration block. However, transcription of HIV-1 RNA was still reduced in mouse CD4(+ T cells despite expression of the hCyclin T1 transgene. Additional post-transcriptional defects were observed at the levels of Gag expression, Gag processing, Gag release and virus infectivity. Together, these post-integration defects resulted in a dramatically reduced yield of infectious virus (300-500 fold after a single cycle of HIV-1 replication. This study implies the existence of host factors, in addition to those already identified, that are critical for HIV-1 replication in mouse cells. This study also highlights the differences between primary T cells and cell lines regarding pre-integration steps in the HIV-1 replication cycle.

  7. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients

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    Isabel Sada-Ovalle

    2015-10-01

    Full Text Available Introduction: T cell immunoglobulin and mucin domain (Tim 3 and programmed death 1 (PD-1 are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviral therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. Materials and methods: HIV+ patients naïve to anti-retroviral therapy (ART were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1 was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. Results: We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions: In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and

  8. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients

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    Sada-Ovalle, Isabel; Ocaña-Guzman, Ranferi; Pérez-Patrigeón, Santiago; Chávez-Galán, Leslie; Sierra-Madero, Juan; Torre-Bouscoulet, Luis; Addo, Marylyn M.

    2015-01-01

    Introduction T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD-1) are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviral therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. Materials and methods HIV+ patients naïve to anti-retroviral therapy (ART) were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. Results We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro

  9. Gp120/CD4 blocking antibodies are frequently elicited in ART-naive chronically HIV-1 infected individuals.

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    Jorge Carrillo

    Full Text Available Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies, can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine.

  10. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

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    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Chen, Han [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Zhou, You [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Nebraska Center for Virology, Lincoln, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Nebraska Center for Virology, Lincoln, NE (United States)

    2014-11-15

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release.

  11. Phenotypic Knockout of HIV-1 Chemokine Coreceptor CXCR4 and CCR5 by Intrakines for Blocking HIV-1 Infection

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    张颖; 张岩; 王平忠; 王九平; 黄长形; 孙永涛; 白雪帆

    2004-01-01

    To investigate the phenotypic knockout of HIV-1 chemokine coreceptor CXCR4 and CCR5 by intrakines and its inhibitory effect on HIV-1 infection. Primary human PBLs were transduced with the recombinant vector pLNCX-R-K-S-K(△NGFR), followed by anti-NGFR/anti-IgG-magnetic bead method selection and FCM detection. The transduced PBLs were infected with DP1 HIV-1 virus thereafter envelope-mediated syncytium formation and p24 detection were carried out to study the blockage of HIV-1 infection by co-inactivation of CCR5 and CXCR4. pLNCX-R-K-S-K (△NGFR)-transduced PBILs were isolated with an anti-NGFR/anti-IgG-magnetic bead method. After isolation, about 70% of the PBLs were positive for the NGFR marker. When the transduced PBLs were infected with DP1 HIV-1 virus, envelop-mediated syncytium formation was almost completely inhibited by pLNCX-R-K-S-K(△NGFR) transfection. Also, p24 antigen was very low in the cultures of pLNCX-R-K-S-K (△NGFR) transduced PBLs. pLNCX-R-K-S-K(△NGFR) transduction inhibited the production of DP1 p24 antigen by 15%, 43% and 19% on days 4, 7 and 10 respectively. The lymphocytes with the phenotypic knockout of CCR5 and CXCR4 could protect primary human PBLs from DP1 HIV-1 virus infection.

  12. HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex

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    Alessandro Cinti

    2016-03-01

    Full Text Available Stress granules (SGs are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E-binding protein 1 (4EBP1. In this work, we show that human immunodeficiency virus type 1 (HIV-1 Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms.

  13. Domain 15 of the serine proteinase inhibitor LEKTI blocks HIV infection in vitro

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    David Palesch

    2013-08-01

    Full Text Available Background: Lympho-epithelial Kazal-type-related inhibitor (LEKTI is a 15-domain serine proteinase inhibitor, parts of which have first been isolated from human blood filtrate. It is encoded by the gene SPINK5. In the past, different groups reported antiviral activities of certain serine proteinase inhibitors, such as mucous proteinase inhibitor and alpha1-proteinase inhibitor. The purpose of this study was to test two representative domains of the proteinase inhibitor LEKTI for anti-HIV activities.Methods: LEKTI domains 6 and 15 were recombinantly produced in E.coli. To test their inhibitory activity against HIV infection, the reporter cell line P4-R5 MAGI carrying an HIV-inducible reporter gene was infected by a CCR5-tropic HIV strain in the presence of different inhibitor concentrations. After three days, infection rates were determined by quantifying ß-galactosidase activities using the Galacto-Light Plus™ ß-Galactosidase Reporter Gene Assay.Results: In contrast to LEKTI domain 6, LEKTI domain 15 suppressed HIV-induced reporter gene activities with an IC50 value of approximately 29 µM.Conclusion: LEKTI domain 15 represents an inhibitor of HIV infection. (Med J Indones. 2013;22:131-5. doi: 10.13181/mji.v22i3.580Keywords: HIV, inhibition, LEKTI, P4-R5 MAGI

  14. HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

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    Tahir Bashir

    Full Text Available Human Immunodeficiency Virus (HIV-1 poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL and CXCR4-tropic HIV-1 strains (IIIB and NL4-3. Surface plasmon resonance (SPR and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV. Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.

  15. Blocking of HIV-1 Infectivity by a Soluble, Secreted Form of the CD4 Antigen

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    Smith, Douglas H.; Byrn, Randal A.; Marsters, Scot A.; Gregory, Timothy; Groopman, Jerome E.; Capon, Daniel J.

    1987-12-01

    The initial event in the infection of human T lymphocytes, macrophages, and other cells by human immunodeficiency virus (HIV-1) is the attachment of the HIV-1 envelope glycoprotein gp120 to its cellular receptor, CD4. As a step toward designing antagonists of this binding event, soluble, secreted forms of CD4 were produced by transfection of mammalian cells with vectors encoding versions of CD4 lacking its transmembrane and cytoplasmic domains. The soluble CD4 so produced binds gp120 with an affinity and specificity comparable to intact CD4 and is capable of neutralizing the infectivity of HIV-1. These studies reveal that the high-affinity CD4-gp120 interaction does not require other cell or viral components and may establish a novel basis for therapeutic intervention in the acquired immune deficiency syndrome (AIDS).

  16. Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex.

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    Madison, Marisa N; Jones, Philip H; Okeoma, Chioma M

    2015-08-01

    Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission.

  17. Study on the effectiveness of blocking of maternal - neonatal transmission for HIV -infected pregnant women%HIV感染孕妇母婴阻断效果研究

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    桂秀芝; 邱慧; 覃婷

    2012-01-01

    目的:评估HIV母婴阻断效果,为预防艾滋病母婴传播工作提供借鉴.方法:在围生期门诊为初次建卡产前检查的孕妇检测抗- HIV,为HIV感染孕妇提供综合性母婴阻断措施,临产前采血检测HIV病毒载量,对婴儿HIV感染状况进行随访,即产后4月内2次为婴儿采血检测HIV - DNA,12、18月龄时再次检测抗- HIV.结果:近4年来该院孕妇HIV感染率为0.28%,经采取综合性母婴阻断措施,孕期进行规范三联抗病毒治疗,82.71%的孕妇临产时病毒载量低于最低检测限,婴儿HIV感染率0.75%,明显低于未治疗者之婴儿(感染率25.00%),差异有统计学意义(P<0.05).结论:为HIV感染孕妇实施综合性母婴阻断措施安全有效,不失为预防艾滋病母婴传播的有利措施.%Objective; To evaluate the effectiveness of blocking of HIV maternal - neonatal transmission, and provide reference for preventing maternal - neonatal transmission of HIV. Methods; HIV antibodies were detected in the pregnant women who registered and received prenatal examination for the first time in perinatal outpatient department, then comprehensive blocking measures of maternal - neonatal transmission of HIV were provided to HIV -infected pregnant women, HIV load was detected in labor, the HIV infection status of infants was followed up: HIV DNA of infants were detected twice within four months after birth, HIV antibodies were detected at 12 and 18 months. Results; In recent four years, the infection rate of HIV in pregnant women from the hospital was 0. 28%. After comprehensive blocking measures of maternal - neonatal transmission of HIV and regular triple antiviral therapy during pregnancy period, the viral load of 82. 7% of the pregnant women in labor was lower than the lowest detection limit; the infection rate of HIV in infants was 0. 75% , which was statistically significantly lower than that in infants without treatment (25.00% ) (P <0. 05 ) . Conclusion; Comprehensive

  18. APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication.

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    Yanxing Han

    2008-07-01

    Full Text Available APOBEC3G (A3G/APOBEC3F (A3F are two members of APOBEC3 cytidine deaminase subfamily. Although they potently inhibit the replication of vif-deficient HIV-1, this mechanism is still poorly understood. Initially, A3G/A3F were thought to catalyze C-to-U transitions on the minus-strand viral cDNAs during reverse transcription to disrupt the viral life cycle. Recently, it was found more likely that A3G/A3F directly interrupts viral reverse transcription or integration. In addition, A3G/A3F are both found in the high-molecular-mass complex in immortalized cell lines, where they interact with a number of different cellular proteins. However, there has been no evidence to prove that these interactions are required for A3G/A3F function. Here, we studied A3G/A3F-restricted HIV-1 replication in six different human T cell lines by infecting them with wild-type or vif-deficient HIV-1. Interestingly, in a CEM-derived cell line CEM-T4, which expresses high levels of A3G/A3F proteins, the vif-deficient virus replicated as equally well as the wild-type virus, suggesting that these endogenous antiretroviral genes lost anti-HIV activities. It was confirmed that these A3G/A3F genes do not contain any mutation and are functionally normal. Consistently, overexpression of exogenous A3G/A3F in CEM-T4 cells still failed to restore their anti-HIV activities. However, this activity could be restored if CEM-T4 cells were fused to 293T cells to form heterokaryons. These results demonstrate that CEM-T4 cells lack a cellular cofactor, which is critical for A3G/A3F anti-HIV activity. We propose that a further study of this novel factor will provide another strategy for a complete understanding of the A3G/A3F antiretroviral mechanism.

  19. The anti-inflammatory activity of curcumin protects the genital mucosal epithelial barrier from disruption and blocks replication of HIV-1 and HSV-2.

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    Victor H Ferreira

    Full Text Available Inflammation is a known mechanism that facilitates HIV acquisition and the spread of infection. In this study, we evaluated whether curcumin, a potent and safe anti-inflammatory compound, could be used to abrogate inflammatory processes that facilitate HIV-1 acquisition in the female genital tract (FGT and contribute to HIV amplification. Primary, human genital epithelial cells (GECs were pretreated with curcumin and exposed to HIV-1 or HIV glycoprotein 120 (gp120, both of which have been shown to disrupt epithelial tight junction proteins, including ZO-1 and occludin. Pre-treatment with curcumin prevented disruption of the mucosal barrier by maintaining ZO-1 and occludin expression and maintained trans-epithelial electric resistance across the genital epithelium. Curcumin pre-treatment also abrogated the gp120-mediated upregulation of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL-6, which mediate barrier disruption, as well as the chemokines IL-8, RANTES and interferon gamma-induced protein-10 (IP-10, which are capable of recruiting HIV target cells to the FGT. GECs treated with curcumin and exposed to the sexually transmitted co-infecting microbes HSV-1, HSV-2 and Neisseria gonorrhoeae were unable to elicit innate inflammatory responses that indirectly induced activation of the HIV promoter and curcumin blocked Toll-like receptor (TLR-mediated induction of HIV replication in chronically infected T-cells. Finally, curcumin treatment resulted in significantly decreased HIV-1 and HSV-2 replication in chronically infected T-cells and primary GECs, respectively. All together, our results suggest that the use of anti-inflammatory compounds such as curcumin may offer a viable alternative for the prevention and/or control of HIV replication in the FGT.

  20. X-Ray Structures of the Hexameric Building Block of the HIV Capsid

    Energy Technology Data Exchange (ETDEWEB)

    Pornillos, Owen; Ganser-Pornillos, Barbie K.; Kelly, Brian N.; Hua, Yuanzi; Whitby, Frank G.; Stout, C. David; Sundquist, Wesley I.; Hill, Christopher P.; Yeager, Mark; (Scripps); (Utah)

    2009-09-11

    The mature capsids of HIV and other retroviruses organize and package the viral genome and its associated enzymes for delivery into host cells. The HIV capsid is a fullerene cone: a variably curved, closed shell composed of approximately 250 hexamers and exactly 12 pentamers of the viral CA protein. We devised methods for isolating soluble, assembly-competent CA hexamers and derived four crystallographically independent models that define the structure of this capsid assembly unit at atomic resolution. A ring of six CA N-terminal domains form an apparently rigid core, surrounded by an outer ring of C-terminal domains. Mobility of the outer ring appears to be an underlying mechanism for generating the variably curved lattice in authentic capsids. Hexamer-stabilizing interfaces are highly hydrated, and this property may be key to the formation of quasi-equivalent interactions within hexamers and pentamers. The structures also clarify the molecular basis for capsid assembly inhibition and should facilitate structure-based drug design strategies.

  1. 基于趋化因子受体CCR5阻断HIV-1感染的方法%Methods for blocking HIV-1 infection based on chemokine receptor 5

    Institute of Scientific and Technical Information of China (English)

    季海艳; 夏海滨

    2013-01-01

    获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)主要是由HIV-1感染人体免疫细胞所造成,而介导HIV-1病毒进入机体细胞的主要辅助受体为趋化因子受体CCR5 [chemokine (C-Cmotif) receptor 5],目前以CCR5为研究靶点阻断HIV-l感染的方法在医学和生物学领域备受关注,主要包括CCR5拮抗剂、RNA干扰(RNA interference,RNAi)、锌指核酸酶(zinc-finger nuclease,ZFN)和转录激活因子样效应物核酸酶(transcription activator-like effectors nuclease,TALEN)技术.趋化因子受体CCR5阻断HIV-1感染方法的相关研究进展有必要进行综述.%Acquired immunodeficiency syndrome is mainly caused by HIV-1 infection of the human immune cell. The entry of HIV-1 into target cells is mediated by a major coreceptor, CCR5. Currently, a lot of interest has been focused on the methods for blocking HIV-1 infection using CCR5 as a target in medical and biological research. These methods include CCR5 antagonists, small interfering RNA, and ZFNs (zinc finger nucleases) and TALENs (transcription activator-like effectors nucleases) techniques. It is necessary to review the progress on the methods for blocking HIV-1 infection based on chemokine receptor 5.

  2. The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Philippe A Gallay

    Full Text Available HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV-1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs, the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro "co-infection" model where HCV and HIV-1 concurrently replicate in their respective main host target cells--human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI, including a novel cyclosporin A (CsA analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the "co-infection" system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI--alisporivir (ALV--at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI-431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections.

  3. Macrophage inducible nitric oxide synthase gene expression is blocked by a benzothiophene derivative with anti-HIV properties.

    Science.gov (United States)

    Carballo, M; Conde, M; Tejedo, J; Gualberto, A; Jimenez, J; Monteseirín, J; Santa María, C; Bedoya, F J; Hunt, S W; Pintado, E; Baldwin, A S; Sobrino, F

    2002-04-01

    Nitric oxide (NO) has been shown to mediate multiple physiological and toxicological functions. The inducible nitric oxide synthase (iNOS) is responsible for the high output generation of NO by macrophages following their stimulation by cytokines or bacterial antigens. The inhibition of TNF alpha-stimulated HIV expression and the anti-inflammatory property of PD144795, a new benzothiophene derivative, have been recently described. We have now analyzed whether some of these properties could be mediated by an effect of PD144795 on NO-dependent inflammatory events. We show that PD144795 suppresses the lipopolysaccharide-elicited production of nitrite (NO(-)(2)) by primary peritoneal mouse macrophages and by a macrophage-derived cell line, RAW 264.7. This effect was dependent on the dose and timing of addition of PD144795 to the cells. Suppression of NO(-)(2) production was associated with a decrease in the amount of iNOS protein, iNOS enzyme activity and mRNA expression. The effect of PD144795 was partially abolished by coincubation of the cells with LPS and IFN gamma. However, the inhibitory effect of PD144795 was not abrogated by the simultaneous addition of LPS and TNF alpha, which indirectly suggests that the effect of PD144795 was not due to the inhibition of TNF alpha synthesis. Additionally, PD144795 did not block NF-kappa B nuclear translocation induced by LPS. Inhibition of iNOS gene expression represents a novel mechanism of PD144795 action that underlines the anti-inflammatory effects of this immunosuppressive drug.

  4. Development of an HIV-1 Microbicide Based on Caulobacter crescentus: Blocking Infection by High-Density Display of Virus Entry Inhibitors.

    Directory of Open Access Journals (Sweden)

    Christina Farr

    Full Text Available The HIV/AIDS pandemic remains an enormous global health concern. Despite effective prevention options, 2.6 million new infections occur annually, with women in developing countries accounting for more than half of these infections. New prevention strategies that can be used by women are urgently needed. Topical microbicides specific for HIV-1 represent a promising prevention strategy. Conceptually, using harmless bacteria to display peptides or proteins capable of blocking entry provides an inexpensive approach to microbicide development. To avoid the potential pitfalls of engineering commensal bacteria, our strategy is to genetically display infection inhibitors on a non-native bacterium and rely on topical application of stabilized bacteria before potential virus exposure. Due to the high density cell-surface display capabilities and the inherent low toxicity of the bacterium, the S-layer mediated protein display capabilities of the non-pathogenic bacterium Caulobacter crescentus has been exploited for this approach. We have demonstrated that C. crescentus displaying MIP1α or CD4 interfered with the virus entry pathway and provided significant protection from HIV-1 pseudovirus representing clade B in a standard single cycle infection assay. Here we have expanded our C. crescentus based microbicide approach with additional and diverse classes of natural and synthetic inhibitors of the HIV-1 entry pathway. All display constructs provided variable but significant protection from HIV-1 infection; some with protection as high as 70%. Further, we describe protection from infection with additional viral clades. These findings indicate the significant potential for engineering C. crescentus to be an effective and readily adaptable HIV-1 microbicide platform.

  5. Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

    Science.gov (United States)

    Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

    2008-05-01

    CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

  6. HIV感染孕妇母婴阻断的16例临床效果分析%Clinical Effect Analysis of 16 Cases of Maternal and Child Blocking of HIV Infection in Pregnant Women

    Institute of Scientific and Technical Information of China (English)

    吴爱萍

    2015-01-01

    目的:分析研讨感染 HIV 病毒的孕妇母婴阻断抗病毒治疗的临床效果。方法选取我院2011~2014年内发现的16例 HIV 阳性孕妇的临床资料,针对 HIV 阳性孕妇采用抗病毒治疗,辅助其他治疗,联合应用拉米夫定及克力芝、齐多夫定,新生儿出生后给予应用齐多夫定糖浆至产后42天,新生儿出生后,1、3、6、12、18月龄进行HIV-RNA 检测。结果出生后的新生儿未发现感染 HIV 病毒,均为正常儿童,成功阻断病毒的侵入。结论采用母婴抗病毒治疗能够有效阻止 HIV 病毒母婴传播。%Objective To study the clinical effect of anti viral therapy for pregnant women with infected HIV virus. Methods The clinical data of 16 cases of HIV positive pregnant women were selected in our hospital from 2011 to 2014, according to Yang HIV positive pregnant women received antiviral treatment, other adjuvant therapies, lamivudine and kriton Shiba, Zidorf, after the birth to the application of Zidovudine Syrup to 42 days postpartum, after birth, 1, 3, 6, 12, 18 months were detected by HIV-RNA. Results After birth were found infected with HIV, were normal children, successfully blocked the invasion of the virus. Conclusion The maternal antiviral therapy can effectively prevent HIV virus transmission.

  7. Maternal HIV occupational exposure in maternal and infant block after thinking and protective analysis%HIV孕产妇母婴阻断中职业暴露后思考及防护分析

    Institute of Scientific and Technical Information of China (English)

    李竹艳

    2013-01-01

    目的:通过分析在医护人员对 HIV 孕产妇母婴阻断中进行护理工作时职业暴露的风险,提出防护措施;方法:回顾性分析2009年1月至2010年1月我院收治的 HIV 孕产妇对其进行母婴阻断,在护理工作过程中对职业暴露的医护人员进行统计,分析防护比率;结果:工作伴随职业暴露的12例医护人员均无发生 HIV 感染;结论:为保证所有在职业暴露的医护人员不发生感染,在做好防护措施的同时,要求医护人员要有强烈的自我保护意识,以保证 HIV 孕产妇母婴阻断的顺利进行。%Objective :Through the analysis in medical personnel to HIV maternal maternal and child care work in blocking the risk of occupational exposure ,and puts forward the protective measures ;Methods :Retrospective analysis in January 2009 to January 2010 were our HIV maternal the ma-ternal and child block ,in the nursing process to occupational exposure medical personnel statistics ,analysis protection ratio ;Results :Working with occupational exposure and 12 cases of medical personnel are not happen HIV infection ;Conclusion:To ensure that all occupational exposure in the medical personnel is not an infection ,for protective measures at the same time ,request medical staff should have strong ego to protect consciousness , to ensure that the maternal HIV mother -to -child blocking smoothly .

  8. Medicinal chemistry of small molecule CCR5 antagonists for blocking HIV-1 entry: a review of structural evolution.

    Science.gov (United States)

    Tian, Ye; Zhang, Dujuan; Zhan, Peng; Liu, Xinyong

    2014-01-01

    CCR5, a member of G protein-coupled receptors superfamily, plays an important role in the HIV-1 entry process. Antagonism of this receptor finally leads to the inhibition of R5 strains of HIV entry into the human cells. The identification of CCR5 antagonists as antiviral agents will provide more option for HAART. Now, more than a decade after the first small molecule CCR5 inhibitor was discovered, great achievements have been made. In this article, we will give a brief introduction of several series of small molecule CCR5 antagonists, focused on their appealing structure evolution, essential SAR information and thereof the enlightenment of strategies on CCR5 inhibitors design.

  9. Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors

    Directory of Open Access Journals (Sweden)

    Simmonds Peter

    2008-01-01

    Full Text Available Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. Results R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542, but with increased resistance to the anti-CD4 monoclonal antibody (mab, Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120. Conclusion Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.

  10. Comparative molecular surface analysis (CoMSA) for virtual combinatorial library screening of styrylquinoline HIV-1 blocking agents.

    Science.gov (United States)

    Niedbala, Halina; Polanski, Jaroslaw; Gieleciak, Rafal; Musiol, Robert; Tabak, Dominik; Podeszwa, Barbara; Bak, Andrzej; Palka, Anna; Mouscadet, Jean-Francois; Gasteiger, Johann; Le Bret, Marc

    2006-12-01

    We used comparative molecular surface analysis to design molecules for the synthesis as part of the search for new HIV-1 integrase inhibitors. We analyzed the virtual combinatorial library (VCL) constituted from various moieties of styrylquinoline and styrylquinazoline inhibitors. Since imines can be applied in a strategy of dynamic combinatorial chemistry (DCC), we also tested similar compounds in which the -C=N- or -N=C- linker connected the heteroaromatic and aromatic moieties. We then used principal component analysis (PCA) or self-organizing maps (SOM), namely, the Kohonen neural networks to obtain a clustering plot analyzing the diversity of the VCL formed. Previously synthesized compounds of known activity, used as molecular probes, were projected onto this plot, which provided a set of promising virtual drugs. Moreover, we further modified the above mentioned VCL to include the single bond linker -C-N- or -N-C-. This allowed increasing compound stability but expanded also the diversity between the available molecular probes and virtual targets. The application of the CoMSA with SOM indicated important differences between such compounds and active molecular probes. We synthesized such compounds to verify the computational predictions.

  11. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation

    Science.gov (United States)

    Connell, Bridgette Janine; Chang, Sui-Yuan; Prakash, Ekambaranellore; Yousfi, Rahima; Mohan, Viswaraman; Posch, Wilfried; Wilflingseder, Doris; Moog, Christiane; Kodama, Eiichi N.; Clayette, Pascal; Lortat-Jacob, Hugues

    2016-01-01

    Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1–7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1. PMID:27788205

  12. Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2001-09-01

    Full Text Available Abstract Background Cellulose acetate phthalate (CAP, a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1 and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1 and 2 (HSV-2 and the major nonviral sexually transmitted disease (STD pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. Methods Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. Results 1 CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2 this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3 CAP binding to HIV-1 virions impairs their infectivity; 4 these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. Conclusions These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.

  13. PVP-coated silver nanoparticles block the transmission of cell-free and cell-associated HIV-1 in human cervical culture

    Directory of Open Access Journals (Sweden)

    Rodriguez-Padilla Cristina

    2010-07-01

    Full Text Available Abstract Background Previous in vitro studies have demonstrated that polyvinylpyrrolidone coated silver nanoparticles (PVP-coated AgNPs have antiviral activity against HIV-1 at non-cytotoxic concentrations. These particles also demonstrate broad spectrum virucidal activity by preventing the interaction of HIV-1 gp120 and cellular CD4, thereby inhibiting fusion or entry of the virus into the host cell. In this study, we evaluated the antiviral activity of PVP-coated AgNPs as a potential topical vaginal microbicide to prevent transmission of HIV-1 infection using human cervical culture, an in vitro model that simulates in vivo conditions. Results When formulated into a non-spermicidal gel (Replens at a concentration of 0.15 mg/mL, PVP-coated AgNPs prevented the transmission of cell-associated HIV-1 and cell-free HIV-1 isolates. Importantly, PVP-coated AgNPs were not toxic to the explant, even when the cervical tissues were exposed continuously to 0.15 mg/mL of PVP-coated AgNPs for 48 h. Only 1 min of PVP-coated AgNPs pretreatment to the explant was required to prevent transmission of HIV-1. Pre-treatment of the cervical explant with 0.15 mg/mL PVP-coated AgNPs for 20 min followed by extensive washing prevented the transmission of HIV-1 in this model for 48 h. Conclusions A formulation of PVP-coated AgNPs homogenized in Replens gel acts rapidly to inhibit HIV-1 transmission after 1 min and offers long-lasting protection of the cervical tissue from infection for 48 h, with no evidence of cytotoxicity observed in the explants. Based on this data, PVP-coated AgNPs are a promising microbicidal candidate for use in topical vaginal/cervical agents to prevent HIV-1 transmission, and further research is warranted.

  14. Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG

    Science.gov (United States)

    2013-05-28

    Bangkok 10400, Thailand; iArmed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand; jClinical Tropical Medicine, Mahidol University... Bangkok 10400, Thailand; kDepartment of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand; and lUS Military HIV Research Program...HIV-vaccine efficacy. J Infect Dis 196(11):1637–1644. 20. Nitayaphan S, et al.; Thai AIDS Vaccine Evaluation Group (2004) Safety and immuno- genicity

  15. The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

    OpenAIRE

    1998-01-01

    The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the Caucasian population and results in a receptor protein that is truncated and not expressed at the cell surface. CCR5Δ32 homozygous individuals are apparently normal but resistant to infection with R5 HIV-1. In two individuals homozygous for CCR5Δ32, who had been repeatedly exposed to CCR5-expressing blood ...

  16. Rock blocks

    OpenAIRE

    Turner, W.

    2007-01-01

    Consider representation theory associated to symmetric groups, or to Hecke algebras in type A, or to q-Schur algebras, or to finite general linear groups in non-describing characteristic. Rock blocks are certain combinatorially defined blocks appearing in such a representation theory, first observed by R. Rouquier. Rock blocks are much more symmetric than general blocks, and every block is derived equivalent to a Rock block. Motivated by a theorem of J. Chuang and R. Kessar in the case of sym...

  17. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  18. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  19. Improving Adaptive and Memory Immune Responses of an HIV/AIDS Vaccine Candidate MVA-B by Deletion of Vaccinia Virus Genes (C6L and K7R) Blocking Interferon Signaling Pathways.

    Science.gov (United States)

    García-Arriaza, Juan; Arnáez, Pilar; Gómez, Carmen E; Sorzano, Carlos Óscar S; Esteban, Mariano

    2013-01-01

    Poxvirus vector Modified Vaccinia Virus Ankara (MVA) expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (termed MVA-B) is a promising HIV/AIDS vaccine candidate, as confirmed from results obtained in a prophylactic phase I clinical trial in humans. To improve the immunogenicity elicited by MVA-B, we have generated and characterized the innate immune sensing and the in vivo immunogenicity profile of a vector with a double deletion in two vaccinia virus (VACV) genes (C6L and K7R) coding for inhibitors of interferon (IFN) signaling pathways. The innate immune signals elicited by MVA-B deletion mutants (MVA-B ΔC6L and MVA-B ΔC6L/K7R) in human macrophages and monocyte-derived dendritic cells (moDCs) showed an up-regulation of the expression of IFN-β, IFN-α/β-inducible genes, TNF-α, and other cytokines and chemokines. A DNA prime/MVA boost immunization protocol in mice revealed that these MVA-B deletion mutants were able to improve the magnitude and quality of HIV-1-specific CD4(+) and CD8(+) T cell adaptive and memory immune responses, which were mostly mediated by CD8(+) T cells of an effector phenotype, with MVA-B ΔC6L/K7R being the most immunogenic virus recombinant. CD4(+) T cell responses were mainly directed against Env, while GPN-specific CD8(+) T cell responses were induced preferentially by the MVA-B deletion mutants. Furthermore, antibody levels to Env in the memory phase were slightly enhanced by the MVA-B deletion mutants compared to the parental MVA-B. These findings revealed that double deletion of VACV genes that act blocking intracellularly the IFN signaling pathway confers an immunological benefit, inducing innate immune responses and increases in the magnitude, quality and durability of the HIV-1-specific T cell immune responses. Our observations highlighted the immunomodulatory role of the VACV genes C6L and K7R, and that targeting common pathways, like IRF3/IFN-β signaling, could be a general strategy to improve the immunogenicity

  20. Improving Adaptive and Memory Immune Responses of an HIV/AIDS Vaccine Candidate MVA-B by Deletion of Vaccinia Virus Genes (C6L and K7R Blocking Interferon Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Juan García-Arriaza

    Full Text Available Poxvirus vector Modified Vaccinia Virus Ankara (MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (termed MVA-B is a promising HIV/AIDS vaccine candidate, as confirmed from results obtained in a prophylactic phase I clinical trial in humans. To improve the immunogenicity elicited by MVA-B, we have generated and characterized the innate immune sensing and the in vivo immunogenicity profile of a vector with a double deletion in two vaccinia virus (VACV genes (C6L and K7R coding for inhibitors of interferon (IFN signaling pathways. The innate immune signals elicited by MVA-B deletion mutants (MVA-B ΔC6L and MVA-B ΔC6L/K7R in human macrophages and monocyte-derived dendritic cells (moDCs showed an up-regulation of the expression of IFN-β, IFN-α/β-inducible genes, TNF-α, and other cytokines and chemokines. A DNA prime/MVA boost immunization protocol in mice revealed that these MVA-B deletion mutants were able to improve the magnitude and quality of HIV-1-specific CD4(+ and CD8(+ T cell adaptive and memory immune responses, which were mostly mediated by CD8(+ T cells of an effector phenotype, with MVA-B ΔC6L/K7R being the most immunogenic virus recombinant. CD4(+ T cell responses were mainly directed against Env, while GPN-specific CD8(+ T cell responses were induced preferentially by the MVA-B deletion mutants. Furthermore, antibody levels to Env in the memory phase were slightly enhanced by the MVA-B deletion mutants compared to the parental MVA-B. These findings revealed that double deletion of VACV genes that act blocking intracellularly the IFN signaling pathway confers an immunological benefit, inducing innate immune responses and increases in the magnitude, quality and durability of the HIV-1-specific T cell immune responses. Our observations highlighted the immunomodulatory role of the VACV genes C6L and K7R, and that targeting common pathways, like IRF3/IFN-β signaling, could be a general strategy to improve the

  1. Zitongdong Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ The Zitongdong Block (Eastern Zitong Block) is located in the northwest of the Sichuan Basin. Tectonically, it is situated in the east part of Zitong Depression, southeast of mid-Longmenshan folded and faulted belt( as shown on Fig. 8 ), covering an area of 1 730 km2. The traffic is very convenient, the No. 108 national highway passes through the north of the block. Topographically, the area belongs to low hilly land at the elevation of 500-700 m.

  2. HIV Transmission

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... on HIV Syndicated Content Website Feedback HIV/AIDS HIV Transmission Language: English (US) Español (Spanish) Recommend ...

  3. 抗病毒治疗阻断HIV家庭内传播的研究进展%Progress in antiretroviral therapy for blocking HIV transmission in HIV-discordant couples

    Institute of Scientific and Technical Information of China (English)

    冯孟贤; 刘民; 刘珏; 陈京

    2015-01-01

    目前抗病毒治疗(ART)阻断艾滋病病毒(HIV)家庭内传播的研究有系统综述和Meta分析、随机对照实验、队列研究及病例对照研究等多种方法.多项研究证明,ART具有阻断HIV家庭内传播的效果,并且该效果受到感染者性别、ART的治疗时机、HIV病毒载量、ART的治疗持续时间、更换治疗方案、配偶间性行为情况等因素的影响.因此HIV家庭内预防工作应采取综合防治措施.

  4. Zitongxi Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ Zitongxi Block (Western Zitong Block), is located in Zitong County, northwest of Sichuan Province (as shown on Fig. 8 ). Geologically. it is situated in the Zitong Depression, southwest of the middle Longmenshan faulted and folded belt, covering an area of 1 830 km2. Transportation is very convenient. A crisscross network of highways run through the block and the Baocheng railway is nearby. The climate is moderate. Most area belongs to hilly land with the elevation of 500-600 m.The Tongjiang River runs across the area.

  5. Chengzikou Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ Chengzikou Block is located in the north of Hekou district, Dongying City, Shandong Province, adjacent to Bohai Bay. It can be geographically divided into three units: onshore, transitional zone and offshore ultrashallow zone, totally covering an area of 470 km2. The southern onshore area is low and gentle in topography;the northern shallow sea is at water depths of 2-8 m below sea level, and the transitional zone occupies more than 60% of the whole block. The climate belongs to temperate zone with seasonal wind. Highways are welldeveloped here, and the traffic is very convenient. The Chengzikou Block is about 80 km away from Dongying City and 290 km from Jinan City in the south. The northern offshore area of the block is 160 km away from Longkou port in the east and only 38 km away in the west from Zhuangxi port.

  6. Longmenshan Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ Longmenshan Block is located in Jiange County of Jiangyou City in the northwest of Sichuan Basin. covering an area of 2 628 km2. Geologically, it is situated in the Mid-Longmenshan fault and fold belt, neighbouring Zitong Depression in its southeast. There are mountains surrounding its northwest , the rest area being hilly land,with the elevation of 500-700 m. The BaoCheng railway and the No. 108 highway run through the block, the traffic is very convenient.

  7. HIV-1 gp120单克隆抗体体外阻断CD4细胞HIV感染的研究%Study of HIV-1 gp120 monoclonal antibody blocking HIV infection of CD4 lymphocyte in vitro experiment

    Institute of Scientific and Technical Information of China (English)

    赵磊; 赵伟; 张永成; 张亮; 文剑

    2010-01-01

    目的:抗HIV-1 gp120单克隆抗体对细胞感染HIV的拮抗作用研究.方法:制备抗HIV-1 gp120单克隆抗体,鉴定其特性;研究抗HIV-1 gp120单克隆抗体对细胞感染HIV的拮抗作用.结果:构建的重组质粒的外源基因片段经测序与预期HIV-1 gp120抗原基因片段大小一致;高浓度时该单克隆抗体能够抑制HIV病毒的感染,随着抗体浓度的降低,中和实验的抑制率也随之下降;高浓度时该单克隆抗体能够显著抑制病毒的感染,随着抗体浓度的降低,HIV gp120 RNA定量增高.结论:获得6株稳定分泌抗HIV-1 gp120单克隆抗体的杂交瘤细胞株,该抗HIV-1 gp120单克隆抗体具有一定的抗HIV作用.

  8. HIV-1 and HIV-2 LTR nucleotide sequences: assessment of the alignment by N-block presentation, "retroviral signatures" of overrepeated oligonucleotides, and a probable important role of scrambled stepwise duplications/deletions in molecular evolution.

    Science.gov (United States)

    Laprevotte, I; Pupin, M; Coward, E; Didier, G; Terzian, C; Devauchelle, C; Hénaut, A

    2001-07-01

    Previous analyses of retroviral nucleotide sequences, suggest a so-called "scrambled duplicative stepwise molecular evolution" (many sectors with successive duplications/deletions of short and longer motifs) that could have stemmed from one or several starter tandemly repeated short sequence(s). In the present report, we tested this hypothesis by focusing on the long terminal repeats (LTRs) (and flanking sequences) of 24 human and 3 simian immunodeficiency viruses. By using a calculation strategy applicable to short sequences, we found consensus overrepresented motifs (often containing CTG or CAG) that were congruent with the previously defined "retroviral signature." We also show many local repetition patterns that are significant when compared with simply shuffled sequences. First- and second-order Markov chain analyses demonstrate that a major portion of the overrepresented oligonucleotides can be predicted from the dinucleotide compositions of the sequences, but by no means can biological mechanisms be deduced from these results: some of the listed local repetitions remain significant against dinucleotide-conserving shuffled sequences; together with previous results, this suggests that interspersed and/or local mononucleotide and oligonucleotide repetitions could have biased the dinucleotide compositions of the sequences. We searched for suggestive evolutionary patterns by scrutinizing a reliable multiple alignment of the 27 sequences. A manually constructed alignment based on homology blocks was in good agreement with the polypeptide alignment in the coding sectors and has been exhaustively assessed by using a multiplied alphabet obtained by the promising mathematical strategy called the N-block presentation (taking into account the environment of each nucleotide in a sequence). Sector by sector, we hypothesize many successive duplication/deletion scenarios that fit our previous evolutionary hypotheses. This suggests an important duplication/deletion role for

  9. Chadong Block

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ The Chadong Block, located in the east of Qaidam Basin, Qinghai Province, covers an area of 12 452 km2. It is bounded by Kunlum Mountains in the south and the northwest is closely adjacent to Aimunike Mountain.Rivers are widely distributed, which always run in NWSE direction, including the Sulunguole, Qaidam and Haluwusu Rivers. The traffic condition is good, the Qinghai-Tibet highway stretching through the whole area and the Lan-Qing railway, 20-50 km away from the block, passing from north to west. A lot of Mongolia minority people have settled there, of which herdsmen always live nearby the Qaidam River drainage area.

  10. HIV Testing

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... All Collapse All Should I get tested for HIV? CDC recommends that everyone between the ages of ...

  11. HIV Prevention

    Science.gov (United States)

    ... on HIV Syndicated Content Website Feedback HIV/AIDS Prevention Language: English (US) Español (Spanish) Recommend on ... All Is abstinence the only 100% effective HIV prevention option? Yes. Abstinence means not having oral, vaginal, ...

  12. Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Olofsson, S;

    1994-01-01

    In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism.......In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism....

  13. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV Share Tweet Linkedin Pin it More sharing options ... HIV? What should pregnant women know about HIV? HIV Quick Facts What is HIV? HIV is the ...

  14. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  15. HIV Treatment: The Basics

    Science.gov (United States)

    HIV Treatment HIV Treatment: The Basics (Last updated 2/24/2017; last reviewed 2/24/2017) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  16. HIV/AIDS Treatment

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin HIV/AIDS Treatment HIV/AIDS HIV/AIDS Vaccine Development ... such as hepatitis, malaria, and tuberculosis. Treatment of HIV Infection In the early 1980s when the HIV/ ...

  17. Kinetic studies of HIV-1 and HIV-2 envelope glycoprotein-mediated fusion

    Directory of Open Access Journals (Sweden)

    Doms Robert W

    2006-12-01

    Full Text Available Abstract Background HIV envelope glycoprotein (Env-mediated fusion is driven by the concerted coalescence of the HIV gp41 N-helical and C-helical regions, which results in the formation of 6 helix bundles. Kinetics of HIV Env-mediated fusion is an important determinant of sensitivity to entry inhibitors and antibodies. However, the parameters that govern the HIV Env fusion cascade have yet to be fully elucidated. We address this issue by comparing the kinetics HIV-1IIIB Env with those mediated by HIV-2 from two strains with different affinities for CD4 and CXCR4. Results HIV-1 and HIV-2 Env-mediated cell fusion occurred with half times of about 60 and 30 min, respectively. Binding experiments of soluble HIV gp120 proteins to CD4 and co-receptor did not correlate with the differences in kinetics of fusion mediated by the three different HIV Envs. However, escape from inhibition by reagents that block gp120-CD4 binding, CD4-induced CXCR4 binding and 6-helix bundle formation, respectively, indicated large difference between HIV-1 and HIV-2 envelope glycoproteins in their CD4-induced rates of engagement with CXCR4. Conclusion The HIV-2 Env proteins studied here exhibited a significantly reduced window of time between the engagement of gp120 with CD4 and exposure of the CXCR4 binding site on gp120 as compared with HIV-1IIIB Env. The efficiency with which HIV-2 Env undergoes this CD4-induced conformational change is the major cause of the relatively rapid rate of HIV-2 Env mediated-fusion.

  18. Novel Approaches to Inhibit HIV Entry

    Directory of Open Access Journals (Sweden)

    Chukwuka A. Didigu

    2012-02-01

    Full Text Available Human Immunodeficiency Virus (HIV entry into target cells is a multi-step process involving binding of the viral glycoprotein, Env, to its receptor CD4 and a coreceptor—either CCR5 or CXCR4. Understanding the means by which HIV enters cells has led to the identification of genetic polymorphisms, such as the 32 base-pair deletion in the ccr5 gene (ccr5∆32 that confers resistance to infection in homozygous individuals, and has also resulted in the development of entry inhibitors—small molecule antagonists that block infection at the entry step. The recent demonstration of long-term control of HIV infection in a leukemic patient following a hematopoietic stem cell transplant using cells from a ccr5∆32 homozygous donor highlights the important role of the HIV entry in maintaining an established infection and has led to a number of attempts to treat HIV infection by genetically modifying the ccr5 gene. In this review, we describe the HIV entry process and provide an overview of the different classes of approved HIV entry inhibitors while highlighting novel genetic strategies aimed at blocking HIV infection at the level of entry.

  19. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

    Directory of Open Access Journals (Sweden)

    Nicholas F Parrish

    Full Text Available Sexual transmission of human immunodeficiency virus type 1 (HIV-1 most often results from productive infection by a single transmitted/founder (T/F virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20 and chronic (n = 20 Env constructs as well as full-length T/F (n = 6 and chronic (n = 4 infectious molecular clones (IMCs. We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.

  20. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    Science.gov (United States)

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care.

  1. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  2. Developing a Successful HIV Vaccine.

    Science.gov (United States)

    Gallo, Robert C

    2015-07-15

    Human immunodeficiency virus (HIV) genome integration indicates that persistent sterilizing immunity will be needed for a successful vaccine candidate. This suggests a need for broad antibodies targeting the Env protein. Immunogens targeting gp120 have been developed that block infection in monkeys and mimic the modest success of the RV144 clinical trial in that protection is short-lived following a decline in antibody-depending cell-mediated cytotoxicity-like antibodies. Attempts to induce antibody persistence have been complicated by a loss of efficacy, presumably by increasing the number of HIV-target cells. The key seems to be achieving an immune balance.

  3. 17β-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha.

    Science.gov (United States)

    Tasker, Carley; Ding, Jian; Schmolke, Mirco; Rivera-Medina, Amariliz; García-Sastre, Adolfo; Chang, Theresa L

    2014-05-01

    Estrogen has been shown to increase resistance to HIV/SIV transmission by increasing the thickness of the genital epithelium. The immunological role of estrogen in HIV infection of primary target cells is less well characterized. We have found that primary macrophages are a target for anti-HIV activity of 17β-estradiol (E2). E2 did not affect surface expression of CD4 and HIV co-receptors nor HIV attachment to monocyte-derived macrophages (MDMs). In addition, E2 treatment blocked infection by a co-receptor-independent HIV-1VSV-G pseudotyped virus. Quantitative polymerase chain reaction analysis of HIV reverse transcribed DNA products indicated that E2 blocked HIV reverse transcription. E2 upregulated gene expression of interferons (IFNs) in MDMs from multiple donors. However, induction of host restriction factors APOBEC3G, APOBEC3F, or SAMHD1 was not consistent, with exception of APOBEC3A. Anti-HIV activity of E2 was abolished in the presence of IFN-α neutralizing antibody, and was absent in bone marrow-derived macrophages from IFN-α receptor deficient mice. Interestingly, HIV overcame E2-mediated HIV inhibition by suppressing induction of IFNs when MDMs were exposed to HIV before E2 treatment. These results offer a new mechanism of E2 on HIV inhibition. Future studies on the interplay between HIV and E2-mediated innate immune responses will likely provide insights relevant for development of effective strategies for HIV prevention.

  4. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  5. Reversal of HIV drug resistance and novel strategies to curb HIV infection: the viral infectivity factor Vif as a target and tool of therapy.

    Science.gov (United States)

    Mezei, M; Minarovits, J

    2006-07-01

    Due to the high genetic variability of human immunodeficiency virus (HIV), treatment of AIDS (acquired immunodeficiency syndrome) patients with inhibitors of reverse trancriptase (RT) and drugs blocking the viral protease regularly results in the accumulation of drug resistant HIV variants and treatment failure. The sensitivity of clinically derived resistant HIV-1 strains to nucleotide RT inhibitors could be restored, however, in several laboratories by pharmacological depletion of the appropriate endogenous deoxynucleotide triphosphate (dNTP), and such a manipulation (induction of dCTP pool imbalance during reverse transcription in the presence of a non-nucleoside RT inhibitor) altered the mutation spectrum of the HIV-1 genome, resulting in a lower level of HIV resistance to certain drugs. The cytoplasmic single-stranded DNA cytidine deaminases APOBEC3G and APOBEC3F block HIV replication by introducing premature stop codons into the viral genome. We suggest that the resulting crippled, defective HIV (dHIV) variants could interfere with replication of "wild type" viruses and curbe disese progression in long term non-progressor individuals. Vif, an accessory protein encoded by HIV, counteracts APOBEC3G/F action. We speculate that small molecule inhibitors of Vif could permit lethal or sublethal mutagenesis of HIV genomes. We suggest that an artificial dHIV construct carrying a mutated vif gene (coding for a Vif protein unable to block APOBEC3G/F) could have a therapeutic effect as well in HIV infected individuals and AIDS patients.

  6. CD4+ T cell-mediated presentation of non-infectious HIV-1virion antigens to HIV-specific CD8+ T cells

    Institute of Scientific and Technical Information of China (English)

    XU Jian-qing; Franco Lori; Julianna Lisziewicz

    2006-01-01

    Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals.Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens.Results CD4+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8+ T cells. Cross presentation required the entry of HIV-1 to CD4+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4+mediated activation of HIV-specific CD8+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses.Conclusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4+ T cells cross presenting HIV-1 antigen to activate CD8+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1. Virions play a role in the immunopathogenesis of HIV-1 infection.

  7. TIM-family proteins inhibit HIV-1 release.

    Science.gov (United States)

    Li, Minghua; Ablan, Sherimay D; Miao, Chunhui; Zheng, Yi-Min; Fuller, Matthew S; Rennert, Paul D; Maury, Wendy; Johnson, Marc C; Freed, Eric O; Liu, Shan-Lu

    2014-09-02

    Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV-1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors.

  8. Total Spinal Block after Thoracic Paravertebral Block.

    Science.gov (United States)

    Beyaz, Serbülent Gökhan; Özocak, Hande; Ergönenç, Tolga; Erdem, Ali Fuat; Palabıyık, Onur

    2014-02-01

    Thoracic paravertebral block (TPVB) can be performed with or without general anaesthesia for various surgical procedures. TPVB is a popular anaesthetic technique due to its low side effect profile and high analgesic potency. We used 20 mL of 0.5% levobupivacaine for a single injection of unilateral TPVB at the T7 level with neurostimulator in a 63 year old patient with co-morbid disease who underwent cholecystectomy. Following the application patient lost consciousness, and was intubated. Haemodynamic instability was normalised with rapid volume replacement and vasopressors. Anaesthetic drugs were stopped at the end of the surgery and muscle relaxant was antagonised. Return of mucle strenght was shown with neuromuscular block monitoring. Approximately three hours after TPVB, spontaneous breathing started and consciousness returned. A total spinal block is a rare and life-threatening complication. A total spinal block is a complication of spinal anaesthesia, and it can also occur after peripheral blocks. Clinical presentation is characterised by hypotension, bradicardia, apnea, and cardiac arrest. An early diagnosis and appropriate treatment is life saving. In this case report, we want to present total spinal block after TPVB.

  9. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  10. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: March 2, 2017 Key ...

  11. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... 03-13T18:29:11+00:00 PH and HIV Print PH and HIV Brochure (PDF) Order Copies ... to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and HIV are two separate ...

  12. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  13. HIV and AIDS

    Science.gov (United States)

    ... Emergency Room? What Happens in the Operating Room? HIV and AIDS KidsHealth > For Kids > HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  14. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  15. HIV Medication Adherence

    Science.gov (United States)

    HIV Treatment HIV Medication Adherence (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  16. HIV and Pregnancy

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV and Pregnancy ... Pregnancy FAQ113, December 2012 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus (HIV)? How ...

  17. 4. CRIMINALISING HIV TRANSMISSION

    African Journals Online (AJOL)

    Esem

    should be adopted to expand targeted efforts in preventing new HIV infections in Zambia. ... result of sexual intercourse between an HIV positive and. HIV negative person and ..... countries have not criminalized HIV infection. To this end, those ...

  18. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes.......Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...

  19. Tannin inhibits HIV-1 entry by targeting gp41

    Institute of Scientific and Technical Information of China (English)

    Lin L(U); Shu-wen LIU; Shi-bo JIANG; Shu-guang WU

    2004-01-01

    AIM: To investigate the mechanism by which tannin inhibits HIV-1 entry into target cells. METHODS: The inhibitory activity of tannin on HIV-1 replication and entry was detected by p24 production and HIV-1-mediated cell fusion, respectively. The inhibitory activity on the gp41 six-helix bundle formation was determined by an improved sandwich ELISA. RESULTS: Tannins from different sources showed potent inhibitory activity on HIV-1 replication,HIV-1-mediated cell fusion, and the gp4 six-helix bundle formation. CONCLUSION: Tannin inhibits HIV-1 entry into target cells by interfering with the gp41 six-helix bundle formation, thus blocking HIV-1 fusion with the target cell.

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  2. HIV among Women

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Women Format: Select One File [155K] Recommend ...

  3. HIV among Transgender People

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Transgender People Format: Select One PDF [227K] ...

  4. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English (US) Español (Spanish) Recommend on ...

  5. HIV Among Asians

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Asians in the United States Format: Select ...

  6. BLOCK H-MATRICES AND SPECTRUM OF BLOCK MATRICES

    Institute of Scientific and Technical Information of China (English)

    黄廷祝; 黎稳

    2002-01-01

    The block H-matrices are studied by the concept of G-functions, several concepts of block matrices are introduced. Equivalent characters of block H-matrices are obtained. Spectrum localizations claracterized by Gfunctions for block matrices are got.

  7. Block TERM factorization of block matrices

    Institute of Scientific and Technical Information of China (English)

    SHE Yiyuan; HAO Pengwei

    2004-01-01

    Reversible integer mapping (or integer transform) is a useful way to realize Iossless coding, and this technique has been used for multi-component image compression in the new international image compression standard JPEG 2000. For any nonsingular linear transform of finite dimension, its integer transform can be implemented by factorizing the transform matrix into 3 triangular elementary reversible matrices (TERMs) or a series of single-row elementary reversible matrices (SERMs). To speed up and parallelize integer transforms, we study block TERM and SERM factorizations in this paper. First, to guarantee flexible scaling manners, the classical determinant (det) is generalized to a matrix function, DET, which is shown to have many important properties analogous to those of det. Then based on DET, a generic block TERM factorization,BLUS, is presented for any nonsingular block matrix. Our conclusions can cover the early optimal point factorizations and provide an efficient way to implement integer transforms for large matrices.

  8. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  9. Lesson Thirteen Trifascicular Block

    Institute of Scientific and Technical Information of China (English)

    鲁端; 王劲

    2005-01-01

    @@ A complete trifascicular block would result in complete AV block. The idio ventricular rhythm has a slower rate and a wide QRS complex because the pacemaker is located at the peripheral part of the conduction system distal to the sites of the block1. Such a rhythm may be difficult to differentiate from bifascicular or bundle branch block combined with complete block at a higher level such as the AV node or His bundle2. Besides a slower ventricular rate, a change in the morphology of the QRS complex from a previous known bifascicular pattern would be strongly suggestive of a trifascicular origin of the complete AV block3. A His bundle recording is required for a definitive diagnosis, however.

  10. A novel peptide that inhibits HIV-1 entry

    Institute of Scientific and Technical Information of China (English)

    YU Yong; HUANG Xiaoxing; WANG Qiong; YANG Yaling; TIAN Po; ZHANG Wentao

    2004-01-01

    @@ The global epidemic of HIV infection, the cause of AIDS, has created an urgent need for novel classes of antiretroviral agent. Besides reverse transcriptase and protease, the viral entry process provides new anti-HIV-1 targets. A new generation of antiviral drugs intended to block HIV entry into host cells is now under develop- ment[1]. These compounds are generally referred to as fusion or entry inhibitor. Several HIV-1 entry inhibitors that target CD4-gp120 interactions, co-receptor function, and gp41-mediated membrane fusion are in different stages of clinical development[2].

  11. Convenient cell fusion assay for rapid screening for HIV entry inhibitors

    Science.gov (United States)

    Jiang, Shibo; Radigan, Lin; Zhang, Li

    2000-03-01

    Human immunodeficiency viruses (HIV)-induced cell fusion is a critical pathway of HIV spread from infected cells to uninfected cells. A rapid and simple assay was established to measure HIV-induce cell fusion. This study is particularly useful to rapid screen for HIV inhibitors that block HIV cell-to-cell transmission. Present study demonstrated that coculture of HIV-infected cells with uninfected cells at 37 degree(s)C for 2 hours resulted in the highest cell fusion rate. Using this cell fusion assay, we have identified several potent HIV inhibitors targeted to the HIV gp41 core. These antiviral agents can be potentially developed as antiviral drugs for chemotherapy and prophylaxis of HIV infection and AIDS.

  12. Blocked Urethral Valves

    Science.gov (United States)

    ... Blocked Urethral Valves Health Issues Listen Español Text Size Email Print Share Blocked Urethral Valves Page Content Article Body Urine leaves the bladder through a tube called the urethra, which in boys passes through the penis. Rarely, small membranes form across the urethra in ...

  13. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix. Inde

  14. Types of Heart Block

    Science.gov (United States)

    ... P wave as it normally would. If an electrical signal is blocked before it reaches the ventricles, they won't contract and pump blood to the lungs and the rest of the body. Second-degree heart block is divided into two ...

  15. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix. Inde

  16. The Block Neighborhood

    CERN Document Server

    Arrighi, Pablo

    2010-01-01

    We define the block neighborhood of a reversible CA, which is related both to its decomposition into a product of block permutations and to quantum computing. We give a purely combinatorial characterization of the block neighborhood, which helps in two ways. First, it makes the computation of the block neighborhood of a given CA relatively easy. Second, it allows us to derive upper bounds on the block neighborhood: for a single CA as function of the classical and inverse neighborhoods, and for the composition of several CAs. One consequence of that is a characterization of a class of "elementary" CAs that cannot be written as the composition of two simpler parts whose neighborhoods and inverse neighborhoods would be reduced by one half.

  17. Antiretroviral therapy to block transmission in HIV discordant couples: a meta-analysis%抗病毒治疗阻断HIV单阳家庭内传播效果的Meta分析

    Institute of Scientific and Technical Information of China (English)

    冯孟贤; 刘民; 刘珏; 陈京

    2015-01-01

    目的 通过Meta分析,了解抗病毒治疗(ART)阻断艾滋病病毒(HIV)单阳家庭内传播的效果.方法 系统检索PubMed、Ovid、Web of science、Cochrane Central Register of Controlled Trials、CNKI、万方、维普等数据库,检索时间为1987年1月至2014年8月,纳入有关HIV阳性配偶ART阻断家庭内传播的文献,评价指标为家庭内传播的相对危险度(RR).采用Stata软件进行异质性检验,计算合并RR值及其95%可信区间(CI)值,并根据性别、CD+T淋巴细胞(简称CD4细胞)水平及国家收入水平进行亚组分析.结果 共纳入16篇文献,包括1篇随机对照试验研究和15篇队列研究.Meta分析显示:ART阻断单阳家庭内传播的合并效应量RR=0.36(95%CI:0.26~0.50),表明与没有接受ART的单阳家庭相比,ART使HIV家庭内传播风险降低64%.亚组分析显示,与未治疗组相比,ART可使单阳家庭内男传女、女传男的风险分别降低63%和25%;在CD4细胞<200个/μL、200~350个/μL、>350个/μL时开始ART治疗,家庭内传播的风险分别降低74%、34%和59%;ART使中低收入国家和高收入国家人群的HIV家庭内传播风险分别降低66%和27%.结论 抗病毒治疗可以降低HIV单阳家庭内传播的风险.并且对男传女的阻断效果优于女传男的家庭;当CD4细胞>350个/μL或者<200个/μL时,开始治疗的阻断效果优于CD4细胞200~350个/μL时;中低收入国家人群的阻断效果优于高收入国家.

  18. Natural Plant Alkaloid (Emetine Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity

    Directory of Open Access Journals (Sweden)

    Ana Luiza Chaves Valadão

    2015-06-01

    Full Text Available Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V. Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.

  19. HIV Life Cycle

    Science.gov (United States)

    HIV Overview The HIV Life Cycle (Last updated 9/13/2016; last reviewed 9/8/2016) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  20. HIV Latency

    OpenAIRE

    Robert F. Siliciano; Greene, Warner C.

    2011-01-01

    HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4+ T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recogni...

  1. Screening and diagnosis for HIV

    Science.gov (United States)

    HIV testing; HIV screening; HIV screening test; HIV confirmatory test ... Task Force. Final Update Summary: Human Immunodeficiency Virus (HIV) Infection: Screening. July 2015. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/ ...

  2. Block copolymer battery separator

    Energy Technology Data Exchange (ETDEWEB)

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  3. Hawaii Census 2000 Blocks

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data layer represents Census 2000 demographic data derived from the PL94-171 redistricting files and SF3. Census geographic entities include blocks, blockgroups...

  4. Using the Stern Blocks.

    Science.gov (United States)

    Stern, Margaret

    1987-01-01

    Extracts from "Experimenting with Numbers" by Margaret Stern demonstrate the use of Stern Blocks to develop the conceptual base on which learning disabled students can build further mathematical skills. (DB)

  5. Steroidal neuromuscular blocking agents

    NARCIS (Netherlands)

    Wierda, JMKH; Mori, K; Ohmura, A; Toyooka, H; Hatano, Y; Shingu, K; Fukuda, K

    1998-01-01

    Since 1964 approximately 20 steroidal neuromuscular blocking agents have been evaluated clinically. Pancuronium, a bisquaternary compound designed on the drawingboard, was the first steroidal relaxant introduced into clinical practice worldwide in the 1970's. Although a major improvement, pancuroniu

  6. Block copolymer battery separator

    Science.gov (United States)

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  7. Recipient block TMA technique.

    Science.gov (United States)

    Mirlacher, Martina; Simon, Ronald

    2010-01-01

    New high-throughput screening technologies have led to the identification of hundreds of genes with a potential role in cancer or other diseases. One way to prioritize the leads obtained in such studies is to analyze a large number of tissues for candidate gene expression. The TMA methodology is now an established and frequently used tool for high-throughput tissue analysis. The recipient block technology is the "classical" method of TMA making. In this method, minute cylindrical tissue punches typically measuring 0.6 mm in diameter are removed from donor tissue blocks and are transferred into empty "recipient" paraffin blocks. Up to 1,000 different tissues can be analyzed in one TMA block. The equipment is affordable and easy to use in places where basic skills in histology are available.

  8. Superalloy Lattice Block Structures

    Science.gov (United States)

    Nathal, M. V.; Whittenberger, J. D.; Hebsur, M. G.; Kantzos, P. T.; Krause, D. L.

    2004-01-01

    Initial investigations of investment cast superalloy lattice block suggest that this technology will yield a low cost approach to utilize the high temperature strength and environmental resistance of superalloys in lightweight, damage tolerant structural configurations. Work to date has demonstrated that relatively large superalloy lattice block panels can be successfully investment cast from both IN-718 and Mar-M247. These castings exhibited mechanical properties consistent with the strength of the same superalloys measured from more conventional castings. The lattice block structure also accommodates significant deformation without failure, and is defect tolerant in fatigue. The potential of lattice block structures opens new opportunities for the use of superalloys in future generations of aircraft applications that demand strength and environmental resistance at elevated temperatures along with low weight.

  9. Block Cipher Analysis

    DEFF Research Database (Denmark)

    Miolane, Charlotte Vikkelsø

    ensurethat no attack violatesthe securitybounds specifiedbygeneric attack namely exhaustivekey search and table lookup attacks. This thesis contains a general introduction to cryptography with focus on block ciphers and important block cipher designs, in particular the Advanced Encryption Standard...... by an analytic and systematic approach that allows insight to the techniques. Moreover a new procedure of generating and applying probabilistic equations in algebraic attacks on block cipher is proposed and examined. Also, we present practical results, which to our knowledge are the best algebraic results...... on small scale variants of AES. In the final part of the thesis we present a new block cipher proposal Present and examine its security against algebraic and differential cryptanalysis in particular....

  10. Tetherin does not significantly restrict dendritic cell-mediated HIV-1 transmission and its expression is upregulated by newly synthesized HIV-1 Nef

    Directory of Open Access Journals (Sweden)

    Wu Li

    2011-04-01

    Full Text Available Abstract Background Dendritic cells (DCs are among the first cells to encounter HIV-1 and play important roles in viral transmission and pathogenesis. Immature DCs allow productive HIV-1 replication and long-term viral dissemination. The pro-inflammatory factor lipopolysaccharide (LPS induces DC maturation and enhances the efficiency of DC-mediated HIV-1 transmission. Type I interferon (IFN partially inhibits HIV-1 replication and cell-cell transmission in CD4+ T cells and macrophages. Tetherin is a type I IFN-inducible restriction factor that blocks HIV-1 release and modulates CD4+ T cell-mediated cell-to-cell transmission of HIV-1. However, the role of type I IFN and tetherin in HIV-1 infection of DCs and DC-mediated viral transmission remains unknown. Results We demonstrated that IFN-alpha (IFNα-induced mature DCs restricted HIV-1 replication and trans-infection of CD4+ T cells. Tetherin expression in monocyte-derived immature DCs was undetectable or very low. High levels of tetherin were transiently expressed in LPS- and IFNα-induced mature DCs, while HIV-1 localized into distinct patches in these DCs. Knockdown of induced tetherin in LPS- or IFNα-matured DCs modestly enhanced HIV-1 transmission to CD4+ T cells, but had no significant effect on wild-type HIV-1 replication in mature DCs. Intriguingly, we found that HIV-1 replication in immature DCs induced significant tetherin expression in a Nef-dependent manner. Conclusions The restriction of HIV-1 replication and transmission in IFNα-induced mature DCs indicates a potent anti-HIV-1 response; however, high levels of tetherin induced in mature DCs cannot significantly restrict wild-type HIV-1 release and DC-mediated HIV-1 transmission. Nef-dependent tetherin induction in HIV-1-infected immature DCs suggests an innate immune response of DCs to HIV-1 infection.

  11. HIV and Immunizations

    Science.gov (United States)

    HIV Treatment HIV and Immunizations (Last updated 2/24/2017; last reviewed 2/24/2017) Key Points Vaccines protect people from ... a disease outbreak. Is there a vaccine against HIV? Testing is underway on experimental vaccines to prevent ...

  12. Children and HIV

    Science.gov (United States)

    ... Subscribe Translate Text Size Print Children Children and HIV Most HIV-positive children under the age of ... Frequently Asked Questions How long do children with HIV typically live? Because effective treatments are relatively new ...

  13. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Laotian Mongolian Spanish Turkish Vietnamese Hindi Subscribe HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  14. HIV and Hepatitis B

    Science.gov (United States)

    ... to-Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: ... sexual contact. According to the Centers for Disease Control and Prevention (CDC) , approximately 10% of people with ...

  15. Epitope target structures of Fc-mediated effector function during HIV-1 acquisition.

    Science.gov (United States)

    Lewis, George K; Guan, Yongjun; Kamin-Lewis, Roberta; Sajadi, Mohammad; Pazgier, Marzena; Devico, Anthony L

    2014-05-01

    This review analyzes recent studies suggesting that highly conserved epitopes in the HIV-1 Env trimer are targets of potentially protective nonneutralizing antibodies that mediate antibody-dependent cellular cytotoxicity. Recent studies in both non-human primates and humans suggest that nonneutralizing antibodies play a role in blocking infection with hybrid simian HIV (SHIV)/simian immunodeficiency virus (SIV) or HIV-1 by Fc-mediated effector function, in particular antibody-dependent cellular cytotoxicity. Further, several studies implicate highly conserved epitopes in the C1 region of gp120 as targets of these antibodies. However, these suggestions are controversial, as passive immunization studies do not indicate that such antibodies can block acquisition in non-human primates. Potential reasons for this discrepancy are discussed in the structural context of potent antibody-dependent cellular cytotoxicity epitopes on target cells during the narrow window of opportunity when antibodies can block HIV-1 acquisition. Cumulative evidence suggests that, in addition to virus neutralization, Fc-mediated effector responses to highly conserved epitopes in the HIV-1 trimer play distinct as well as overlapping roles in blocking HIV-1 acquisition. Evidence will be discussed as to whether nonneutralizing antibodies specific for epitopes on the HIV-1 Env trimer that become exposed during viral entry contribute significantly to blocking HIV-1 acquisition.

  16. Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Wilfried Posch

    2015-06-01

    Full Text Available DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.

  17. IFN-λ Inhibits Drug-Resistant HIV Infection of Macrophages

    Science.gov (United States)

    Wang, Xu; Wang, He; Liu, Man-Qing; Li, Jie-Liang; Zhou, Run-Hong; Zhou, Yu; Wang, Yi-Zhong; Zhou, Wang; Ho, Wen-Zhe

    2017-01-01

    Type III interferons (IFN-λs) have been demonstrated to inhibit a number of viruses, including HIV. Here, we further examined the anti-HIV effect of IFN-λs in macrophages. We found that IFN-λs synergistically enhanced anti-HIV activity of antiretrovirals [azidothymidine (AZT), efavirenz, indinavir, and enfuvirtide] in infected macrophages. Importantly, IFN-λs could suppress HIV infection of macrophages with the drug-resistant strains, including AZT-resistant virus (A012) and reverse transcriptase inhibitor-resistant virus (TC49). Mechanistically, IFN-λs were able to induce the expression of several important anti-HIV cellular factors, including myxovirus resistance 2 (Mx2), a newly identified HIV post-entry inhibitor and tetherin, a restriction factor that blocks HIV release from infected cells. These observations provide additional evidence to support the potential use of IFN-λs as therapeutics agents for the treatment of HIV infection. PMID:28321215

  18. Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

    Directory of Open Access Journals (Sweden)

    Woods Matthew W

    2011-11-01

    Full Text Available Abstract Background The identification and characterization of several interferon (IFN-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5 that blocks a unique late stage of the HIV-1 life cycle. Results HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. Conclusions HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

  19. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included.......5%/2.3% in women, P Right bundle branch block was associated with significantly...... increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated...

  20. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

    Science.gov (United States)

    Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V; Caskey, Marina; Chakraborty, Arup K; Nussenzweig, Michel C

    2016-05-20

    Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.

  1. 31 CFR 547.302 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    .... 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance... SANCTIONS REGULATIONS General Definitions § 547.302 Blocked account; blocked property. The terms blocked account and blocked property shall mean any account or property subject to the prohibitions in § 547.201...

  2. PSC-RANTES blocks R5 human immunodeficiency virus infection of Langerhans cells isolated from individuals with a variety of CCR5 diplotypes.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Bruse, Shannon E; Abraha, Awet; Sugaya, Makoto; Hartley, Oliver; Offord, Robin E; Arts, Eric J; Zimmerman, Peter A; Blauvelt, Andrew; Bruce, Shannon E

    2004-07-01

    Topical microbicides that effectively block interactions between CCR5(+) immature Langerhans cells (LC) residing within genital epithelia and R5 human immunodeficiency virus (HIV) may decrease sexual transmission of HIV. Here, we investigated the ability of synthetic RANTES analogues (AOP-, NNY-, and PSC-RANTES) to block R5 HIV infection of human immature LC by using a skin explant model. In initial experiments using activated peripheral blood mononuclear cells, each analogue compound demonstrated marked antiviral activity against two R5 HIV isolates. Next, we found that 20-min preincubation of skin explants with each RANTES analogue blocked R5 HIV infection of LC in a dose-dependent manner (1 to 100 nM) and that PSC-RANTES was the most potent of these compounds. Similarly, preincubation of LC with each analogue was able to block LC-mediated infection of cocultured CD4(+) T cells. Competition experiments between primary R5 and X4 HIV isolates showed blocking of R5 HIV by PSC-RANTES and no evidence of increased propagation of X4 HIV, data that are consistent with the specificity of PSC-RANTES for CCR5 and the CCR5(+) CXCR4(-) phenotype of immature LC. Finally, when CCR5 genetic polymorphism data were integrated with results from the in vitro LC infection studies, PSC-RANTES was found to be equally effective in inhibiting R5 HIV in LC isolated from individuals with CCR5 diplotypes known to be associated with low, intermediate, and high cell surface levels of CCR5. In summary, PSC-RANTES is a potent inhibitor of R5 HIV infection in immature LC, suggesting that it may be useful as a topical microbicide to block sexual transmission of HIV.

  3. Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase.

    Science.gov (United States)

    Paskaleva, Elena E; Lin, Xudong; Duus, Karen; McSharry, James J; Veille, Jean-Claude L; Thornber, Carol; Liu, Yanze; Lee, David Yu-Wei; Canki, Mario

    2008-01-15

    Sargassum fusiforme (Harvey) Setchell has been shown to be a highly effective inhibitor of HIV-1 infection. To identify its mechanism of action, we performed bioactivity-guided fractionation on Sargassum fusiforme mixture. Here, we report isolation of a bioactive fraction SP4-2 (S. fusiforme), which at 8 mug/ml inhibited HIV-1 infection by 86.9%, with IC50 value of 3.7 mug. That represents 230-fold enhancement of antiretroviral potency as compared to the whole extract. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5) tropic HIV-1. Specifically, 10 mug/ml SP4-2 blocked HIV-1 fusion and entry by 53%. This effect was reversed by interaction of SP4-2 with sCD4, suggesting that S. fusiforme inhibits HIV-1 infection by blocking CD4 receptor, which also explained observed inhibition of both X4 and R5-tropic HIV-1. SP4-2 also inhibited HIV-1 replication after virus entry, by directly inhibiting HIV-1 reverse transcriptase (RT) in a dose dependent manner by up to 79%. We conclude that the SP4-2 fraction contains at least two distinct and biologically active molecules, one that inhibits HIV-1 fusion by interacting with CD4 receptor, and another that directly inhibits HIV-1 RT. We propose that S. fusiforme is a lead candidate for anti-HIV-1 drug development.

  4. Sargassum fusiforme fraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase

    Directory of Open Access Journals (Sweden)

    Thornber Carol

    2008-01-01

    Full Text Available Abstract Sargassum fusiforme (Harvey Setchell has been shown to be a highly effective inhibitor of HIV-1 infection. To identify its mechanism of action, we performed bioactivity-guided fractionation on Sargassum fusiforme mixture. Here, we report isolation of a bioactive fraction SP4-2 (S. fusiforme, which at 8 μg/ml inhibited HIV-1 infection by 86.9%, with IC50 value of 3.7 μg. That represents 230-fold enhancement of antiretroviral potency as compared to the whole extract. Inhibition was mediated against both CXCR4 (X4 and CCR5 (R5 tropic HIV-1. Specifically, 10 μg/ml SP4-2 blocked HIV-1 fusion and entry by 53%. This effect was reversed by interaction of SP4-2 with sCD4, suggesting that S. fusiforme inhibits HIV-1 infection by blocking CD4 receptor, which also explained observed inhibition of both X4 and R5-tropic HIV-1. SP4-2 also inhibited HIV-1 replication after virus entry, by directly inhibiting HIV-1 reverse transcriptase (RT in a dose dependent manner by up to 79%. We conclude that the SP4-2 fraction contains at least two distinct and biologically active molecules, one that inhibits HIV-1 fusion by interacting with CD4 receptor, and another that directly inhibits HIV-1 RT. We propose that S. fusiforme is a lead candidate for anti-HIV-1 drug development.

  5. The hunt for HIV-1 integrase inhibitors.

    Science.gov (United States)

    Lataillade, Max; Kozal, Michael J

    2006-07-01

    Currently, there are three distinct mechanistic classes of antiretrovirals: inhibitors of the HIV- 1 reverse transcriptase and protease enzymes and inhibitors of HIV entry, including receptor and coreceptor binding and cell fusion. A new drug class that inhibits the HIV-1 integrase enzyme (IN) is in development and may soon be available in the clinic. IN is an attractive drug target because it is essential for a stable and productive HIV-1 infection and there is no mammalian homologue of IN. Inhibitors of integrase enzyme (INI) block the integration of viral double-stranded DNA into the host cell's chromosomal DNA. HIV-1 integration has many potential steps that can be inhibited and several new compounds that target specific integration steps have been identified by drug developers. Recently, two INIs, GS-9137 and MK-0518, demonstrated promising early clinical trial results and have been advanced into later stage trials. In this review, we describe how IN facilitates HIV-1 integration, the needed enzyme cofactors, and the resultant byproducts created during integration. Furthermore, we review the different INIs under development, their mechanism of actions, site of IN inhibition, potency, resistance patterns, and discuss the early clinical trial results.

  6. CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines.

    Science.gov (United States)

    Ito, Yoshinori; Grivel, Jean-Charles; Chen, Silvia; Kiselyeva, Yana; Reichelderfer, Patricia; Margolis, Leonid

    2004-02-01

    In infected individuals, human immunodeficiency virus type 1 (HIV-1) exist as a "swarm" of quasi species compartmentalized in tissues where individual viral variants may interact locally. We have used human lymphoid tissue, where the critical events of HIV disease occur, to study local interactions in model HIV-1 binary swarms ex vivo. We infected tissue blocks with binary mixtures consisting either of CCR5-dependent and CXCR4-dependent variants or of 2 dual-tropic HIV-1 variants, of which one is skewed to utilization of CXCR4 and the other of CCR5. HIV-1 variants that use CXCR4 suppress replication of CCR5-dependent HIV-1 variants, whereas CCR5-dependent HIV-1 variants do not affect replication of CXCR4-dependent HIV-1. CC-chemokines that inhibit replication of CCR5-dependent HIV-1 variants were up-regulated by CXCR4-dependent HIV-1, thus possibly contributing to this suppression. Tissue-specific chemokine/cytokine network modulations triggered by individual HIV-1 variants may be an important mechanism of local interactions among HIV-1 quasi species in infected tissue.

  7. Block That Pain!

    Science.gov (United States)

    ... along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major ...

  8. Concrete Block Pavements

    Science.gov (United States)

    1983-03-01

    1967, Cedergren 1974, Federal Highway .’,U .. V,47 -’":: 37 Administration 1980). Block pavements have essentially the same prob- lems with moisture...Vicksburg, Miss. Cedergren , H. R. 1974. Drainage of Highway and Airfield Pavements, John Wiley and Sons, New VOk. I Cement and Concrete Association

  9. TWIN BLOCK (Studi Pustaka

    Directory of Open Access Journals (Sweden)

    Evie Lamtiur

    2015-08-01

    Full Text Available Young patients with class II skeletal malocclusion are often found. To avoid further discrepancy of this case, myofunctional therapy is one of the options. Functional appliance often used for such treatment. Functional appliance has been modified since activator was introduced by Andresen. With its bulky shape, activator makes difficulty for patient to speak and eat. Patient unable to wear it full time due to uncomfortness and negative facial appearance. In 1977, Clark developed twin block to overcome the weakness of previous appliances. A more simple design allows patient to be more comfortable and willing to wear it longer. Twin block is myofunctional appliance to reposition the mandible forward for skeletal class II correction with retruded mandible. This paper describes the design, clinical management effects of twin block treatment and brief case presentation using twin block appliance. Similar to the study reports found, this case revealed improvement of facial appearance, decrease overjet and overbite, improvement of molar relationship and good compliance of patient.

  10. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    Korte, de A.C.J.; Brouwers, H.J.H.; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In ord

  11. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  12. HIV Structural Database

    Science.gov (United States)

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  13. The mTOR Complex Controls HIV Latency.

    Science.gov (United States)

    Besnard, Emilie; Hakre, Shweta; Kampmann, Martin; Lim, Hyung W; Hosmane, Nina N; Martin, Alyssa; Bassik, Michael C; Verschueren, Erik; Battivelli, Emilie; Chan, Jonathan; Svensson, J Peter; Gramatica, Andrea; Conrad, Ryan J; Ott, Melanie; Greene, Warner C; Krogan, Nevan J; Siliciano, Robert F; Weissman, Jonathan S; Verdin, Eric

    2016-12-14

    A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Mathematical modeling of HIV-like particle assembly in vitro.

    Science.gov (United States)

    Liu, Yuewu; Zou, Xiufen

    2017-02-22

    In vitro, the recombinant HIV-1 Gag protein can generate spherical particles with a diameter of 25-30 nm in a fully defined system. It has approximately 80 building blocks, and its intermediates for assembly are abundant in geometry. Accordingly, there are a large number of nonlinear equations in the classical model. Therefore, it is difficult to compute values of geometry parameters for intermediates and make the mathematical analysis using the model. In this work, we develop a new model of HIV-like particle assembly in vitro by using six-fold symmetry of HIV-like particle assembly to decrease the number of geometry parameters. This method will greatly reduce computational costs and facilitate the application of the model. Then, we prove the existence and uniqueness of the positive equilibrium solution for this model with 79 nonlinear equations. Based on this model, we derive the interesting result that concentrations of all intermediates at equilibrium are independent of three important parameters, including two microscopic on-rate constants and the size of nucleating structure. Before equilibrium, these three parameters influence the concentration variation rates of all intermediates. We also analyze the relationship between the initial concentration of building blocks and concentrations of all intermediates. Furthermore, the bounds of concentrations of free building blocks and HIV-like particles are estimated. These results will be helpful to guide HIV-like particle assembly experiments and improve our understanding of the assembly dynamics of HIV-like particles in vitro.

  15. [HIV and pregnancy].

    Science.gov (United States)

    Zweifel, Vineeta Bansal; Berger, Christoph; Nadal, David; Grawe, Claudia

    2014-08-01

    The use and success of antiretroviral treatment in HIV-positive people has led to a reduction of vertical transmission of HIV. Pregnancy in HIV-positive women became more common. The success of prophylactic measures has led to a dramatic change in care of HIV-positive women. Today, a HIV-positive mother giving birth to a HIV-negative child is standard of care in industrialized countries. We describe the impact of an HIV-infection in pregnancy and outline the most important diagnostic and therapeutic aspects.

  16. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  17. Dermatomyositis and HIV

    Directory of Open Access Journals (Sweden)

    Mamata Chand

    2016-12-01

    Full Text Available HIV has been linked to several autoimmune disorders since its emergence in the 1980s. By affecting different cells and pathways in the immune system, HIV induces the development of certain autoimmune diseases while prohibiting the emergence of others. Dermatomyositis has been rarely described in patients with HIV. We present a case of dermatomyositis in a patient with HIV and explore the pathogenesis of autoimmune disorders in HIV focusing on dermatomyositis.

  18. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.  Created: 6/9/2011 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 6/9/2011.

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  20. HIV/AIDS in Women

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

  1. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 ... high-risk category, emphasizes Dr. Cargill. Photo: iStock HIV and Pregnancy Are there ways to help HIV- ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 – ... and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human ...

  3. What Is HIV/AIDS?

    Science.gov (United States)

    ... AIDS? Subscribe Translate Text Size Print What Is HIV/AIDS? Human Immunodeficiency Virus (HIV) HIV stands for human immunodeficiency virus. If left ... need medical treatment to prevent death. Where DId HIV Come From? Scientists identified a type of chimpanzee ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 – ... and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human ...

  7. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Børglum, Jens; Gögenür, Ismail; Bendtsen, Thomas F

    2016-01-01

    Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.......  Recent findings Ultrasound guidance is now considered the golden standard for abdominal wall blocks in adults, even though some landmark-based blocks are still being investigated. The efficiency of USG transversus abdominis plane blocks in relation to many surgical procedures involving the abdominal wall...... been introduced with success. Future research should also investigate the effect of specific abdominal wall blocks on neuroendocrine and inflammatory stress response after surgery.  Summary USG abdominal wall blocks in adults are commonplace techniques today. Most abdominal wall blocks are assigned...

  8. Recovery from blocking between outcomes.

    Science.gov (United States)

    Wheeler, Daniel S; Miller, Ralph R

    2005-10-01

    Contemporary associative learning research largely focuses on cue competition phenomena that occur when 2 cues are paired with a common outcome. Little research has been conducted to investigate similar phenomena occurring when a single cue is trained with 2 outcomes. Three conditioned lick suppression experiments with rats assessed whether treatments known to alleviate blocking between cues would also attenuate blocking between outcomes. In Experiment 1, conditioned responding recovered from blocking between outcomes when a long retention interval was interposed between training and testing. Experiment 2 obtained recovery from blocking between outcomes when the blocking outcome was extinguished after the blocking treatment. In Experiment 3, a recovery from blocking between outcomes occurred when a reminder stimulus was presented in a novel context prior to testing. Collectively, these studies demonstrate that blocking of outcomes, like blocking of cues, appears to be caused by a deficit in the expression of an acquired association.

  9. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  10. Managing access block.

    Science.gov (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  11. E-Block: A Tangible Programming Tool with Graphical Blocks

    Directory of Open Access Journals (Sweden)

    Danli Wang

    2013-01-01

    Full Text Available This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transferred to computer by microcomputers and then translated into semantic information. The system applies wireless and infrared technologies and provides user with feedbacks on both screen and programming blocks. Preliminary user studies using observation and user interview methods are shown for E-Block's prototype. The test results prove that E-Block is attractive to children and easy to learn and use. The project also highlights potential advantages of using single chip microcomputer (SCM technology to develop tangible programming tools for children.

  12. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  13. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  14. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  15. Ear - blocked at high altitudes

    Science.gov (United States)

    High altitudes and blocked ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... eustachian tube is a connection between the middle ear (the space deep to the eardrum) and the ...

  16. Habitat Blocks and Wildlife Corridors

    Data.gov (United States)

    Vermont Center for Geographic Information — Habitat blocks are areas of contiguous forest and other natural habitats that are unfragmented by roads, development, or agriculture. Vermonts habitat blocks are...

  17. Appropriate schemata and building blocks

    Institute of Scientific and Technical Information of China (English)

    Yang Haijun; Li Minqiang

    2005-01-01

    Appropriate schemata as a novel concept to characterize building blocks are introduced, and then, the traits of appropriate schemata are presented. The effects of building blocks by search operators are analyzed. Hence, the experiments on RR-8X8 are employed to verify that appropriate schemata construct the building blocks. The validity of appropriate schemata and building blocks from the views of theory and practice is presented.

  18. Properties of blocked linear systems.

    Science.gov (United States)

    Chen, Weitian; Anderson, Brian D O; Deistler, Manfred; Filler, Alexander

    2012-10-01

    This paper presents a systematic study on the properties of blocked linear systems that have resulted from blocking discrete-time linear time invariant systems. The main idea is to explore the relationship between the blocked and the unblocked systems. Existing results are reviewed and a number of important new results are derived. Focus is given particularly on the zero properties of the blocked system as no such study has been found in the literature.

  19. Porous block nanofiber composite filters

    Energy Technology Data Exchange (ETDEWEB)

    Ginley, David S.; Curtis, Calvin J.; Miedaner, Alexander; Weiss, Alan J.; Paddock, Arnold

    2016-08-09

    Porous block nano-fiber composite (110), a filtration system (10) and methods of using the same are disclosed. An exemplary porous block nano-fiber composite (110) includes a porous block (100) having one or more pores (200). The porous block nano-fiber composite (110) also includes a plurality of inorganic nano-fibers (211) formed within at least one of the pores (200).

  20. Property Blocks: Games and Activities.

    Science.gov (United States)

    Humphreys, Alan, Ed.; Dailey, Jean, Ed.

    This pamphlet describes the property blocks produced by MINNEMAST, and discusses their use in the development of thinking processes. Classification systems, including block diagrams and tree diagrams, are discussed. Sixteen classroom activities and eleven games which use the blocks are described. Suggestions to the teacher for further reading are…

  1. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    Science.gov (United States)

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.

  2. Mechanisms of HIV persistence in HIV reservoirs.

    Science.gov (United States)

    Mzingwane, Mayibongwe L; Tiemessen, Caroline T

    2017-03-01

    The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half-life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut-associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low-level replication and persistent viremia during treatment. Latently, HIV-infected CD4+ T cells harboring replication-competent virus, HIV cell-to-cell spread, and HIV-infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Pregnancy and HIV

    Science.gov (United States)

    ... 17, 2014 Select a Language: Fact Sheet 611 Pregnancy and HIV HOW DO BABIES GET AIDS? HOW CAN WE ... doses due to nausea and vomiting during early pregnancy, giving HIV a chance to develop resistance The risk of ...

  4. HIV/AIDS Basics

    Science.gov (United States)

    ... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...

  5. Psychotropic prescribing in HIV

    African Journals Online (AJOL)

    2012-11-02

    Nov 2, 2012 ... multiple medications (ARVs, antibiotics, tuberculosis (TB) ... Psychiatric disorders frequently co-occur with HIV, as preceding conditions or consequent to HIV infection. ..... illness, substance abuse or personality disorder.

  6. Humanoid by ROBO-BLOCK

    Science.gov (United States)

    Niimi, Hirofumi; Koike, Minoru; Takeuchi, Seiichi; Douhara, Noriyoshi

    2007-12-01

    Humanoid by ROBO-BLOCK (robot block system) and the rational formula of robots were proposed. ROBO-BLOCK is composed of servo motors, the parts for servomotor rotor, the brackets for servomotor fixation, the board parts and the controllers. A robot can be assembled easily by ROBO-BLOCK. Meanwhile, it is convenient when the structure of the robot can be described easily as a character. The whole structure of the robot is expressed as rational formula of the robot to show molecule structure in chemistry. ROBO-BLOCK can be useful for not only the research but also the education. Creative student experiment was done in the college of industrial technology.

  7. 孕产妇艾滋病感染状况及母婴阻断的干预效果研究%Study on HIV Infection Prevalence of Pregnant and Lying - in Women and the Interventional Effects of Maternal - infant Transmission Blocking

    Institute of Scientific and Technical Information of China (English)

    肖丽华; 金海菊

    2011-01-01

    Objective To study the HIV infection prevalence in pregnant and lying - in women and the effects of prevention of mother-to-child transmission (PMTCT) in Lishui city, so as to provide proper intervention strategy. Methods HIV antibody test was performed in pregnant and lying - in women in Iishui city, and positive cases accepted further confirmatory testing. Results During 4 years of 2006 to 2010, 0.229‰ of those tested pregnant and lying - in women were detected and confirmed as HIV positive. The early detection of HIV during pregnancy can facilitate and strengthen the implementation of PMTCT. There were 7 infants over 18 months among all the 12 surviving infants bom by those HIV positive mothers. Among the 7 infants, 6 were detected as HIV negative and 1 declined the test. Conclusion The prevalence of HIV infection in pregnant and lying - in women in Iishui city is relatively low. Propaganda of HIV PMTCT should be strengthened, and integrated effectively with pre - marital, pre - conception and pregnancy health care. The detection rate of HIV infection before or during pregnancy should be improved to promote the health condition of pregnant and lying - in women and their infants.%目的 为了解丽水市孕产妇HIV感染状况及母婴阻断的干预效果,指导艾滋病母婴阻断工作.方法 对孕产妇进行HIV抗体检测,抗- HIV初筛阳性标本经艾滋病确认试验.结果 2006年10月1日—2010年9月30日4年间,孕产妇HIV感染率为2.29/万.孕期检出的HIV感染孕妇,更能配合母婴传播阻断措施的落实.目前存活的12名儿童有7名已满18个月,其中有6名抗- HIV抗体阴性,1名拒绝检测.结论 丽水市孕产妇HIV感染处于较低水平.今后应加强艾滋病母要阻断相关知识宣传,并将预防母婴传播服务与婚前、孕前、孕期保健有机结合,提高孕前和孕期HIV的检测率和HIV感染孕妇孕早期检出率.

  8. Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2.

    Directory of Open Access Journals (Sweden)

    Andrea Kinga Marias Furuya

    2016-04-01

    Full Text Available Marburg virus, the Kaposi's sarcoma-associated herpesvirus (KSHV and Dengue virus all activate, and benefit from, expression of the transcription regulator nuclear erythroid 2-related factor 2 (Nrf2. The impact of Nrf2 activation on human immunodeficiency virus (HIV infection has not been tested. Sulforaphane (SFN, produced in cruciferous vegetables after mechanical damage, mobilizes Nrf2 to potently reprogram cellular gene expression. Here we show for the first time that SFN blocks HIV infection in primary macrophages but not in primary T cells. Similarly SFN blocks infection in PMA-differentiated promonocytic cell lines, but not in other cell lines tested. siRNA-mediated depletion of Nrf2 boosted HIV infectivity in primary macrophages and reduced the anti-viral effects of SFN treatment. This supports a model in which anti-viral activity is mediated through Nrf2 after it is mobilized by SFN. We further found that, like the type I interferon-induced cellular anti-viral proteins SAMHD1 and MX2, SFN treatment blocks infection after entry, but before formation of 2-LTR circles. Interestingly however, neither SAMHD1 nor MX2 were upregulated. This shows for the first time that Nrf2 action can potently block HIV infection and highlights a novel way to trigger this inhibition.

  9. Hepatitis C and HIV

    Science.gov (United States)

    ... Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living with HIV in ... Notice Network blog.aids.gov • locator.aids.gov • HIV/AIDS Service Locator Locator Widgets • Instructions • API Find ...

  10. Hepatitis B and HIV

    Science.gov (United States)

    ... Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living with HIV in ... Notice Network blog.aids.gov • locator.aids.gov • HIV/AIDS Service Locator Locator Widgets • Instructions • API Find ...

  11. HIV Life Cycle

    Science.gov (United States)

    ... Content HIV Replication Cycle Antiretroviral Drug Discovery and Development Need Help? Call 1-800-448-0440 (1 p.m. to 4 p.m. ET) Send us an email The HIV Life Cycle Last Reviewed: August 18, 2017 Key Points HIV gradually destroys the immune system by attacking and killing a type of white ...

  12. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  13. Spintronics: Conceptual Building Blocks

    Science.gov (United States)

    Ansermet, J.-Ph.

    The purpose of this introduction to spintronics is to provide some elementary description of its conceptual building blocks. Thus, it is intended for a newcomer to the field. After recalling rudimentary descriptions of spin precession and spin relaxation, spin-dependent transport is treated within the Boltzmann formalism. This suffices to introduce key notions such as the spin asymmetry of the conductivities in the two-current model, the spin diffusion length, and spin accumulation. Two basic mechanisms of spin relaxation are then presented, one arising from spin-orbit scattering and the other from electron-magnon collisions. Finally, the action of a spin-polarized current on magnetization is presented in a thermodynamics framework. This introduces the notion of spin torque and the characteristic length scale over which the transverse spin polarization of conduction electron decays as it is injected into a magnet.

  14. Rotating ice blocks

    Science.gov (United States)

    Dorbolo, Stephane; Adami, Nicolas; Grasp Team

    2014-11-01

    The motion of ice discs released at the surface of a thermalized bath was investigated. As observed in some rare events in the Nature, the discs start spinning spontaneously. The motor of this motion is the cooling of the water close to the ice disc. As the density of water is maximum at 4°C, a downwards flow is generated from the surface of the ice block to the bottom. This flow generates the rotation of the disc. The speed of rotation depends on the mass of the ice disc and on the temperature of the bath. A model has been constructed to study the influence of the temperature of the bath. Finally, ice discs were put on a metallic plate. Again, a spontaneous rotation was observed. FNRS is thanked for financial support.

  15. Celiac ganglia block

    Energy Technology Data Exchange (ETDEWEB)

    Akinci, Devrim [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey); Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey)]. E-mail: oakhan@hacettepe.edu.tr

    2005-09-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation.

  16. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...... efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...

  17. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A

    2014-01-01

    The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  18. Restrictions to HIV-1 replication in resting CD4+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Pan; Hanna-Mari Baldauf; Oliver T Keppler; Oliver T Fackler

    2013-01-01

    CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV).In an activated state,CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals.In contrast,resting CD4+ T cells are highly resistant to productive HIV-1 infection,yet are massively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo.Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and,early after HIV-1entry,a block that limits reverse transcription of incoming viral RNA genomes.Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research.Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase,as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells.This review summarizes our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.

  19. The INSTI HIV-1/HIV-2 antibody test: a review.

    Science.gov (United States)

    Singh, Ameeta E; Lee, Bonita; Fenton, Jayne; Preiksaitis, Jutta

    2013-05-01

    Rapid HIV tests have been widely adopted globally as an important component of HIV prevention and control programs. The INSTI™ HIV-1/HIV-2 antibody test is a second-generation HIV antibody test, available in most countries for use from whole blood, serum, and plasma. Available data on kit characteristics and current performance data on the INSTI™ HIV-1/HIV-2 antibody test are presented together with six other rapid point-of-care tests (RPOCTs) for HIV antibody. Few published data are available providing direct comparisons of INSTI™ with other RPOCTs for HIV antibody and standard laboratory-based HIV-1/HIV-2 antibody assays. Existing data showed that INSTI™ has comparable performance to other RPOCTs but detected seroconversion later than standard laboratory-based assays. The good performance of INSTI HIV-1/HIV-2 antibody test, its ease of use, the rapid availability of results (resource-limited settings.

  20. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    Science.gov (United States)

    Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity. PMID:25378570

  1. Preintegration HIV-1 inhibition by a combination lentiviral vector containing a chimeric TRIM5 alpha protein, a CCR5 shRNA, and a TAR decoy.

    Science.gov (United States)

    Anderson, Joseph S; Javien, John; Nolta, Jan A; Bauer, Gerhard

    2009-12-01

    Human immunodeficiency virus (HIV) gene therapy offers a promising alternative approach to current antiretroviral treatments to inhibit HIV-1 infection. Various stages of the HIV life cycle including pre-entry, preintegration, and postintegration can be targeted by gene therapy to block viral infection and replication. By combining multiple highly potent anti-HIV transgenes in a single gene therapy vector, HIV-1 resistance can be achieved in transduced cells while prohibiting the generation of escape mutants. Here, we describe a combination lentiviral vector that encodes three highly effective anti-HIV genes functioning at separate stages of the viral life cycle including a CCR5 short hairpin RNA (shRNA) (pre-entry), a human/rhesus macaque chimeric TRIM5 alpha (postentry/preintegration), and a transactivation response element (TAR) decoy (postintegration). The major focus on designing this anti-HIV vector was to block productive infection of HIV-1 and to inhibit any formation of provirus that would maintain the viral reservoir. Upon viral challenge, potent preintegration inhibition of HIV-1 infection was achieved in combination vector-transduced cells in both cultured and primary CD34(+) hematopoietic progenitor cell (HPC)-derived macrophages. The generation of escape mutants was also blocked as evaluated by long-term culture of challenged cells. The ability of this combination anti-HIV lentiviral vector to prevent HIV-1 infection, in vitro, warrants further evaluation of its in vivo efficacy.

  2. Large Block Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W

    2001-12-01

    This report documents the Large-Block Test (LBT) conducted at Fran Ridge near Yucca Mountain, Nevada. The LBT was a thermal test conducted on an exposed block of middle non-lithophysal Topopah Spring tuff (Tptpmn) and was designed to assist in understanding the thermal-hydrological-mechanical-chemical (THMC) processes associated with heating and then cooling a partially saturated fractured rock mass. The LBT was unique in that it was a large (3 x 3 x 4.5 m) block with top and sides exposed. Because the block was exposed at the surface, boundary conditions on five of the six sides of the block were relatively well known and controlled, making this test both easier to model and easier to monitor. This report presents a detailed description of the test as well as analyses of the data and conclusions drawn from the test. The rock block that was tested during the LBT was exposed by excavation and removal of the surrounding rock. The block was characterized and instrumented, and the sides were sealed and insulated to inhibit moisture and heat loss. Temperature on the top of the block was also controlled. The block was heated for 13 months, during which time temperature, moisture distribution, and deformation were monitored. After the test was completed and the block cooled down, a series of boreholes were drilled, and one of the heater holes was over-cored to collect samples for post-test characterization of mineralogy and mechanical properties. Section 2 provides background on the test. Section 3 lists the test objectives and describes the block site, the site configuration, and measurements made during the test. Section 3 also presents a chronology of events associated with the LBT, characterization of the block, and the pre-heat analyses of the test. Section 4 describes the fracture network contained in the block. Section 5 describes the heating/cooling system used to control the temperature in the block and presents the thermal history of the block during the test

  3. Cyclic GMP-AMP Synthase is an Innate Immune Sensor of HIV and Other Retroviruses

    Science.gov (United States)

    Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J.

    2013-01-01

    Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic-GMP-AMP (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type-I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus (MLV) and Simian immunodeficiency virus (SIV). These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses. PMID:23929945

  4. Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  5. Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  6. Primaer HIV-infektion

    DEFF Research Database (Denmark)

    Pedersen, C; Pedersen, B K

    1996-01-01

    , oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove......Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely...... to be more sensitive, but are not yet used as routine methods. The course of the primary infection has prognostic importance for the subsequent course of HIV infection. This probably reflects the importance of both the viral phenotype and of the initial immune response to HIV. Primary HIV infection should...

  7. HIV and maternal mortality.

    Science.gov (United States)

    Lathrop, Eva; Jamieson, Denise J; Danel, Isabella

    2014-11-01

    The majority of the 17 million women globally that are estimated to be infected with HIV live in Sub-Saharan Africa. Worldwide, HIV-related causes contributed to 19 000-56 000 maternal deaths in 2011 (6%-20% of maternal deaths). HIV-infected pregnant women have two to 10 times the risk of dying during pregnancy and the postpartum period compared with uninfected pregnant women. Many of these deaths can be prevented with the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART. The paper summarizes what is known about HIV disease progression in pregnancy, specific causes of HIV-related maternal deaths, and the potential impact of treatment with antiretroviral therapy on maternal mortality. Recommendations are proposed for improving maternal health and decreasing maternal mortality among HIV-infected women based on existing evidence.

  8. Basic HIV/AIDS Statistics

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Statistics Center . How many people are diagnosed with HIV each year in the United States? In 2015, ...

  9. HIV Medicines and Side Effects

    Science.gov (United States)

    Side Effects of HIV Medicines HIV Medicines and Side Effects (Last updated 1/17/2017; last reviewed 1/17/2017) Key Points HIV medicines help people with ... will depend on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people ...

  10. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2016-01-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO(d+1,1) up into multiplets of SO(d,1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d-1 dimensions. In particular, we obtain a formula for 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  11. Reliability computation from reliability block diagrams

    Science.gov (United States)

    Chelson, P. O.; Eckstein, E. Y.

    1975-01-01

    Computer program computes system reliability for very general class of reliability block diagrams. Four factors are considered in calculating probability of system success: active block redundancy, standby block redundancy, partial redundancy, and presence of equivalent blocks in the diagram.

  12. HIV-2 neutralization by intact V3-specific Fab fragments

    Directory of Open Access Journals (Sweden)

    Sourial Samer

    2008-08-01

    Full Text Available Abstract The V3 region of both HIV-1 gp120 and HIV-2 gp125 surface glycoprotein has been described as a target for neutralizing antibodies. In this study a conformation-sensitive (3C4 and a linear site-specific (7C8 anti-HIV-2 V3 monoclonal antibody (mAb were characterized. The neutralization capacity of the purified mAbs and their respective papain-generated Fab fragments was analyzed. The Fabs were further characterized by sequence analysis. Our results demonstrate that neither purified mAbs were capable of neutralizing HIV-2, while intact Fab fragments from both mAbs blocked in vitro infection of HIV-2 isolates. Moreover, the conformation sensitive 3C4 Fab neutralized both subtype A and B HIV-2 isolates and SIVsm. Sequence analysis of the hypervariable regions of 3C4 Fab and 7C8 Fab revealed that the third CDR of the heavy chain (CDRH3 of the antibodies was not as long as many of the previously characterized neutralizing antibodies. Our findings suggest that whole 7C8 and 3C4 mAbs are sterically hindered from neutralizing HIV-2, whereas the smaller size of Fab fragments enables access to the V3 region on the virion surface.

  13. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo

    1997-05-01

    Full Text Available An ASQS(v is a particular Steiner system featuring a set of v vertices and two separate families of blocks, B and G, whose elements have a respective cardinality of 4 and 6. It has the property that any three vertices of X belong either to a B-block or to a G-block. The parameter cb is the number of common blocks in two separate ASQSs, both defined on the same set of vertices X . In this paper it is shown that cb ≤ 29 for any pair of ASQSs(12.

  14. Eikonalization of Conformal Blocks

    CERN Document Server

    Fitzpatrick, A Liam; Walters, Matthew T; Wang, Junpu

    2015-01-01

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the $t$-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the `eikonalization' of conformal blocks. We show that when an operator $T$ appears in the OPE $\\mathcal{O}(x) \\mathcal{O}(0)$, then the large spin $\\ell$ Fock space states $[TT \\cdots T]_{\\ell}$ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an $\\langle \\mathcal{O} \\mathcal{O} \\mathcal{O} \\mathcal{O} \\rangle$ correlator build the classical `$T$ field' in the dual AdS description. In some limits the sum of all Fock space exchanges can be represented as the exponential of a single $T$ exchange in the 4-pt correlator of $\\mathcal{O}$. Our results should be useful for systematizing $1/\\ell$ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading $\\log \\ell$...

  15. Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat.

    Science.gov (United States)

    Kafka, Jessica K; Sheth, Prameet M; Nazli, Aisha; Osborne, Brendan J; Kovacs, Colin; Kaul, Rupert; Kaushic, Charu

    2012-01-02

    Although more than 60% of HIV transmission occurs via semen, little is known about the immune impact of seminal plasma on HIV susceptibility. Here, we examined the level of selected immunomodulatory factors in seminal plasma from HIV-uninfected and therapy-naive, HIV-infected men in acute and chronic stages; the cytokine response elicited by seminal plasma in genital epithelial cells (GECs); and whether any GEC response to seminal plasma could drive HIV replication in infected T cells. A panel of nine cytokines and chemokines was measured in seminal plasma from HIV-uninfected and HIV-infected men and in primary GEC cultures following seminal plasma exposure. HIV-long terminal repeat (LTR) activation was measured in 1G5 T cells exposed to supernatants from seminal plasma-treated GECs. Pro-inflammatory cytokines and chemokines were present at significantly higher levels in seminal plasma from acute men, whereas transforming growth factor (TGF)-β1 was significantly higher in seminal plasma from chronic men. Pro-inflammatory cytokine production by GECs was significantly decreased following incubation with seminal plasma from chronic men. Blocking the TGF-β1 receptor in GECs prior to seminal plasma exposure enhanced pro-inflammatory cytokine production. Exposure to seminal plasma activated nuclear factor (NF)-κB in GECs and blocking it significantly reduced pro-inflammatory cytokine production. GEC responses to seminal plasma, especially from acute men, significantly activated HIV-LTR activation in 1G5 T cells. Immunomodulatory factors in seminal plasma vary, depending on presence and stage of HIV infection. Exposure to seminal plasma leads to NF-κB activation and pro-inflammatory cytokine production, whereas TGF-β in seminal plasma may suppress pro-inflammatory cytokine production by GECs. GEC responses to seminal plasma can activate HIV-LTR in infected CD4(+) T cells.

  16. HIV Testing in the United States

    Science.gov (United States)

    ... HIV/AIDS HIV Testing in the United States HIV Testing in the United States Jun 23, 2017 ... States or for refugees. 27 Insurance Coverage of HIV Testing HIV testing that is “medically necessary” – recommended ...

  17. What is a Preventive HIV Vaccine?

    Science.gov (United States)

    ... Therapeutic HIV Vaccine? What is a Preventive HIV Vaccine? HIV/AIDS Clinical Trials HIV Prevention The Basics of ... Send us an email What is a Preventive HIV Vaccine? Last Reviewed: August 16, 2017 Key Points A ...

  18. Adductor Canal Block versus Femoral Nerve Block and Quadriceps Strength

    DEFF Research Database (Denmark)

    Jæger, Pia Therese; Nielsen, Zbigniew Jerzy Koscielniak; Henningsen, Lene Marianne;

    2013-01-01

    : The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5-6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were...

  19. Prevalence of HIV associated neurocognitive deficit among HIV ...

    African Journals Online (AJOL)

    ... of HIV associated neurocognitive deficit among HIV positive people in Ethiopia: ... the factors associated with cognitive impairment among HIV positive people in ... activity of daily living scale and Hospital Anxiety and Depression scale were ...

  20. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available BACKGROUND: Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS. METHODS AND FINDINGS: This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP. CONCLUSION: This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  1. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    OpenAIRE

    Guanira, Juan V.; Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT r...

  2. HIV, AIDS, and the Future

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 ... turn Javascript on. Photo: The NAMES Project Foundation HIV and AIDS are a global catastrophe. While advances ...

  3. HIV/AIDS and Vaccines

    Science.gov (United States)

    ... against the disease. Is There a Vaccine for HIV? No. There is currently no vaccine that will ... in this video! /* // ** // */ Why Do We Need an HIV Vaccine? Today, more people living with HIV than ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... affect judgment and can lead to unsafe sexual practices, which put people at risk for getting HIV ...

  5. HIV/AIDS and Alcohol

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). Each year in the United States, between 55, ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction ...

  7. Living with HIV/AIDS

    Science.gov (United States)

    ... destroying the white blood cells that fight infection. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. Infection with HIV is serious. But thanks to ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... to help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency ... risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/AIDS and Drug Abuse: Intertwined Epidemics : Describes ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... access to the latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and the ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV infection in the United States. Drugs can change the way the brain works, disrupting the ... linked and referred to as "HIV/AIDS." HIV can be transferred between people if an infected person's ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is ... Atlanta, GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS ... but no cure, at the present time. The virus (HIV) and the disease it causes (AIDS) are ...

  15. Region 9 Census Block 2010

    Science.gov (United States)

    Geography:The TIGER Line Files are feature classes and related database files (.) that are an extract of selected geographic and cartographic information from the U.S. Census Bureau's Master Address File / Topologically Integrated Geographic Encoding and Referencing (MAF/TIGER) Database (MTDB). The MTDB represents a seamless national file with no overlaps or gaps between parts, however, each TIGER Line File is designed to stand alone as an independent data set, or they can be combined to cover the entire nation. Census Blocks are statistical areas bounded on all sides by visible features, such as streets, roads, streams, and railroad tracks, and/or by non visible boundaries such as city, town, township, and county limits, and short line-of-sight extensions of streets and roads. Census blocks are relatively small in area; for example, a block in a city bounded by streets. However, census blocks in remote areas are often large and irregular and may even be many square miles in area. A common misunderstanding is that data users think census blocks are used geographically to build all other census geographic areas, rather all other census geographic areas are updated and then used as the primary constraints, along with roads and water features, to delineate the tabulation blocks. As a result, all 2010 Census blocks nest within every other 2010 Census geographic area, so that Census Bureau statistical data can be tabulated at the block level and aggregated up t

  16. Block storage subsystem performance analysis

    CERN Document Server

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  17. The Effectiveness of Block Scheduling.

    Science.gov (United States)

    Creamean, Sharon Lightle; Horvath, Robert Jeffery

    This report describes a program for the exploration of block scheduling. The targeted population consists of high school students in a growing, middle-class community, located in a suburban setting of a large mid-western city. The historical background of block scheduling is documented through data gathered using attendance reports, student…

  18. Four-block beam collimator

    CERN Multimedia

    1977-01-01

    The photo shows a four-block collimator installed on a control table for positioning the alignment reference marks. Designed for use with the secondary beams, the collimators operated in vacuum conditions. The blocks were made of steel and had a standard length of 1 m. The maximum aperture had a square coss-section of 144 cm2. (See Annual Report 1976.)

  19. Block Transfer Agreement Evaluation Project

    Science.gov (United States)

    Bastedo, Helena

    2010-01-01

    The objective of this project is to evaluate for the British Columbia Council on Admissions and Transfer (BCCAT) the effectiveness of block transfer agreements (BTAs) in the BC Transfer System and recommend steps to be taken to improve their effectiveness. Findings of this study revealed that institutions want to expand block credit transfer;…

  20. OPAL Various Lead Glass Blocks

    CERN Multimedia

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  1. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...

  2. Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

    Directory of Open Access Journals (Sweden)

    Song Xinming

    2009-08-01

    Full Text Available Abstract Background Highly active anti-retroviral therapy (HAART is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication. Methods Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc was used to identify potential anti-HIV mechanisms of these extracts. Results Two extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE and one from Dipterocarpaceae, Vatica astrotricha (VAD inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus. Conclusion These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking

  3. HIV testing in Switzerland.

    Science.gov (United States)

    Jeannin, A; Dubois-Arber, F; Paccaud, F

    1994-11-01

    To obtain information about the prevalence of, reasons for, and adequacy of HIV testing in the general population in Switzerland in 1992. Telephone survey (n = 2800). Some 47% of the sample underwent one HIV test performed through blood donation (24%), voluntary testing (17%) or both (6%). Of the sample, 46% considered themselves well or very well informed about the HIV test. Patients reported unsystematic pre-test screening by doctors for the main HIV risks. People having been in situations of potential exposure to risk were more likely to have had the test than others. Overall, 85% of those HIV-tested had a relevant, generally risk-related reason for having it performed. HIV testing is widespread in Switzerland. Testing is mostly performed for relevant reasons. Pre-test counselling is poor and an opportunity for prevention is thus lost.

  4. Drug-induced reactivation of apoptosis abrogates HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Hartmut M Hanauske-Abel

    Full Text Available HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of

  5. Acquisition of HIV-1 resistance in T lymphocytes using an ACA-specific E. coli mRNA interferase.

    Science.gov (United States)

    Chono, Hideto; Matsumoto, Kazuya; Tsuda, Hiroshi; Saito, Naoki; Lee, Karim; Kim, Sujeong; Shibata, Hiroaki; Ageyama, Naohide; Terao, Keiji; Yasutomi, Yasuhiro; Mineno, Junichi; Kim, Sunyoung; Inouye, Masayori; Kato, Ikunoshin

    2011-01-01

    Transcriptional activation of gene expression directed by the long terminal repeat (LTR) of HIV-1 requires both the transactivation response element (TAR) and Tat protein. HIV-1 mutants lacking a functional tat gene are not able to proliferate. Here we take a genetic approach to suppress HIV-1 replication based on Tat-dependent production of MazF, an ACA-specific endoribonuclease (mRNA interferase) from Escherichia coli. When induced, MazF is known to cause Bak- and NBK-dependent apoptotic cell death in mammalian cells. We first constructed a retroviral vector, in which the mazF (ACA-less) gene was inserted under the control of the HIV-1 LTR, which was then transduced into CD4+ T-lymphoid CEM-SS cells in such a way that, upon HIV-1 infection, the mazF gene is induced to destroy the infecting HIV-1 mRNA, preventing HIV-1 replication. Indeed, when the transduced cells were infected with HIV-1 IIIB, the viral replication was effectively inhibited, as HIV-1 IIIB p24 could not be detected in the culture medium. Consistently, not only cell growth but also the CD4 level was not affected by the infection. These results suggest that the HIV-1-LTR-regulated mazF gene was effectively induced upon HIV-1 IIIB infection, which is sufficient enough to destroy the viral mRNA from the infected HIV-1 IIIB to completely block viral proliferation in the cells, but not to affect normal cell growth. These results indicate that the T cells transduced with the HIV-1-LTR-regulated mazF gene acquire HIV-1 resistance, providing an intriguing potential for the use of the HIV-1-LTR-regulated mazF gene in anti-HIV gene therapy.

  6. HIV/AIDS eradication

    OpenAIRE

    Marsden, Matthew D.; Zack, Jerome A.

    2013-01-01

    Antiretroviral therapy can inhibit HIV replication in patients and prevent progression to AIDS. However, it is not curative. Here we provide an overview of what antiretroviral drugs do and how the virus persists during therapy in rare reservoirs, such as latently infected CD4+ T cells. We also outline several innovative methods that are currently under development to eradicate HIV from infected individuals. These strategies include gene therapy approaches intended to create an HIV-resistant i...

  7. Science challenging HIV infection.

    Science.gov (United States)

    Rao, R R; Lakshi, V

    1993-04-01

    The first accepted report of a novel human, slow virus disease belonging to "lentivirus" known as acquired immunodeficiency syndrome can be traced to reports of June 1981. HIV-1 and HIV-2 were later found over the period 1984-86 to be unequivocally associated with AIDS. They are two serologically distinct viruses belonging to the same family with the unique properties of integration and latency in the host cell genome and the presence of reverse transcriptase. Typical of all retroviruses, the HIV genome comprises three genes governing the synthesis of all core proteins, replication protein encoding, and envelope proteins. HIV uses the CD4 antigen on T-helper cells, and about 40% of blood monocytes and tissue macrophages as a cell surface receptor. HIV may, however, also infect cells which contain no CD4. Macrophages serve as the main reservoir of HIV and may carry the virus to different organs. Very recently a rare type of white blood cell called the dendritic cell has been found to allow for direct infection by HIV during sexual intercourse. These cells are prominently present in the anal and vaginal mucosa. The authors discuss facts and figures on the HIV epidemic, the Indian scenario, classification of the clinical spectrum, the enzyme immunoassay HIV testing format, Western blot, immunofluorescence antibody, HIV culture, flow cytometry, radio immuno precipitation assay, and the detection of HIV DNA. Significant advances have been made over the last ten years in understanding the pathogenesis of HIV infection and accurately diagnosing infected individuals, with recombinant technology, polymerase chain reaction, and the construction of synthetic hybrid virus rapidly becoming part of routine diagnostics. More sensitive, specific, and rapid techniques are, however, needed for the early diagnosis and management of AIDS cases. The need for more ideal antibody incorporating both regulatory and structural proteins of the virion, preferably manufactured using

  8. CCR5 inhibitors: Emerging promising HIV therapeutic strategy

    Directory of Open Access Journals (Sweden)

    Surya Rao Padmasri

    2009-01-01

    Full Text Available Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result, better effective, safe antiretroviral drugs and treatment strategies keep on to be pursued. In this process, CCR5 (chemokine receptor 5 inhibitors are a new class of antiretroviral drug used in the treatment of HIV. They are designed to prevent HIV infection of CD4 T-cells by blocking the CCR5. When the CCR5 receptor is unavailable, ′R5-tropic′ HIV (the variant of the virus that is common in earlier HIV infection cannot engage with a CD4 T-cell to infect the cell. In August 2007, the FDA approved the first chemokine (C-C motif CCR5 inhibitor, maraviroc, for treatment-experienced patients infected with R5-using virus. Studies from different cohort in regions, affected by clad B HIV-1, demonstrate that 81-88% of HIV-1 variants in treatment naïve patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed tropic i.e., are able to utilize both CCR5 and CXCR4 coreceptors. In treatment experienced patients, 49−78% of the variants are purely CCR5 tropic, 22−48% are dual/mixed tropic, and 2-5% exclusively utilize CXCR4. A 32 bp deletion in the CCR5 gene, which results in a frame shift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5 tropic HIV-1 virus. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, and African ethnic groups. HIV-infected individuals, who are heterozygous for CCR5 delta 32, have slower rates of disease progression. The currently available data supports the continuation of the development of CCR5 antagonists in different settings related

  9. Initiation of HIV therapy

    OpenAIRE

    Ho, Charlotte Yuk-Fan; Ling, Bingo Wing-Kuen

    2010-01-01

    In this paper, we numerically show that the dynamics of the HIV system is sensitive to both the initial condition and the system parameters. These phenomena imply that the system is chaotic and exhibits a bifurcation behavior. To control the system, we propose to initiate an HIV therapy based on both the concentration of the HIV-1 viral load and the ratio of the CD4 lymphocyte population to the CD8 lymphocyte population. If the concentration of the HIV-1 viral load is higher than a threshold,...

  10. Unrecognised HIV related deaths.

    OpenAIRE

    McCormick, A.

    1991-01-01

    OBJECTIVES--To establish whether follow up of deaths from selected HIV related causes could increase the number of cases of HIV infection reported to the Public Health Laboratory Service Communicable Disease Surveillance Centre (CDSC), and to estimate the proportion of deaths among HIV positive men that occurred in men who were not known to be HIV positive at the time of death by the person who signed the death certificate. DESIGN--Follow up of draft death entries received by the Office of Po...

  11. Treatment for HIV

    Science.gov (United States)

    ... Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home Guidelines Integrated ...

  12. Drugs, Alcohol and HIV

    Science.gov (United States)

    ... Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home Guidelines Integrated ...

  13. Mental Health and HIV

    Science.gov (United States)

    ... Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home Guidelines Integrated ...

  14. Language and HIV communication

    Directory of Open Access Journals (Sweden)

    Lynn VA

    2017-09-01

    Full Text Available Vickie A LynnDepartment of Community and Family Health, College of Public Health, University of South Florida, Tampa, FL, USAI am writing to comment on Kontomanolis et al’s recent article entitled “The social stigma of HIV-AIDS: society’s role”.1 Although I applaud the authors for writing about this important topic and I wholeheartedly agree that HIV-related stigma is devastating to women living with HIV, I want to point out that using stigmatizing language when writing an article about HIV-related stigma is counterproductive.View the original paper by Kontomanolis and colleagues.

  15. Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.

    Directory of Open Access Journals (Sweden)

    Ruizhong Shen

    Full Text Available Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT. Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

  16. N-terminal Slit2 inhibits HIV-1 replication by regulating the actin cytoskeleton

    Directory of Open Access Journals (Sweden)

    Anand Appakkudal R

    2013-01-01

    Full Text Available Abstract Background Slit2 is a ~ 200 kDa secreted glycoprotein that has been recently shown to regulate immune functions. However, not much is known about its role in HIV (human immunodeficiency virus-1 pathogenesis. Results In the present study, we have shown that the N-terminal fragment of Slit2 (Slit2N (~120 kDa inhibits replication of both CXCR4 and CCR5-tropic HIV-1 viruses in T-cell lines and peripheral blood T-cells. Furthermore, we demonstrated inhibition of HIV-1 infection in resting CD4+ T-cells. In addition, we showed that Slit2N blocks cell-to-cell transmission of HIV-1. We have shown that Slit2N inhibits HIV-1 infection by blocking viral entry into T-cells. We also ruled out Slit2N-mediated inhibition of various other steps in the life cycle including binding, integration and viral transcription. Elucidation of the molecular mechanism revealed that Slit2N mediates its functional effects by binding to Robo1 receptor. Furthermore, we found that Slit2N inhibited Gp120-induced Robo1-actin association suggesting that Slit2N may inhibit cytoskeletal rearrangements facilitating HIV-1 entry. Studies into the mechanism of inhibition of HIV-1 revealed that Slit2N abrogated HIV-1 envelope-induced actin cytoskeletal dynamics in both T-cell lines and primary T-cells. We further showed that Slit2N specifically attenuated the HIV-1 envelope-induced signaling pathway consisting of Rac1, LIMK and cofilin that regulates actin polymerization. Conclusions Taken together, our results show that Slit2N inhibits HIV-1 replication through novel mechanisms involving modulation of cytoskeletal dynamics. Our study, thus, provides insights into the role of Slit2N in HIV-1 infection and underscores its potential in limiting viral replication in T-cells.

  17. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-03-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  18. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  19. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  20. Slow progress against HIV.

    Science.gov (United States)

    Alcorn, K

    1995-01-01

    Treatment for people with HIV attempts to prevent HIV from reproducing, boost the immune system, or cure opportunistic infections. The chemical structure of anti-viral drugs is similar to that of DNA. Since HIV bonds with the drugs rather than DNA, it cannot replicate itself. The most widely used anti-viral drug is zidovudine or AZT (brand name, Retrovir), but it does not help HIV infected persons who are still healthy. A recent trial shows that a combination of anti-viral drugs is more likely to delay opportunistic infections and death than AZT alone. When pregnant women use AZT before and during delivery and when their newborns receive AZT therapy, the likelihood of HIV transmission to the newborn is reduced by about 66%. Follow-up studies are needed, however, since AZT is toxic. Disadvantages of anti-viral drugs include resistance, toxicity, side effects (e.g., nausea and anemia), which are particularly severe at high doses, and accessibility of regular and expensive monitoring tests. Protease inhibitors are in the early stages of development. They deactivate the HIV enzyme which allows HIV to attach to white blood cells. Imuthiol (DTC) aims to increase the number of white blood cells so the body can fight HIV longer, but it appears that it has no benefit and may even facilitate development of opportunistic infections. Interleuken 2 may increase the number of CD4 cells. Alternative approaches to strengthening the immune system are lifestyle changes, improved diet, reduced stress, Chinese medicine and acupuncture, herbal medicines, and relaxation exercises. HIV/AIDS therapies are very expensive and often induce side effects. Many HIV positive people in developed countries are opting out of these treatments, even though they have access to them. Prevention and treatment of opportunistic infection remain the best strategies for most HIV-infected persons.

  1. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  2. Hawaii Census 2000 Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data layer represents Census 2000 demographic data derived from the PL94-171 redistricting files and SF3. Census geographic entities include blocks, blockgroups...

  3. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter;

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  4. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  5. MarineMineralsProgramBlocks

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains OCS block outlines and delineated polygons in ESRI ArcGIS shape file format for the BOEM Gulf of Mexico Region that contain sediment resources...

  6. The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.

    Directory of Open Access Journals (Sweden)

    Robin G Mansour

    Full Text Available Tenascin-C (TNC is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals.

  7. The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.

    Science.gov (United States)

    Mansour, Robin G; Stamper, Lisa; Jaeger, Frederick; McGuire, Erin; Fouda, Genevieve; Amos, Joshua; Barbas, Kimberly; Ohashi, Tomoo; Alam, S Munir; Erickson, Harold; Permar, Sallie R

    2016-01-01

    Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals.

  8. Multi-block and path modelling procedures

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    2008-01-01

    The author has developed a unified theory of path and multi-block modelling of data. The data blocks are arranged in a directional path. Each data block can lead to one or more data blocks. It is assumed that there is given a collection of input data blocks. Each of them is supposed to describe one...

  9. FAITH – Fast Assembly Inhibitor Test for HIV

    Energy Technology Data Exchange (ETDEWEB)

    Hadravová, Romana [Institute of Organic Chemistry and Biochemistry IOCB Research Centre & Gilead Sciences, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague (Czech Republic); Rumlová, Michaela, E-mail: michaela.rumlova@vscht.cz [Institute of Organic Chemistry and Biochemistry IOCB Research Centre & Gilead Sciences, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague (Czech Republic); Department of Biotechnology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague (Czech Republic); Ruml, Tomáš, E-mail: tomas.ruml@vscht.cz [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, 166 28 Prague (Czech Republic)

    2015-12-15

    Due to the high number of drug-resistant HIV-1 mutants generated by highly active antiretroviral therapy (HAART), there is continuing demand for new types of inhibitors. Both the assembly of the Gag polyprotein into immature and mature HIV-1 particles are attractive candidates for the blocking of the retroviral life cycle. Currently, no therapeutically-used assembly inhibitor is available. One possible explanation is the lack of a reliable and simple assembly inhibitor screening method. To identify compounds potentially inhibiting the formation of both types of HIV-1 particles, we developed a new fluorescent high-throughput screening assay. This assay is based on the quantification of the assembly efficiency in vitro in a 96-well plate format. The key components of the assay are HIV-1 Gag-derived proteins and a dual-labelled oligonucleotide, which emits fluorescence only when the assembly of retroviral particles is inhibited. The method was validated using three (CAI, BM2, PF74) reported assembly inhibitors. - Highlights: • Allows screening of assembly inhibitors of both mature and immature HIV-1 particles. • Based on Gag-derived proteins with CA in mature or immature conformation. • Simple and sensitive method suitable for high-throughput screening of inhibitors. • Unlike in other HIV assembly methods, works under physiological conditions. • No washing steps are necessary.

  10. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  11. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  12. HIV-1, human interaction database: current status and new features.

    Science.gov (United States)

    Ako-Adjei, Danso; Fu, William; Wallin, Craig; Katz, Kenneth S; Song, Guangfeng; Darji, Dakshesh; Brister, J Rodney; Ptak, Roger G; Pruitt, Kim D

    2015-01-01

    The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database', available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein-human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12,786 protein-protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14,102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set.

  13. Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    for pseudotypes to escape neutralization by the immune system in vivo. Previous reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  14. A Novel Tetrathiafulvalene Building Block

    DEFF Research Database (Denmark)

    Jeppesen, Jan Oskar; Takimiya, Kazuo; Thorup, Niels

    1999-01-01

    Efficient synthesis of a novel tetrathiafulvalene building block. 2,3-bis(2-cyanoethylthio)-6,7-bis(thiocyanato-methyl)tetrathiafulv alene (7) useful for stepwise and asymmetrical bis-function-alization is reported.......Efficient synthesis of a novel tetrathiafulvalene building block. 2,3-bis(2-cyanoethylthio)-6,7-bis(thiocyanato-methyl)tetrathiafulv alene (7) useful for stepwise and asymmetrical bis-function-alization is reported....

  15. [Superior gluteal nerve: a new block on the block?

    Science.gov (United States)

    Sá, Miguel; Graça, Rita; Reis, Hugo; Cardoso, José Miguel; Sampaio, José; Pinheiro, Célia; Machado, Duarte

    2017-05-24

    The superior gluteal nerve is responsible for innervating the gluteus medius, gluteus minimus and tensor fascia latae muscles, all of which can be injured during surgical procedures. We describe an ultrasound-guided approach to block the superior gluteal nerve which allowed us to provide efficient analgesia and anesthesia for two orthopedic procedures, in a patient who had significant risk factors for neuraxial techniques and deep peripheral nerve blocks. An 84-year-old female whose regular use of clopidogrel contraindicated neuraxial techniques or deep peripheral nerve blocks presented for urgent bipolar hemiarthroplasty in our hospital. Taking into consideration the surgical approach chosen by the orthopedic team, we set to use a combination of general anesthesia and superficial peripheral nerve blocks (femoral, lateral cutaneous of thigh and superior gluteal nerve) for the procedure. A month and a half post-discharge the patient was re-admitted for debriding and correction of suture dehiscence; we performed the same blocks and light sedation. She remained comfortable in both cases, and reported no pain in the post-operative period. Deep understanding of anatomy and innervation empowers anesthesiologists to solve potentially complex cases with safer, albeit creative, approaches. The relevance of this block in this case arises from its innervation of the gluteus medius muscle and posterolateral portion of the hip joint. To the best of our knowledge, this is the first report of an ultrasound-guided superior gluteal nerve block with an analgesic and anesthetic goal, which was successfully achieved. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. NANOSTRUCTURES OF FUNCTIONAL BLOCK COPOLYMERS

    Institute of Scientific and Technical Information of China (English)

    Guojun Liu

    2000-01-01

    Nanostructure fabrication from block copolymers in my group normally involves polymer design, synthesis, selfassembly, selective domain crosslinking, and sometimes selective domain removal. Preparation of thin films with nanochannels was used to illustrate the strategy we took. In this particular case, a linear triblock copolymer polyisopreneblock-poly(2-cinnamoylethyl methacrylate)-block-poly(t-butyl acrylate), PI-b-PCEMA-b-PtBA, was used. Films, 25 to50μm thick, were prepared from casting on glass slides a toluene solution of PI-b-PCEMA-b-PtBA and PtBA homopolymer,hPtBA, where hPtBA is shorter than the PtBA block. At the hPtBA mass fraction of 20% relative to the triblock or the total PtBA (hPtBA and PtBA block) volume fraction of 0.44, hPtBA and PtBA formed a seemingly continuous phase in the matrix of PCEMA and PI. Such a block segregation pattern was locked in by photocrosslinking the PCEMA domain. Nanochannels were formed by extracting out hPtBA with solvent. Alternatively, larger channels were obtained from extracting out hPtBA and hydrolyzing the t-butyl groups of the PtBA block. Such membranes were not liquid permeable but had gas permeability constants ~6 orders of magnitude higher than that of low-density polyethylene films.

  17. HIV-1 transcriptional regulation in the central nervous system and implications for HIV cure research

    Science.gov (United States)

    Churchill, Melissa J.; Cowley, Daniel J.; Wesselingh, Steve L.; Gorry, Paul R.; Gray, Lachlan R.

    2014-01-01

    Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system (CNS) during acute infection which can result in HIV-associated neurocognitive disorders (HAND) in up to 50% of patients, even in the presence of combination antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs in the perivascular macrophages and microglia. Astrocytes also become infected, although their infection is restricted and does not give rise to new viral particles. The major barrier to the elimination of HIV-1 is the establishment of viral reservoirs in different anatomical sites throughout the body and viral persistence during long-term treatment with cART. While the predominant viral reservoir is believed to be resting CD4+ T-cells in the blood, other anatomical compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and genital tract can also harbor persistently infected cellular reservoirs of HIV-1. Viral latency is predominantly responsible for HIV-1 persistence, and is most likely governed at the transcriptional level. Current clinical trials are testing transcriptional activators, in the background of cART, in an attempt to purge these viral reservoirs and reverse viral latency. These strategies aim to activate viral transcription in cells constituting the viral reservoir, so they can be recognized and cleared by the immune system, while new rounds of infection are blocked by co-administration of cART. The CNS has several unique characteristics that may result in differences in viral transcription and in the way latency is established. These include CNS-specific cell types, different transcription factors, altered immune surveillance, and reduced antiretroviral drug bioavailability. A comprehensive understanding of viral transcription and latency in the CNS is required in order to determine treatment outcomes when using transcriptional activators within the CNS. PMID:25060300

  18. Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion

    Directory of Open Access Journals (Sweden)

    de la Vega Michelle

    2011-12-01

    Full Text Available Abstract Background We recently provided evidence that HIV-1 enters HeLa-derived TZM-bl and lymphoid CEMss cells by fusing with endosomes, whereas its fusion with the plasma membrane does not proceed beyond the lipid mixing step. The mechanism of restriction of HIV-1 fusion at the cell surface and/or the factors that aid the virus entry from endosomes remain unclear. Results We examined HIV-1 fusion with a panel of target cells lines and with primary CD4+ T cells. Kinetic measurements of fusion combined with time-resolved imaging of single viruses further reinforced the notion that HIV-1 enters the cells via endocytosis and fusion with endosomes. Furthermore, we attempted to deliberately redirect virus fusion to the plasma membrane, using two experimental strategies. First, the fusion reaction was synchronized by pre-incubating the viruses with cells at reduced temperature to allow CD4 and coreceptors engagement, but not the virus uptake or fusion. Subsequent shift to a physiological temperature triggered accelerated virus uptake followed by entry from endosomes, but did not permit fusion at the cell surface. Second, blocking HIV-1 endocytosis by a small-molecule dynamin inhibitor, dynasore, resulted in transfer of viral lipids to the plasma membrane without any detectable release of the viral content into the cytosol. We also found that a higher concentration of dynasore is required to block the HIV-endosome fusion compared to virus internalization. Conclusions Our results further support the notion that HIV-1 enters disparate cell types through fusion with endosomes. The block of HIV-1 fusion with the plasma membrane at a post-lipid mixing stage shows that this membrane is not conducive to fusion pore formation and/or enlargement. The ability of dynasore to interfere with the virus-endosome fusion suggests that dynamin could be involved in two distinct steps of HIV-1 entry - endocytosis and fusion within intracellular compartments.

  19. APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study.

    Directory of Open Access Journals (Sweden)

    Iraj Hosseini

    Full Text Available The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the virus and prevent or decrease symptoms of illness. To learn about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, National Center for HIV, STD, ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that ... AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people if an ...

  2. FDA-Approved HIV Medicines

    Science.gov (United States)

    HIV Treatment FDA-Approved HIV Medicines (Last updated 2/27/2017; last reviewed 2/27/2017) Treatment with HIV medicines is ... approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in the ...

  3. HIV: Treatment and Comorbidity

    NARCIS (Netherlands)

    C. Rokx (Casper)

    2016-01-01

    markdownabstractClinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient s

  4. HIV-1 envelope glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Caulfield, Michael; Cupo, Albert; Dean, Hansi; Hoffenberg, Simon; King, C. Richter; Klasse, P. J.; Marozsan, Andre; Moore, John P.; Sanders, Rogier W.; Ward, Andrew; Wilson, Ian; Julien, Jean-Philippe

    2017-08-22

    The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

  5. Travelling with HIV

    DEFF Research Database (Denmark)

    Nielsen, Ulla S; Jensen-Fangel, Søren; Pedersen, Gitte

    2013-01-01

    We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals.......We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals....

  6. HIV and AIDS

    Science.gov (United States)

    ... one HIV test by the time they are teens. If you are having sex, have had sex in the past, or shared ... reviewed: October 2015 previous 1 • 2 • ... STDs How Do People Get AIDS? Can You Get HIV From Having Sex With Someone Who Has AIDS? Can Someone Get ...

  7. Let's Stop HIV Together

    Centers for Disease Control (CDC) Podcasts

    2012-07-16

    This podcast features 22 individuals who encourage others in the fight against HIV.  Created: 7/16/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 7/16/2012.

  8. Hepatitis A and HIV

    Science.gov (United States)

    ... Hepatitis B and Hepatitis C . Hepatitis A and HIV Hepatitis A is preventable with a vaccine, and ... Notice Network blog.aids.gov • locator.aids.gov • HIV/AIDS Service Locator Locator Widgets • Instructions • API Find ...

  9. Ludacris Talks About HIV

    Centers for Disease Control (CDC) Podcasts

    2012-07-24

    Ludacris, award winning singer and actor, urges everyone to talk about HIV/AIDS and its prevention.  Created: 7/24/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 7/24/2012.

  10. HIV/AIDS - resources

    Science.gov (United States)

    Resources - HIV/AIDS ... information on AIDS : AIDS.gov -- www.aids.gov AIDS Info -- aidsinfo.nih.gov The Henry J. Kaiser Family Foundation -- www.kff.org/hivaids US Centers for Disease Control and Prevention -- www.cdc.gov/hiv

  11. HIV and Communication

    Science.gov (United States)

    McNeilly, L.G.

    2005-01-01

    The human immunodeficiency virus (HIV) continues to plague many countries across the globe, including the United States, Africa, China and India. Children and adults have been infected with HIV, and both populations can present with communication disorders that coexist with the presence of the virus. The purpose of this paper is to present an…

  12. HIV and Viral Hepatitis

    Science.gov (United States)

    ... HAV for people who are at risk for HIV infection, including MSM; users of recreational drugs, whether injected or not; and sex partners of infected people. • • HBV: The best way to prevent HBV ... have or are at risk for HIV infection, including MSM; people who inject drugs; sex ...

  13. HIV/AIDS

    Science.gov (United States)

    ... People who are infected with HIV sometimes try dietary supplements that claim to boost the immune system or counteract side effects of anti-HIV drugs. Supplements that may be helpful Acetyl-L-carnitine. Researchers have used acetyl-L-carnitine to treat ...

  14. Psychoneuroimmunology and HIV-1.

    Science.gov (United States)

    Antoni, Michael H.; And Others

    1990-01-01

    Presents evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high risk human immunodeficiency virus-Type 1 (HIV-1) seronegative and very early stage seropositive homosexual men. HIV-1 infection is cast as chronic disease for which early…

  15. HIV-Positive-to-HIV-Positive Liver Transplantation

    OpenAIRE

    Calmy, Alexandra; van Delden, Christian; Giostra, Emiliano; Junet, C; Rubbia Brandt, L; Yerly, S; Chave, J-P; Samer, Caroline Flora; Elkrief, Laure; Vionnet, J; Berney, Thierry

    2016-01-01

    Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidr...

  16. Epitope Mapping of Ibalizumab, a Humanized Anti-CD4 Monoclonal Antibody with Anti-HIV-1 Activity in Infected Patients▿

    OpenAIRE

    Song, Ruijiang; Franco, David; Kao, Chia-Ying; Yu, Faye; Huang, Yaoxing; Ho, David D.

    2010-01-01

    Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1). With its unique specificity for domain 2 of CD4, this antibody potently and broadly blocks HIV-1 infection in vitro by inhibiting a postbinding step required for viral entry but without interfering with major histocompatibility complex class II (MHC-II)-mediated immune function. In clinical trials, ibalizumab has demonstrated anti-HIV-1 activity in patients...

  17. Cell-specific RNA aptamer against human CCR5 specifically targets HIV-1 susceptible cells and inhibits HIV-1 infectivity.

    Science.gov (United States)

    Zhou, Jiehua; Satheesan, Sangeetha; Li, Haitang; Weinberg, Marc S; Morris, Kevin V; Burnett, John C; Rossi, John J

    2015-03-19

    The C-C chemokine receptor type 5 (CCR5) is a receptor expressed by T cells and macrophages that serves as a coreceptor for macrophage-tropic HIV-1. Loss of CCR5 is associated with resistance to HIV-1. Here, we combine the live-cell-based SELEX with high-throughput sequencing technology to generate CCR5 RNA aptamers capable of specifically targeting HIV-1 susceptible cells (as small interfering RNA [siRNA] delivery agent) and inhibiting HIV-1 infectivity (as antiviral agent) via block of the CCR5 required for HIV-1 to enter cells. One of the best candidates, G-3, efficiently bound and was internalized into human CCR5-expressing cells. The G-3 specifically neutralized R5 virus infection in primary peripheral blood mononuclear cells, and in vivo generated human CD4(+) T cells with a nanomolar inhibitory concentration 50%. G-3 was also capable of transferring functional siRNAs to CCR5-expressing cells. Collectively, the cell-specific, internalizing, CCR5-targeted aptamers and aptamer-siRNA conjugates offer promise for overcoming some of the current challenges of drug resistance in HIV-1 by providing cell-type- or tissue-specific delivery of various therapeutic moieties.

  18. HIV-1 transmission during early antiretroviral therapy: evaluation of two HIV-1 transmission events in the HPTN 052 prevention study.

    Directory of Open Access Journals (Sweden)

    Li-Hua Ping

    Full Text Available In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART. We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.

  19. HIV-1/AIDS vaccine development: are we in the darkness before the dawn?

    Institute of Scientific and Technical Information of China (English)

    QIU Chao; XU Jian-qing

    2008-01-01

    @@ The pandemic of human immunodeficiency virus type 1 (HIV-1) has been devastating for the last two decades in a number of developing countries and constituting a grand challenge to the public health.WHO/UNAIDS estimates that approximately 33.2million people were living with HIV-1 infection by the end of 2007 and almost 2.5 million new infections occurred in 2007. An unprecedented scientifc challenge for the AIDS vaccine community is how to develop an effective HIV vaccine that can block HIV transmission and consequently stop the continuing spread of HIV-1.The recent failure of Merck Phase Ⅱ B trial alerted the HIV vaccine community that new vaccine strategies need to be more exclusively explored. In this review, we outline the basics of HIV vaccine and retrospect the history of the road to HIV vaccine in last two decades,and highlight the challenges we are currently facing and new strategies to develop HIV vaccines in this field.The Institute of Biomedical Sciences, Fudan University, Shanghai

  20. Indikatorsygdomme for hiv-infektion

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Andersen, Åse Bengård; Koch, Anders

    2015-01-01

    The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published...... a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection....

  1. HIV Vaccination, is Breakthrough Underway?

    Science.gov (United States)

    Lu, Da-Yong; Wu, Hong-Ying; Lu, Ting-Ren; Xu, Bin; Ding, Jian

    2016-01-01

    After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis.

  2. Nutrition and HIV

    DEFF Research Database (Denmark)

    Friis, Henrik; Olsen, Mette Frahm; Filteau, Suzanne

    2017-01-01

    The impact of the global human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic is most severe in sub-Saharan African countries already affected by undernutrition and food insecurity. There is a two-way relationship between HIV and undernutrition and food insecurity......, which is mainly synergistic and operating at different levels. HIV infection increases energy and nutrient requirements, yet it reduces food security. The result is nutritional deficiencies, which increase progression of HIV infection. Both undernutrition and food insecurity may also lead to increased...... risk of transmission. Nutritional intake and status may affect metabolism of antiretroviral drugs, some of which may affect body composition, and increase risk of the metabolic syndrome. In addition, HIV is transmitted through breastfeeding, causing a serious infant feeding dilemma for which...

  3. Cutaneous Leishmaniasis with HIV.

    Science.gov (United States)

    Talat, Humaira; Attarwala, Sharmeen; Saleem, Mubasshir

    2014-05-01

    Cutaneous Leishmaniasis (CL) is a vector borne disease caused by various species of the Leishmania parasite. CL is endemic in the province of Balochistan in Pakistan. In certain instances a Human Immunodeficiency Virus (HIV)-related immunocompromised is associated with atypical clinical presentation and occurrence of reactivated lesions of CL. Such presentations respond poorly to the standard treatment and frequent relapses are noted. We are reporting three cases of localized and disseminated CL due to Leishmania tropica which responded to meglumine antimoniate. Due to the fact that CL is endemic in Balochistan, we did not consider HIV infection as a causative organism. It was their presentation with history of weight loss and fever that prompted Enzyme-linked Immunosorbent Assay (ELISA) tests for HIV, which turned out to be positive. CL is becoming visible as an opportunistic infection associated with HIV/AIDS and may even be the first symptom in HIV positive patients in an endemic area.

  4. HIV-Associated Tuberculosis

    Directory of Open Access Journals (Sweden)

    Kogieleum Naidoo

    2011-01-01

    Full Text Available The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6.

  5. Virological features associated with the development of broadly neutralizing antibodies to HIV-1.

    Science.gov (United States)

    Moore, Penny L; Williamson, Carolyn; Morris, Lynn

    2015-04-01

    The development of a preventative HIV-1 vaccine remains a global public health priority. This will likely require the elicitation of broadly neutralizing antibodies (bNAbs) able to block infection by diverse viral strains from across the world. Understanding the pathway to neutralization breadth in HIV-1 infected humans will provide insights into how bNAb lineages arise, a process that probably involves a combination of host and viral factors. Here, we focus on the role of viral characteristics and evolution in shaping bNAbs during HIV-1 infection, and describe how these findings may be translated into novel vaccine strategies.

  6. The pathogenesis of HIV infection: stupid may not be so dumb after all.

    Science.gov (United States)

    Smith, Stephen M

    2006-09-08

    In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated by their natural hosts. Two recent studies of these models provide information, which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full understanding of pathogenesis may lead to novel therapies, which preserve the immune system without blocking virus replication.

  7. The pathogenesis of HIV infection: stupid may not be so dumb after all

    Directory of Open Access Journals (Sweden)

    Smith Stephen M

    2006-09-01

    Full Text Available Abstract In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated by their natural hosts. Two recent studies of these models provide information, which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full understanding of pathogenesis may lead to novel therapies, which preserve the immune system without blocking virus replication.

  8. In Vitro Anti-HIV Activity of a Chinese Fungus Extract

    Institute of Scientific and Technical Information of China (English)

    ZI-CHUN XIANG; YAN JIANG; SHUN-XING GUO

    2006-01-01

    Objective To investigate the inhibitory effect of the mycelium extract from a Chinese fungus (M1) on HIV-1 and its mode of action. Methods Several in vitro methods including time of action, time of addition and PCR were used to test the mode of action of M1. Results M1 inhibited acute HIV infection in vitro and was effective when it was added 12 h after infection. PCR analysis of infected cells demonstrated that M1 delayed the appearance of late product of reverse transcription and HIV was blocked before its RNA expression. Conclusion The target of M 1 is post-integration of proviral DNA.

  9. RNA LEGO: magnesium-dependent assembly of RNA building blocks through loop-loop interactions.

    Science.gov (United States)

    Horiya, Satoru; Li, Xianglan; Kawai, Gota; Saito, Ryota; Katoh, Akira; Kobayashi, Koh; Harada, Kazuo

    2002-01-01

    We describe the construction of nano-molecular assemblies using RNA building blocks the human immunodeficiency virus type 1 (HIV-1) dimerization initiation site (DIS) RNA, that forms stable base pairing through a magnesium-dependent loop-loop interaction ("kissing"). RNA building blocks containing two DIS or DIS-like hairpins connected by a two nucleotide linker self-assembled to form specific structures as observed by non-denaturing polyacrylamide gel electrophoresis (PAGE). Furthermore, observation of "real time" formation of the molecular assemblies by circular dichroism (CD) spectroscopy was attempted.

  10. Optimal Backward Perturbation Analysis for the Block Skew Circulant Linear Systems with Skew Circulant Blocks

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available We first give the block style spectral decomposition of arbitrary block skew circulant matrix with skew circulant blocks. Secondly, we obtain the singular value of block skew circulant matrix with skew circulant blocks as well. Finally, based on the block style spectral decomposition, we deal with the optimal backward perturbation analysis for the block skew circulant linear system with skew circulant blocks.

  11. Associations between HIV-related stigma, racial discrimination, gender discrimination, and depression among HIV-positive African, Caribbean, and Black women in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen; James, Llana; Tharao, Wangari; Loutfy, Mona

    2013-02-01

    Abstract African, Caribbean, and Black (ACB) women are greatly overrepresented in new HIV infections in comparison with Canada's general population. Social and structural factors such as HIV-related stigma, gender discrimination, and racial discrimination converge to increase vulnerability to HIV infection among ACB women by reducing access to HIV prevention services. Stigma and discrimination also present barriers to treatment, care, and support and may contribute to mental health problems. We administered a cross-sectional survey to HIV-positive ACB women (n=173) across Ontario in order to examine the relationships between HIV-related stigma, gender discrimination, racial discrimination, and depression. One-third of participants reported moderate/severe depression scores using the Beck Depression Inventory Fast-Screen guidelines. Hierarchical block regression, moderation, and mediation analyses were conducted to measure associations between independent (HIV-related stigma, gender discrimination, racial discrimination), moderator/mediator (social support, resilient coping), and dependent (depression) variables. Findings included: (1) HIV-related stigma was associated with increased depression; (2) resilient coping was associated with reduced depression but did not moderate the influence of HIV-related stigma on depression; and (3) the effects of HIV-related stigma on depression were partially mediated through resilient coping. HIV-related stigma, gender discrimination, and racial discrimination were significantly correlated with one another and with depression, highlighting the salience of examining multiple intersecting forms of stigma. Generalizability of findings may be limited due to nonrandom sampling. Findings emphasize the importance of multi-component interventions, including building resilient coping skills, mental health promotion and assessment, and stigma reduction programs.

  12. HIV treatment for prevention

    Directory of Open Access Journals (Sweden)

    Ambrosioni Juan

    2011-05-01

    Full Text Available Abstract "No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear. Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission. More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated

  13. HIV Treatment: What is a Drug Interaction?

    Science.gov (United States)

    ... Mental Health How to Find HIV Treatment Services HIV Treatment What is a Drug Interaction? (Last updated ... Are drug interactions a problem for people with HIV? Treatment with HIV medicines (called antiretroviral therapy or ...

  14. HIV/AIDS Clinical Trials Fact Sheet

    Science.gov (United States)

    ... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ... to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. Some ...

  15. HIV and AIDS: Medicines to Help You

    Science.gov (United States)

    ... by Audience For Women Free Publications HIV and AIDS--Medicines to Help You Share Tweet Linkedin Pin ... HIV treatment. HIV is the virus that causes AIDS. HIV stands for H uman I mmunodeficiency V ...

  16. HIV Treatment: What is a Drug Interaction?

    Science.gov (United States)

    ... to-Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: ... example, some HIV medicines may make hormonal birth control less effective. Women using hormonal contraceptives may need ...

  17. Contrasting reduced overshadowing and blocking.

    Science.gov (United States)

    Wheeler, Daniel S; Miller, Ralph R

    2007-07-01

    Preexposure of a cue without an outcome (X-) prior to compound pairings with the outcome (XZ-->O) can reduce overshadowing of a target cue (Z). Moreover, pairing a cue with an outcome (X-->O) before compound training can enhance its ability to compete with another cue (i.e., blocking). Four experiments were conducted in a conditioned bar-press suppression preparation with rats to determine whether spacing of the X- or X-->O trials would differentially affect reduced overshadowing and blocking. Experiment 1a showed that reduced overshadowing was larger with massed trials than with spaced trials. Experiment 1b found that blocking was larger with spaced trials than with massed trials. Experiments 2a and 2b indicated that these effects of trial spacing were both mediated by the associative status of the context at test. The results are interpreted in the framework of contemporary learning theories.

  18. Diversity Gain through Antenna Blocking

    Directory of Open Access Journals (Sweden)

    V. Dehghanian

    2012-01-01

    Full Text Available As part of the typical usage mode, interaction between a handheld receiver antenna and the operator's RF absorbing body and nearby objects is known to generate variability in antenna radiation characteristics through blocking and pattern changes. It is counterintuitive that random variations in blocking can result in diversity gain of practical applicability. This diversity gain is quantified from a theoretical and experimental perspective. Measurements carried out at 1947.5 MHz verify the theoretical predictions, and a diversity gain of 3.1 dB was measured through antenna blocking and based on the utilized measurement setup. The diversity gain can be exploited to enhance signal detectability of handheld receivers based on a single antenna in indoor multipath environments.

  19. Block ground interaction of rockfalls

    Science.gov (United States)

    Volkwein, Axel; Gerber, Werner; Kummer, Peter

    2016-04-01

    During a rockfall the interaction of the falling block with the ground is one of the most important factors that define the evolution of a rockfall trajectory. It steers the rebound, the rotational movement, possibly brake effects, friction losses and damping effects. Therefore, if most reliable rockfall /trajectory simulation software is sought a good understanding of the block ground interaction is necessary. Today's rockfall codes enable the simulation of a fully 3D modelled block within a full 3D surface . However, the details during the contact, i.e. the contact duration, the penetration depth or the dimension of the marks in the ground are usually not part of the simulation. Recent field tests with rocks between 20 and 80 kg have been conducted on a grassy slope in 2014 [1]. A special rockfall sensor [2] within the blocks measured the rotational velocity and the acting accelerations during the tests. External video records and a so-called LocalPositioningSystem deliver information on the travel velocity. With these data not only the flight phases of the trajectories but also the contacts with the ground can be analysed. During the single jumps of a block the flight time, jump length, the velocity, and the rotation are known. During the single impacts their duration and the acting accelerations are visible. Further, the changes of rotational and translational velocity influence the next jump of the block. The change of the rotational velocity over the whole trajectory nicely visualizes the different phases of a rockfall regarding general acceleration and deceleration in respect to the inclination and the topography of the field. References: [1] Volkwein A, Krummenacher B, Gerber W, Lardon J, Gees F, Brügger L, Ott T (2015) Repeated controlled rockfall trajectory testing. [Abstract] Geophys. Res. Abstr. 17: EGU2015-9779. [2] Volkwein A, Klette J (2014) Semi-Automatic Determination of Rockfall Trajectories. Sensors 14: 18187-18210.

  20. BCL11B is a general transcriptional repressor of the HIV-1 long terminal repeat in T lymphocytes through recruitment of the NuRD complex.

    Science.gov (United States)

    Cismasiu, Valeriu B; Paskaleva, Elena; Suman Daya, Sneha; Canki, Mario; Duus, Karen; Avram, Dorina

    2008-10-25

    In this study we provide evidence that the transcription factor BCL11B represses expression from the HIV-1 long terminal repeat (LTR) in T lymphocytes through direct association with the HIV-1 LTR. We also demonstrate that the NuRD corepressor complex mediates BCL11B transcriptional repression of the HIV-1 LTR. In addition, BCL11B and the NuRD complex repressed TAT-mediated transactivation of the HIV-1 LTR in T lymphocytes, pointing to a potential role in initiation of silencing. In support of all the above results, we demonstrate that BCL11B affects HIV-1 replication and virus production, most likely by blocking LTR transcriptional activity. BCL11B showed specific repression for the HIV-1 LTR sequences isolated from seven different HIV-1 subtypes, demonstrating that it is a general transcriptional repressor for all LTRs.

  1. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  2. OPAL 96 Blocks Lead Glass

    CERN Multimedia

    This array of 96 lead glass bricks formed part of the OPAL electromagnetic calorimeter. One half of the complete calorimeter is shown in the picture above. There were 9440 lead glass counters in the OPAL electromagnetic calorimeter. These are made of Schott type SF57 glass and each block weighs about 25 kg and consists of 76% PbO by weight. Each block has a Hamamatsu R2238 photomultiplier glued on to it. The complete detector was in the form of a cylinder 7m long and 6m in diameter. It was used to measure the energy of electrons and photons produced in LEP interactions.

  3. HIV infections in otolaryngology

    Science.gov (United States)

    Rzewnicki, Ireneusz; Olszewska, Ewa; Rogowska-Szadkowska, Dorota

    2012-01-01

    Summary HIV (human immunodeficiency virus) infection may produce no clinical symptoms for 10 years on average. However, after many years of infection most people develop symptoms that indicate progression of the disease. There are no regular characteristic symptoms or early stage, and no logical sequence of AIDS indicator disorders has been observed. People who are not aware of the infection are referred to physicians of various specializations, including otolaryngologists. It is on their knowledge about HIV infections, among other factors, that early diagnosis of the disease depends. Appropriate and quick introduction of anti-retroviral drugs may let a person with HIV live decades longer. PMID:22367140

  4. Mobility and HIV.

    Science.gov (United States)

    1999-01-01

    Migrants, refugees, and internally displaced people are vulnerable to HIV because they live in poor areas with little privacy, have different sexual relationships, and lack information about sexual health and services. In response to these problems, HIV prevention and care programs were initiated. The programs include: 1) involving migrant workers as both interviewers and outreach workers to better understand the idea of the migrants per Coordination of Action Research on Mobility and AIDS; 2) improving living conditions; 3) access of migrants to information and services; 4) improving the rights of the people; 5) increasing income; and 6) access to sexual health information that concerns exposure of HIV through different sexual partners.

  5. HIV/AIDS among African Americans

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among African Americans Format: Select One File [163K] ...

  6. HIV among Gay and Bisexual Men

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Gay and Bisexual Men Format: Select One ...

  7. HIV Among People Aged 50 and Over

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among People Aged 50 and Over Language: English ( ...

  8. HIV among Pregnant Women, Infants, and Children

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Pregnant Women, Infants, and Children Format: Select ...

  9. What is a Preventive HIV Vaccine?

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... system to recognize and effectively fight HIV in case the person is ever exposed to ... have participated in HIV vaccine studies around the world in the last 25 years, ...

  10. Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation.

    Science.gov (United States)

    Martinson, Jeffrey A; Montoya, Carlos J; Usuga, Xiomara; Ronquillo, Rollie; Landay, Alan L; Desai, Seema N

    2010-02-01

    Plasmacytoid dendritic cells (pDC) contribute to antiviral immunity mainly through recognition of microbial products and viruses via intracellular Toll-like receptor 7 (TLR7) or TLR9, resulting in the production of type I interferons (IFNs). Although interferons reduce the viral burden in the acute phase of infection, their role in the chronic phase is unclear. The presence of elevated plasma IFN-alpha levels in advanced HIV disease and its association with microbial translocation in chronic HIV infection lead us to hypothesize that IFN-alpha could contribute to immune activation. Blocking of IFN-alpha production using chloroquine, an endosomal inhibitor, was tested in a novel in vitro model system with the aim of characterizing the effects of chloroquine on HIV-1-mediated TLR signaling, IFN-alpha production, and T-cell activation. Our results indicate that chloroquine blocks TLR-mediated activation of pDC and MyD88 signaling, as shown by decreases in the levels of the downstream signaling molecules IRAK-4 and IRF-7 and by inhibition of IFN-alpha synthesis. Chloroquine decreased CD8 T-cell activation induced by aldrithiol-2-treated HIV-1 in peripheral blood mononuclear cell cultures. In addition to blocking pDC activation, chloroquine also blocked negative modulators of the T-cell response, such as indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PDL-1). Our results indicate that TLR stimulation and production of IFN-alpha by pDC contribute to immune activation and that blocking of these pathways using chloroquine may interfere with events contributing to HIV pathogenesis. Our results suggests that a safe, well-tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with highly active antiretroviral therapy to control immune activation in HIV-1 infection.

  11. Chloroquine Modulates HIV-1-Induced Plasmacytoid Dendritic Cell Alpha Interferon: Implication for T-Cell Activation▿

    Science.gov (United States)

    Martinson, Jeffrey A.; Montoya, Carlos J.; Usuga, Xiomara; Ronquillo, Rollie; Landay, Alan L.; Desai, Seema N.

    2010-01-01

    Plasmacytoid dendritic cells (pDC) contribute to antiviral immunity mainly through recognition of microbial products and viruses via intracellular Toll-like receptor 7 (TLR7) or TLR9, resulting in the production of type I interferons (IFNs). Although interferons reduce the viral burden in the acute phase of infection, their role in the chronic phase is unclear. The presence of elevated plasma IFN-α levels in advanced HIV disease and its association with microbial translocation in chronic HIV infection lead us to hypothesize that IFN-α could contribute to immune activation. Blocking of IFN-α production using chloroquine, an endosomal inhibitor, was tested in a novel in vitro model system with the aim of characterizing the effects of chloroquine on HIV-1-mediated TLR signaling, IFN-α production, and T-cell activation. Our results indicate that chloroquine blocks TLR-mediated activation of pDC and MyD88 signaling, as shown by decreases in the levels of the downstream signaling molecules IRAK-4 and IRF-7 and by inhibition of IFN-α synthesis. Chloroquine decreased CD8 T-cell activation induced by aldrithiol-2-treated HIV-1 in peripheral blood mononuclear cell cultures. In addition to blocking pDC activation, chloroquine also blocked negative modulators of the T-cell response, such as indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PDL-1). Our results indicate that TLR stimulation and production of IFN-α by pDC contribute to immune activation and that blocking of these pathways using chloroquine may interfere with events contributing to HIV pathogenesis. Our results suggests that a safe, well-tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with highly active antiretroviral therapy to control immune activation in HIV-1 infection. PMID:19949061

  12. A conformal block Farey tail

    Science.gov (United States)

    Maloney, Alexander; Maxfield, Henry; Ng, Gim Seng

    2017-06-01

    We investigate the constraints of crossing symmetry on CFT correlation functions. Four point conformal blocks are naturally viewed as functions on the upper-half plane, on which crossing symmetry acts by PSL(2, Z ) modular transformations. This allows us to construct a unique, crossing symmetric function out of a given conformal block by averaging over PSL(2, Z ). In some two dimensional CFTs the correlation functions are precisely equal to the modular average of the contributions of a finite number of light states. For example, in the two dimensional Ising and tri-critical Ising model CFTs, the correlation functions of identical operators are equal to the PSL(2, Z ) average of the Virasoro vacuum block; this determines the 3 point function coefficients uniquely in terms of the central charge. The sum over PSL(2, Z ) in CFT2 has a natural AdS3 interpretation as a sum over semi-classical saddle points, which describe particles propagating along rational tangles in the bulk. We demonstrate this explicitly for the correlation function of certain heavy operators, where we compute holographically the semi-classical conformal block with a heavy internal operator.

  13. Vagal Blocking for Obesity Control

    DEFF Research Database (Denmark)

    Johannessen, Helene; Revesz, David; Kodama, Yosuke

    2017-01-01

    BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device...

  14. Scattering matrices with block symmetries

    OpenAIRE

    Życzkowski, Karol

    1997-01-01

    Scattering matrices with block symmetry, which corresponds to scattering process on cavities with geometrical symmetry, are analyzed. The distribution of transmission coefficient is computed for different number of channels in the case of a system with or without the time reversal invariance. An interpolating formula for the case of gradual time reversal symmetry breaking is proposed.

  15. Architectures for block Toeplitz systems

    NARCIS (Netherlands)

    Bouras, Ilias; Glentis, George-Othon; Kalouptsidis, Nicholas

    1996-01-01

    In this paper efficient VLSI architectures of highly concurrent algorithms for the solution of block linear systems with Toeplitz or near-to-Toeplitz entries are presented. The main features of the proposed scheme are the use of scalar only operations, multiplications/divisions and additions, and th

  16. Enduring and Diagnosing Reader's Block.

    Science.gov (United States)

    Melanson, Lisa Stapleton

    1990-01-01

    Describes a condition called "reader's block" whereby the mind fails to comprehend the meaning of the text because of digressing thoughts. Suggests that "freereading," like freewriting, can help to clarify thoughts. Argues that it is not necessary to read things correctly the first time through. (PRA)

  17. Cryptanalysis of Selected Block Ciphers

    DEFF Research Database (Denmark)

    Alkhzaimi, Hoda A.

    ciphers initiatives, and the Competition for Authenticated Encryption: Security, Applicability, and Robustness (CAESAR). In this thesis, we first present cryptanalytic results on different ciphers. We propose attack named the Invariant Subspace Attack. It is utilized to break the full block cipher...

  18. First Degree Pacemaker Exit Block

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2016-10-01

    Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

  19. Building Blocks for Personal Brands

    Science.gov (United States)

    Thomas, Lisa Carlucci

    2011-01-01

    In this article, the author discusses the four essential building blocks for personal brands: (1) name; (2) message; (3) channels; and (4) bridges. However, outstanding building materials can only take a person so far. The author emphasizes that vision, determination, faith, a sense of humor, and humility are also required.

  20. HIV Antibody Test

    Science.gov (United States)

    ... 2 has a higher prevalence in parts of Africa.) The level of p24 antigen and the amount ... getting pregnant may opt to get tested (see Pregnancy: HIV .) The ... Teens , Young Adults , Adults , and Adults 50 and Up . ...

  1. Pregnancy and HIV infection

    Directory of Open Access Journals (Sweden)

    Mete Sucu

    2016-12-01

    Full Text Available The management of Human Immunodeficiency Virus (HIV infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinicians taking care of pregnants to have current information. Therefore, in our review we aimed to summarize the prenatal course, treatment and preventive methods for perinatal transmission of HIV. [Archives Medical Review Journal 2016; 25(4.000: 522-535

  2. HIV infection in Bophuthatswana

    African Journals Online (AJOL)

    was known about HIV infection and AIDS in the country. However, the health authorities were aware of the report ... natal, family planning and sexually transmitted diseases ..... Francis DP, Chin J. The prevention of acquired immunodeficiency.

  3. Benchmarking HIV health care

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Reekie, Joanne; Mocroft, Amanda

    2012-01-01

    ABSTRACT: BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV-patients based on four key indicators. METHODS: Four indicators of health care were...... assessed: Compliance with current guidelines on initiation of 1) combination antiretroviral therapy (cART), 2) chemoprophylaxis, 3) frequency of laboratory monitoring, and 4) virological response to cART (proportion of patients with HIV-RNA 90% of time on cART). RESULTS: 7097 Euro...... to North, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for East and Argentina (adjusted OR 0.16[95%CI 0.11-0.23, p HIV health care utilization...

  4. HIV Treatment Adherence

    Science.gov (United States)

    ... Viral Suppression Doctor, Clinical & Dental Visits Treatment Adherence Mental Health Substance Abuse Issues Sexual Health Nutrition & Food Safety Exercise Immunizations Aging with HIV/AIDS Women’s Health Housing ...

  5. HIV and Tuberculosis (TB)

    Science.gov (United States)

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Tuberculosis (TB) (Last updated 9/1/2016; last reviewed ... depends on a person’s individual circumstances. What is tuberculosis? Tuberculosis (TB) is a contagious disease that can ...

  6. HIV Resistance Testing

    Science.gov (United States)

    ... tube when ARVs are added. Genotypic resistance: The genetic code of HIV has mutations that are linked to ... phenotypic tests are somewhat quicker. GENOTYPIC TESTING The genetic code of the sample virus is compared to the ...

  7. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis B (Last updated 8/31/2016; last reviewed ... should be treated for both diseases. What is hepatitis B? Hepatitis B is a liver disease caused ...

  8. HIV and Hepatitis C

    Science.gov (United States)

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis C (Last updated 8/31/2016; last reviewed ... the medicines for any side effects. What is hepatitis C? Hepatitis C is a liver disease caused ...

  9. Reduce HIV Risk

    Science.gov (United States)

    ... Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Read More "Nursing Research" Articles Nursing Research / Improve Hospital-to-Home Transitions / Reduce ...

  10. SNFing HIV transcription

    Directory of Open Access Journals (Sweden)

    Bukrinsky Michael

    2006-08-01

    Full Text Available Abstract The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter.

  11. HIV management in practice

    African Journals Online (AJOL)

    This article briefly reviews the new South African HIV treatment ... Table I. Initiation criteria and treatment regimens in adults and children ..... Variable aetiology, but mostly caused by denial of diagnosis, religious beliefs of cure, hiding of ...

  12. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  13. Optimizing HIV drug therapy

    OpenAIRE

    Calmy, Alexandra

    2010-01-01

    The spectrum of drugs used in HIV-infected patients has dramatically changed since triple antiretroviral combinations were introduced, albeit at the expense of some severe adverse events, in 1996. Long term complications of antiretroviral drug exposure, such as HIV lipodystrophy, as well as organ-specific disease of heart and bone are, therefore, a critical issue when designing antiretroviral regimens. Because it is difficult to predict the occurrence of lipodystrophy, and because there is no...

  14. HIV resistance to raltegravir.

    Science.gov (United States)

    Clavel, Francois

    2009-11-24

    Similar to all antiretroviral drugs, failure of raltegravir-based treatment regimens to fully supress HIV replication almost invariably results in emergence of HIV resistance to this new drug. HIV resistance to raltegravir is the consequence of mutations located close to the integrase active site, which can be divided into three main evolutionary pathways: the N155H, the Q148R/H/K and the Y143R/C pathways. Each of these primary mutations can be accompanied by a variety of secondary mutations that both increase resistance and compensate for the variable loss of viral replicative capacity that is often associated with primary resistance mutations. One unique property of HIV resistance to raltegravir is that each of these different resistance pathways are mutually exclusive and appear to evolve separately on distinct viral genomes. Resistance is frequently initiated by viruses carrying mutations of the N155H pathway, followed by emergence and further dominance of viral genomes carrying mutations of the Q148R/H/K or of the Y143R/C pathways, which express higher levels of resistance. Even if some natural integrase polymorphisms can be part of this evolution process, these polymorphisms do not affect HIV susceptibility in the absence of primary mutations. Therefore, all HIV-1 subtypes and groups, together with HIV-2, are naturally susceptible to raltegravir. Finally, because interaction of integrase strand transfer inhibitors with the HIV integrase active site is comparable from one compound to another, raltegravir-resistant viruses express significant cross resistance to most other compounds of this new class of antiretroviral drugs.

  15. HIV resistance to raltegravir

    Directory of Open Access Journals (Sweden)

    Clavel François

    2009-11-01

    Full Text Available Abstract Similar to all antiretroviral drugs, failure of raltegravirbased treatment regimens to fully supress HIV replication almost invariably results in emergence of HIV resistance to this new drug. HIV resistance to raltegravir is the consequence of mutations located close to the integrase active site, which can be divided into three main evolutionary pathways: the N155H, the Q148R/H/K and the Y143R/C pathways. Each of these primary mutations can be accompanied by a variety of secondary mutations that both increase resistance and compensate for the variable loss of viral replicative capacity that is often associated with primary resistance mutations. One unique property of HIV resistance to raltegravir is that each of these different resistance pathways are mutually exclusive and appear to evolve separately on distinct viral genomes. Resistance is frequently initiated by viruses carrying mutations of the N155H pathway, followed by emergence and further dominance of viral genomes carrying mutations of the Q148R/H/K or of the Y143R/C pathways, which express higher levels of resistance. Even if some natural integrase polymorphisms can be part of this evolution process, these polymorphisms do not affect HIV susceptibility in the absence of primary mutations. Therefore, all HIV-1 subtypes and groups, together with HIV-2, are naturally susceptible to raltegravir. Finally, because interaction of integrase strand transfer inhibitors with the HIV integrase active site is comparable from one compound to another, raltegravir-resistant viruses express significant cross resistance to most other compounds of this new class of antiretroviral drugs.

  16. The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor.

    Directory of Open Access Journals (Sweden)

    Markus Helfer

    Full Text Available Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.

  17. The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor.

    Science.gov (United States)

    Helfer, Markus; Koppensteiner, Herwig; Schneider, Martha; Rebensburg, Stephanie; Forcisi, Sara; Müller, Constanze; Schmitt-Kopplin, Philippe; Schindler, Michael; Brack-Werner, Ruth

    2014-01-01

    Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.

  18. Endoscopic sphenopalatine ganglion block for pain relief

    OpenAIRE

    Murty, P. S. N.; Prasanna, Atma

    1998-01-01

    The anaesthetic effect of the sphenopalatine (SPG) block has been well utilized for intranasal topical anaesthesia but the analgesic efficacy of (SPG) block, though well documented in literature, has not been put into practice. The methods available for SPG block till date were blind as they do not visualize the foramen. Nasal endoscopies have been used to visualize the foramen for an effective block. The authors present their experience with the endoscopic sphenopalatine ganglion block for p...

  19. Pourfour Du Petit syndrome after interscalene block

    Directory of Open Access Journals (Sweden)

    Mysore Chandramouli Basappji Santhosh

    2013-01-01

    Full Text Available Interscalene block is commonly associated with reversible ipsilateral phrenic nerve block, recurrent laryngeal nerve block, and cervical sympathetic plexus block, presenting as Horner′s syndrome. We report a very rare Pourfour Du Petit syndrome which has a clinical presentation opposite to that of Horner′s syndrome in a 24-year-old male who was given interscalene block for open reduction and internal fixation of fracture upper third shaft of left humerus.

  20. Pourfour Du Petit syndrome after interscalene block.

    Science.gov (United States)

    Santhosh, Mysore Chandramouli Basappji; Pai, Rohini B; Rao, Raghavendra P

    2013-04-01

    Interscalene block is commonly associated with reversible ipsilateral phrenic nerve block, recurrent laryngeal nerve block, and cervical sympathetic plexus block, presenting as Horner's syndrome. We report a very rare Pourfour Du Petit syndrome which has a clinical presentation opposite to that of Horner's syndrome in a 24-year-old male who was given interscalene block for open reduction and internal fixation of fracture upper third shaft of left humerus.

  1. Limiting Spectral Distribution of Block Matrices with Toeplitz Block Structure

    CERN Document Server

    Basu, Riddhipratim; Ganguly, Shirshendu; Hazra, Rajat Subhra

    2011-01-01

    We study two specific symmetric random block Toeplitz (of dimension $k \\times k$) matrices: where the blocks (of size $n \\times n$) are (i) matrices with i.i.d. entries, and (ii) asymmetric Toeplitz matrices. Under suitable assumptions on the entries, their limiting spectral distributions (LSDs) exist (after scaling by $\\sqrt{nk}$) when (a) $k$ is fixed and $n \\to\\infty$ (b) $n$ is fixed and $k\\rightarrow \\infty$ (c) $n$ and $k$ go to $\\infty$ simultaneously. Further the LSD's obtained in (a) and (b) coincide with those in (c) when $n$ or respectively $k$ tends to infinity. This limit in (c) is the semicircle law in case (i). In Case (ii) the limit is related to the limit of the random symmetric Toepiltz matrix as obtained by Bryc et al.(2006) and Hammond and Miller(2005).

  2. Coping with viral diversity in HIV vaccine design.

    Directory of Open Access Journals (Sweden)

    David C Nickle

    2007-04-01

    Full Text Available The ability of human immunodeficiency virus type 1 (HIV-1 to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT] and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT(+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.

  3. HIV, poverty and women.

    Science.gov (United States)

    Rodrigo, Chaturaka; Rajapakse, Senaka

    2010-03-01

    This review examines the interactions of financial status and HIV and its implications for women. MEDLINE and Google scholar were searched using the keywords 'women', 'poverty' and 'HIV' in any field of the article. The search was limited to articles published in English over the last 10 years. The first section of the article tries to establish whether poverty or wealth is a risk factor for HIV. There is credible evidence for both arguments. While wealth shows an increased risk for both sexes, poverty places women at a special disadvantage. The second section explains how the financial status interacts with other 'non biological' factors to put women at increased risk. While discrimination based on these factors disadvantage women, there are some paradoxical observations that do not fit with the traditional line of explanation (e.g. paradoxical impact of wealth and education on HIV). The final section assesses the impact of HIV in driving poverty and the role of women in interventional programmes. The specific impact of poverty on females in families living with HIV is less explored. Though microfinance initiatives to empower women are a good idea in theory, the actual outcome of such a programme is less convincing.

  4. HIV TRANSMISSION BREAST-FEEDING AND HIV: AN UPDATE

    African Journals Online (AJOL)

    Enrique

    2004-11-02

    Nov 2, 2004 ... THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE. November 2004 ... Breast-feeding is a route of transmission of HIV from an infected mother to her infant. However ..... Early introduction of non-human milk and solid.

  5. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

    Directory of Open Access Journals (Sweden)

    Phanourios Tamamis

    Full Text Available The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  6. Enhanced neutralization of HIV by antibodies displayed on the S-layer of Caulobacter crescentus.

    Science.gov (United States)

    Duval, Mark; Lewis, Christopher J; Nomellini, John F; Horwitz, Marc S; Smit, John; Cavacini, Lisa A

    2011-12-01

    Innovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacterium Caulobacter crescentus and its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed on Caulobacter was as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary, C. crescentus, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.

  7. Chemokines and chemokine receptors in HIV infection: Role in pathogenesis and therapeutics

    Directory of Open Access Journals (Sweden)

    Suresh P

    2006-01-01

    Full Text Available Chemokines are known to function as regulatory molecules in leukocyte maturation, traffic, homing of lymphocytes and in the development of lymphoid tissues. Besides these functions in the immune system, certain chemokines and their receptors are involved in HIV pathogenesis. In order to infect a target cell, the HIV envelope glycoprotein gp120 has to interact with the cellular receptor CD-4 and co-receptor, CC or CXC chemokine receptors. Genetic findings have yielded major insights into the in vivo roles of individual co-receptors and their ligands in providing resistance to HIV infection. Mutations in chemokine receptor genes are associated with protection against HIV infections and also involved in delayed progression to AIDS in infected individuals. Blocking of chemokine receptors interrupts HIV infection in vitro and this offers new options for therapeutic strategies. Approaches have been made to study the CCR-5 inhibitors as antiviral therapies and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission. Immune strategies aimed at generating anti-CCR-5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV- protective immunity. It also remains to be seen how these types of agents will act in synergy with existing HIV-1 targeted anti viral, or those currently in developments. Beyond providing new perspectives in fundamental aspects of the HIV-1 transmission and pathogenesis, chemokines and their receptors suggest new areas for developing novel therapeutic and preventive strategies against HIV infections. Studies in this review were identified through a search for relevant literature in the pubmed database of the national library of medicine. In this review, some developments in chemokine research with particular focus on their roles in HIV pathogenesis, resistance and therapeutic applications have been discussed.

  8. Monocytes from HIV+ individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration

    Science.gov (United States)

    MAISA, Anna; HEARPS, Anna C.; ANGELOVICH, Thomas A.; PEREIRA, Candida F.; ZHOU, Jingling; SHI, Margaret D.Y.; PALMER, Clovis S.; MULLER, William A.; CROWE, Suzanne M.; JAWOROWSKI, Anthony

    2016-01-01

    Design HIV+ individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent of antiretroviral therapy and traditional risk factors. Monocytes play a central role in the development of atherosclerosis, and HIV-related chronic inflammation and monocyte activation may contribute to increased atherosclerosis, but the mechanisms are unknown. Methods Using an in vitro model of atherosclerotic plaque formation, we measured the transendothelial migration of purified monocytes from age-matched HIV+ and uninfected donors and examined their differentiation into foam cells. Cholesterol efflux and the expression of cholesterol metabolism genes were also assessed. Results Monocytes from HIV+ individuals showed increased foam cell formation compared to controls (18.9% vs 0% respectively, p=0.004) and serum from virologically suppressed HIV+ individuals potentiated foam cell formation by monocytes from both uninfected and HIV+ donors. Plasma TNF levels were increased in HIV+ vs control donors (5.9 vs 3.5 pg/ml, p=0.02) and foam cell formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed HIV+ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (p=0.02). Conclusions Monocytes from HIV+ individuals show impaired cholesterol efflux and are primed for foam cell formation following trans-endothelial migration. Factors present in HIV+ serum, including elevated TNF levels, further enhance foam cell formation. The pro-atherogenic phenotype of monocytes persists in virologically suppressed HIV+ individuals and may contribute mechanistically to increased atherosclerosis in this population. PMID:26244384

  9. 2´,3´-Dialdehyde of ATP, ADP, and adenosine inhibit HIV-1 reverse transcriptase and HIV-1 replication.

    Science.gov (United States)

    Schachter, Julieta; Valadao, Ana Luiza Chaves; Aguiar, Renato Santana; Barreto-de-Souza, Victor; Rossi, Atila Duque; Arantes, Pablo Ricardo; Verli, Hugo; Quintana, Paula Gabriela; Heise, Norton; Tanuri, Amilcar; Bou-Habib, Dumith Chequer; Persechini, Pedro Muanis

    2014-01-01

    The 2´3´-dialdehyde of ATP or oxidized ATP (oATP) is a compound known for specifically making covalent bonds with the nucleotide-binding site of several ATP-binding enzymes and receptors. We investigated the effects of oATP and other oxidized purines on HIV-1 infection and we found that this compound inhibits HIV-1 and SIV infection by blocking early steps of virus replication. oATP, oxidized ADP (oADP), and oxidized Adenosine (oADO) impact the natural activity of endogenous reverse transcriptase enzyme (RT) in cell free virus particles and are able to inhibit viral replication in different cell types when added to the cell cultures either before or after infection. We used UFLC-UV to show that both oADO and oATP can be detected in the cell after being added in the extracellular medium. oATP also suppresses RT activity and replication of the HIV-1 resistant variants M184V and T215Y. We conclude that oATP, oADP and oADO display anti HIV-1 activity that is at in least in part due to inhibitory activity on HIV-1 RT.

  10. Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.

    Directory of Open Access Journals (Sweden)

    Matthew J Pace

    Full Text Available Despite the effectiveness of highly active antiretroviral therapy (HAART in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response.

  11. Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly.

    Science.gov (United States)

    Khamaikawin, Wannisa; Saoin, Somphot; Nangola, Sawitree; Chupradit, Koollawat; Sakkhachornphop, Supachai; Hadpech, Sudarat; Onlamoon, Nattawat; Ansari, Aftab A; Byrareddy, Siddappa N; Boulanger, Pierre; Hong, Saw-See; Torbett, Bruce E; Tayapiwatana, Chatchai

    2015-08-25

    Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (Ank(GAG)1D4) and the zinc finger protein (2LTRZFP) have recently been characterized as intracellular antivirals, but these molecules, used individually, do not completely block HIV-1 replication and propagation. The capsid-binder Ank(GAG)1D4, which inhibits HIV-1 assembly, does not prevent the genome integration of newly incoming viruses. 2LTRZFP, designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1 integration, would have no antiviral effect on HIV-1-infected cells. However, simultaneous expression of these two molecules should combine the advantage of preventive and curative treatments. To test this hypothesis, the genes encoding the N-myristoylated Myr(+)Ank(GAG)1D4 protein and the 2LTRZFP were introduced into human T-cells, using a third-generation lentiviral vector. SupT1 cells stably expressing 2LTRZFP alone or with Myr(+)Ank(GAG)1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)Ank(GAG)1D4 vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral effect. Resistance to viral infection was also observed in primary human CD4+ T-cells stably expressing Myr(+)Ank(GAG)1D4, and challenged with HIV-1, SIVmac, or SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are promising antiviral agents for anti-HIV-1 gene therapy.

  12. On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

    KAUST Repository

    Pestana, Jennifer

    2014-01-01

    Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... abuse by any route (not just injection) can put a person at risk for getting HIV. Drug ... and can lead to unsafe sexual practices, which put people at risk for getting HIV or transmitting ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Prevention Recovery Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search ... the link between drug abuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the ... clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Medical & Health Professionals Patients & Families Parents & Educators Children & ... In addition, infected pregnant women can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... has shown that HIV causes greater injury to cells in the brain and cognitive impairment among methamphetamine abusers than among HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ... poor decision making, which can result in risky sexual behaviors and HIV infection. Although the characters are fictional, ...

  19. HIV/AIDS and Infections

    Science.gov (United States)

    Having HIV/AIDS weakens your body's immune system. It destroys the white blood cells that fight infection. This puts ... such as crypto (cryptosporidiosis) and toxo (toxoplasmosis) Having HIV/AIDS can make infections harder to treat. People ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Research Post-Award Concerns General Information Grant & Contract Application Process Funding Priorities Research Training News & Events News ... What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS ( ... is crucial to the normal function of the human immune system. Loss of these CD4+ cells in ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the ... on HIV/AIDS and related diseases, counseling and testing services, and referrals for medical and social services. ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the link between drug abuse and HIV infection. It contains information for young people, parents and teachers, ... present time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to ...

  4. Drugs + HIV, Learn the Link

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    Full Text Available ... depict the devastating consequences of compromised judgment and critical thinking that can result from drug use. Young ... HIV epidemic. As we learn more about the critical connection between drug abuse and HIV/AIDS and ...

  5. Drugs + HIV, Learn the Link

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    Full Text Available ... can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of ... and for Veterans and the public. Past Public Service Announcements Jack & Jill : Campaign launch, December 1, 2001. ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune ... infected pregnant women can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... or decrease symptoms of illness. To learn about current statistics of HIV in the United States, please ... programs also serve an important role in providing current information on HIV/AIDS and related diseases, counseling ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the ... on HIV/AIDS and related diseases, counseling and testing services, and referrals for medical and social services. ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... membranes of an uninfected person. In addition, infected pregnant women can pass HIV to their babies during ... HIV infection in the United States. Drugs can change the way the brain works, disrupting the parts ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... frequently suffer dangerous weight loss, diarrhea, and a type of cancer called Kaposi's sarcoma. 1 Some hopeful ... of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... abuse and HIV infection. It contains information for young people, parents and teachers, and the media with links ... 177(1):355-361. How are Teens Affected? Young people are at risk for contracting HIV. In general, ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risky choices that ultimately led to an HIV-positive diagnosis. The "After the Party" PSA tells the story of the girl who is HIV-positive (from the "Text Message" spot) from her own ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of an uninfected person. In addition, infected pregnant women can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV destroys a certain kind of white blood cell that is crucial to the normal function of the human immune system. Loss of these CD4+ cells in people with HIV is a key predictor ...

  15. Sex and Sexuality and HIV

    Science.gov (United States)

    ... DO protect against HIV: abstinence (not having sex) male condom female condom Birth control options that DO NOT protect against HIV: oral contraceptive ("the pill") Depo-Provera (shot) emergency contraception ("morning- ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... are at risk for contracting HIV. In general, middle and late teen years are when young people ... link between drug abuse and HIV. Post on Facebook or Twitter ; add photos to your Flickr , Pinterest , ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as ... as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media tools offer new ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV destroys a certain kind of white blood cell that is crucial to the normal function of the human immune system. Loss of these CD4+ cells in people with HIV is a key predictor ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... Children, Youth and Families The American Academy of Child & Adolescent Psychiatry (AACAP) The United Negro College Fund, ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... got high at a party and made risky choices that ultimately led to an HIV-positive diagnosis. ... of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... causes AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune system for which there ... causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing ... please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/ ...

  3. HIV MARCH MAKE UP 01

    African Journals Online (AJOL)

    Winnie

    2006-03-03

    Mar 3, 2006 ... THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE. MARCH 2006. 39 ... from HIV and EKD are excluded from long-term dialysis programmes. ... actually worsen the patient's nutritional status. Survival rates.

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the link between drug abuse and HIV infection. It contains information for young people, parents and teachers, ... present time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... increasingly at risk for HIV infection through risky sexual behaviors. NIDA researchers have studied and continue to study the links between drug abuse and HIV/AIDS. In the early years of ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... 1 Some hopeful news is that, in recent years, HIV is no longer a death sentence, as ... contracting HIV. In general, middle and late teen years are when young people engage in risk-taking ...

  7. HIV/AIDS Clinical Trials

    Science.gov (United States)

    ... Republic Côte D'Ivoire Denmark Djibouti Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Estonia Ethiopia Fiji ... Syphilis Toxoplasmosis Varicella-Zoster Virus (Chickenpox/Shingles) Prevention Research HIV Prevention in Substance Users HIV Preventive Vaccines ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS ( ... is crucial to the normal function of the human immune system. Loss of these CD4+ cells in ...

  9. Graphs obtained from collections of blocks

    Directory of Open Access Journals (Sweden)

    Colton Magnant

    2015-03-01

    Full Text Available Given a collection of $d$-dimensional rectangular solids called blocks, no two of which sharing interior points, construct a block graph by adding a vertex for each block and an edge if the faces of the two corresponding blocks intersect nontrivially.  It is known that if $d \\geq 3$, such block graphs can have arbitrarily large chromatic number.  We prove that the chromatic number can be bounded with only a mild restriction on the sizes of the blocks.  We also show that block graphs of block configurations arising from partitions of $d$-dimensional hypercubes into sub-hypercubes are at least $d$-connected.  Bounds on the diameter and the hamiltonicity of such block graphs are also discussed.

  10. Living with HIV: Patients Perspective

    Centers for Disease Control (CDC) Podcasts

    2009-06-04

    This podcast showcases three people who are living with HIV. The patients share their experiences of being diagnosed with HIV, of the treatments they are undergoing, and on taking responsibility for their health.  Created: 6/4/2009 by Division of HIV and AIDS Prevention (DHAP), National Center for HIV, Hepatitis, STD, and Tuberculosis Prevention ( NCHHSTP).   Date Released: 6/4/2009.

  11. HIV Associated Lupus Like Nephropathy

    OpenAIRE

    2014-01-01

    Background Human immunodeficiency virus type 1 (HIV-1)-seropositive patients are at a high risk for the development of a variety of acute and chronic renal diseases. Most patients with HIVAN are of African descent, presenting late in the course of their HIV-1 infection. The only reliable test to establish or rule out the presence of HIVAN (HIV associated nephropathy) is renal biopsy. The most common lesion associated with HIV is a focal segmental glomeruloscelerosis, but several times, other ...

  12. Silibinin inhibits HIV-1 infection by reducing cellular activation and proliferation.

    Science.gov (United States)

    McClure, Janela; Lovelace, Erica S; Elahi, Shokrollah; Maurice, Nicholas J; Wagoner, Jessica; Dragavon, Joan; Mittler, John E; Kraft, Zane; Stamatatos, Leonidas; Stamatatos, Leonidis; Horton, Helen; De Rosa, Stephen C; Coombs, Robert W; Polyak, Stephen J

    2012-01-01

    Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL), a major component of silymarin, displays anti-HCV effects in humans and also inhibits T-cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+ cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4 and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest that SIL attenuated cellular functions involved in T-cell activation, proliferation, and HIV-1 infection. Silymarin-derived compounds provide cytoprotection by suppressing virus infection, immune activation, and inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV co-infected subjects.

  13. Silibinin inhibits HIV-1 infection by reducing cellular activation and proliferation.

    Directory of Open Access Journals (Sweden)

    Janela McClure

    Full Text Available Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum block hepatitis C virus (HCV infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL, a major component of silymarin, displays anti-HCV effects in humans and also inhibits T-cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+ cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4 and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest that SIL attenuated cellular functions involved in T-cell activation, proliferation, and HIV-1 infection. Silymarin-derived compounds provide cytoprotection by suppressing virus infection, immune activation, and inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV co-infected subjects.

  14. A conformal block Farey tail

    CERN Document Server

    Maloney, Alexander; Ng, Gim Seng

    2016-01-01

    We investigate the constraints of crossing symmetry on CFT correlation functions. Four point conformal blocks are naturally viewed as functions on the upper-half plane, on which crossing symmetry acts by PSL(2,Z) modular transformations. This allows us to construct a unique, crossing symmetric function out of a given conformal block by averaging over PSL(2,Z). In some two dimensional CFTs the correlation functions are precisely equal to the modular average of the contributions of a finite number of light states. For example, in the two dimensional Ising and tri-critical Ising model CFTs, the correlation functions of identical operators are equal to the PSL(2,Z) average of the Virasoro vacuum block; this determines the 3 point function coefficients uniquely in terms of the central charge. The sum over PSL(2,Z) in CFT2 has a natural AdS3 interpretation as a sum over semi-classical saddle points, which describe particles propagating along rational tangles in the bulk. We demonstrate this explicitly for the corre...

  15. Inhibition of HIV-1 replication with stable RNAi-mediated knockdown of autophagy factors

    NARCIS (Netherlands)

    J.J.M. Eekels (Julia J. M.); S. Sagnier (Sophie); D. Geerts (Dirk); R.E. Jeeninga (Rienk); M. Biard-Piechaczyk (Martine); B. Berkhout (Ben)

    2012-01-01

    textabstractAbstract. Autophagy is a cellular process leading to the degradation of cytoplasmic components such as organelles and intracellular pathogens. It has been shown that HIV-1 relies on several components of the autophagy pathway for its replication, but the virus also blocks late steps of a

  16. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers

    1997-01-01

    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV, as well as other information about the science of drug abuse is available at NIDA's home page . blog.AIDS.gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction have been linked with HIV/AIDS ... this regard, the role that non-injection drug abuse plays in the spread of HIV is less ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Plan Search Share Print Home » News & Events » Public Education Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug abuse are among the main factors in the spread of HIV infection in the ...

  20. When One Partner Is HIV+

    Science.gov (United States)

    ... Translate Text Size Print When One Partner Is HIV+ What is a “mixed-status” Relationship? A " ... but you can minimize it. Tips for the HIV-negative Partner If you are the HIV-negative ...

  1. Drugs + HIV, Learn the Link

    Science.gov (United States)

    ... young people engage in risk-taking and sensation-seeking behaviors. Unsafe sexual practices increase a person's risk of ... HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... young people engage in risk-taking and sensation-seeking behaviors. Unsafe sexual practices increase a person's risk of ... HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... people affected by HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This site provides information both for health care providers and for Veterans and the ... Public Service Announcements Jack & Jill : Campaign launch, ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. ... link between drug abuse and HIV. Post on Facebook or Twitter ; add photos to your Flickr , Pinterest , ...

  5. Raman spectroscopic study on structure of human immunodeficiency virus (HIV) and hypericin-induced photosensitive damage of HIV

    Institute of Scientific and Technical Information of China (English)

    XU; Yiming; LU; Chuanzong

    2005-01-01

    , which was the possible binding site to hypericin, whereas the viral lipids bilayers were still probably in the liquid ordered phase or the gel phase. So the space structure of HIV1-HIV2 was damaged under the experimental conditions, which might block viral infection and inhibit its growth and breeding. It is apparent that the laser Raman spectra have provided certain direct evidence at the molecular level for photosensitive damage of HIV1-HIV2.

  6. Vaccination scars in HIV infected patients – does vaccinia vaccination confer protection against HIV?

    DEFF Research Database (Denmark)

    Jespersen, Sanne; Hønge, Bo Langhoff; Medina, Candida

    Vaccination scars in HIV infected patients – does vaccinia vaccination confer protection against HIV?......Vaccination scars in HIV infected patients – does vaccinia vaccination confer protection against HIV?...

  7. HIV-1 vaccines

    Science.gov (United States)

    Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

    2014-01-01

    The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

  8. HIV Sequence Compendium 2015

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas Kenneth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Cristian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Pennsylvania, Philadelphia, PA (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-05

    This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  9. Natural anti-CCR5 antibodies in HIV-infection and -exposure

    Directory of Open Access Journals (Sweden)

    Lopalco Lucia

    2010-01-01

    Full Text Available Abstract Natural antibodies constitute a first-line of defence against pathogens; they may also play other roles in immune regulation and homeostasis, through their ability to bind host antigens, surface molecules and receptors. Natural anti-CCR5 antibodies can be decisive in preventing HIV infection in mucosal tissues and offer prompt and effective protection just at major sites of virus entry. Among natural anti-CCR5 antibodies, IgG and IgA to the ECL1 domain have been shown to block HIV effectively and durably without causing harm to the host. Their biological properties and their uncommon generation in subsets of HIV-infected and HIV-exposed individuals (so called ESN will be introduced and discussed, with the aim at exploiting their potential in therapy and prevention.

  10. Broadly Neutralizing Antibodies Against HIV: New Insights to Inform Vaccine Design.

    Science.gov (United States)

    Sadanand, Saheli; Suscovich, Todd J; Alter, Galit

    2016-01-01

    HIV-1 poses immense immunological challenges to the humoral immune response because of its ability to shield itself and replicate and evolve rapidly. Although most currently licensed vaccines provide protection via the induction of antibodies (Abs) that can directly block infection ( 1 ), 30 years of HIV-1 vaccine research has failed to successfully elicit such Abs against globally relevant HIV strains. However, mounting evidence suggests that these broadly neutralizing antibodies (bNAbs) do emerge naturally in a significant fraction of infected subjects, albeit after years of infection, indicating that these responses can be selected naturally by the immune response but take long periods of time to evolve. We review the basic structural characteristics of broadly neutralizing antibodies and how they recognize the virus, and we discuss new vaccination strategies that aim to mimic natural evolution to guide B cells to produce protective Abs against HIV-1.

  11. Hillslope-derived blocks retard river incision

    Science.gov (United States)

    Shobe, Charles M.; Tucker, Gregory E.; Anderson, Robert S.

    2016-05-01

    The most common detachment-limited river incision models ignore the effects of sediment on fluvial erosion, yet steep reaches of mountain rivers often host clusters of large (>1 m) blocks. We argue that this distribution of blocks is a manifestation of an autogenic negative feedback in which fast vertical river incision steepens adjacent hillslopes, which deliver blocks to the channel. Blocks inhibit incision by shielding the bed and enhancing form drag. We explore this feedback with a 1-D channel-reach model in which block delivery by hillslopes depends on the river incision rate. Results indicate that incision-dependent block delivery can explain the block distribution in Boulder Creek, Colorado. The proposed negative feedback may significantly slow knickpoint retreat, channel adjustment, and landscape response compared to rates predicted by current theory. The influence of hillslope-derived blocks may complicate efforts to extract base level histories from river profiles.

  12. Demographic Data - MDC_BlockGroup

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade County Census 2000 Block Groups. A census Block Group is a statistical subdivision of a census Tract consisting of a cluster of...

  13. Demographic Data - MDC_BlockGroup

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — A polygon feature class of Miami-Dade County Census 2000 Block Groups. A census Block Group is a statistical subdivision of a census Tract consisting of a cluster...

  14. Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity

    OpenAIRE

    Song, Ruijiang; Oren, Deena A.; Franco, David; Seaman, Michael S; Ho, David D.

    2013-01-01

    Ibalizumab is a humanized monoclonal antibody that binds human CD4—a key receptor for HIV—and blocks HIV-1 infection. However, HIV-1 strains with mutations resulting in loss of an N-linked glycan from the V5 loop of the envelope protein gp120 are resistant to ibalizumab. Previous structural analysis suggests that this glycan fills a void between the gp120 V5 loop and the ibalizumab L chain, perhaps causing steric hindrance that disrupts viral entry. If this void contributes to HIV-1 resistanc...

  15. HIV-Associated Neurocysticercosis.

    Science.gov (United States)

    Anand, Kuljeet Singh; Wadhwa, Ankur; Garg, Jyoti; Mahajan, Rakesh Kumar

    2015-01-01

    Few cases of HIV and neurocysticercosis co-infection have been reported till date. The symptomatic manifestation of cysticercosis may be further reduced by interactions between the 2 disease processes. In patients with HIV, the diagnosis of neurocysticercosis is challenging and management must be individualized depending on the stage and the coexistent opportunistic conditions. We present 2 such cases. First was a 35-year-old driver seropositive for HIV-1 presented with complex partial seizures and a CD4 count of 530 cells/mm(3). The second case was a 40-year-old businessman with a CD4 count of 350 cells/mm(3). Both of them had multiple parenchymal lesions, with 1 being a large cystic lesion. Relatively high CD4 count and a positive enzyme-linked immunosorbent assay increased the likelihood for diagnosis and treatment. Both of our patients received cysticidal therapy, and none of them deteriorated with treatment.

  16. Slickenside developed in chert block

    Science.gov (United States)

    Ando, J.; Hayasaka, Y.; Nishiwaki, T.

    2011-12-01

    We observe the microstructures of slickenside developed in chert block mainly with a TEM, in order to clarify generation mechanism of the slickenside. This chert block occurs in the Jurassic accretionary complex in eastern Yamaguchi Prefecture, Japan. The complex, chaotic sediment, is composed of allochthonous blocks, mainly of chert, limestone, sandstone and mudstone in the argillaceous matrix. The color of the undeformed chert is pale blue to white, while the surface of slickenside is black. The stereo microscopy indicates the top surface of slickenside is covered with a transparent material, whose composition is mainly Si, measured by EPMA. The striation is well developed on the transparent-Si-material. We made thin sections, parallel and perpendicular to striation and slickenside, respectively. On the thin sections, the elongated quartz grains are oriented obliquely to the slickenside with 20-30 degree. Many fluid inclusions, which represent healed microcracks, are observed within the quartz grains. These quartz grains show strong undulose extinction and bulging-recrystallization. Apatite grains are also observed as a main constituent mineral. We made TEM foils from the above thin section by FIB. TEM observation indicates the amorphous layer with several ten nanometers in width distributes along the slickenside. (We speculate the most part of the amorphous layer are taken away during polishing of the thin section, because the strength of the amorphous layer is weak. Therefore we now make thin section again with care.) The tangled dislocations are developed within the quartz grains. They make subgrains with ca. 1 micrometer in size. These results suggest the slickenside was generated by the frictional melting of quartz grains on slip plane under very high stress condition, same as pseudotachylyte.

  17. Identification of host proteins associated with HIV-1 preintegration complexes isolated from infected CD4+ cells.

    Science.gov (United States)

    Raghavendra, Nidhanapati K; Shkriabai, Nikolozi; Graham, Robert Lj; Hess, Sonja; Kvaratskhelia, Mamuka; Wu, Li

    2010-08-11

    block HIV-1 integration.

  18. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  19. Spatial Epidemiology of HIV among Injection Drug Users in Tijuana, Mexico

    Science.gov (United States)

    Brouwer, Kimberly C.; Rusch, Melanie L.; Weeks, John R.; Lozada, Remedios; Vera, Alicia; Magis-Rodríguez, Carlos; Strathdee, Steffanie A.

    2012-01-01

    The northwest border city of Tijuana is Mexico’s fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006–2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p=0.001). HIV cases at baseline (n=47) most strongly clustered by drug injection sites (Z-Score −6.173; p < 0.001), with a 16 km2 hotspot near the Mexico/U.S. border, encompassing the red-light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July–December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs. PMID:23606753

  20. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  1. Practical Binary Adaptive Block Coder

    CERN Document Server

    Reznik, Yuriy A

    2007-01-01

    This paper describes design of a low-complexity algorithm for adaptive encoding/ decoding of binary sequences produced by memoryless sources. The algorithm implements universal block codes constructed for a set of contexts identified by the numbers of non-zero bits in previous bits in a sequence. We derive a precise formula for asymptotic redundancy of such codes, which refines previous well-known estimate by Krichevsky and Trofimov, and provide experimental verification of this result. In our experimental study we also compare our implementation with existing binary adaptive encoders, such as JBIG's Q-coder, and MPEG AVC (ITU-T H.264)'s CABAC algorithms.

  2. HIV infection in the elderly

    Directory of Open Access Journals (Sweden)

    Nancy Nguyen

    2008-09-01

    Full Text Available Nancy Nguyen1, Mark Holodniy21University of the Pacific School of Pharmacy and Health Sciences, Stockton, CA, USA; 2VA Palo Alto Health Care System, Palo Alto, CA, USAAbstract: In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient.Keywords: HIV, epidemiology, treatment, aging, review

  3. HIV in women

    Directory of Open Access Journals (Sweden)

    Mulcahy F

    2012-11-01

    Full Text Available Globally over 50% of HIV-infected individuals are women. With the widespread use of HAART, we can expect women to have mortality rates approaching normal. Indeed, studies have shown that women may expect a slower disease progression than men following seroconversion; furthermore, it appears that female who injects drugs can live longer than their male counterparts. However, other studies from cohort analysis have reported worse outcomes in women. In essence, many studies are consistently underpowered to adequately address these questions. The proportion of women in clinical trials remains at 20 to 30%, with pregnancy potential being a major exclusion factor. Hence, many questions remain unanswered. Recent data suggest women are more likely to present late with a new AIDS diagnosis. Why this should be the case is not well understood. In addition, HIV-positive women should have the same access to reproduction health as their negative counterparts, but unfortunately many inequalities remain. Advise on contraception and fertility services are very variable across both the developed and developing world. Data are limited on the most appropriate use of contraceptives in the presence of HAART, the possible drug interactions and possible increased risk of HIV transmission. There remain significant differences in guidelines regarding prevention of mother-to-child transmission (MTCT across Europe, and implications of stopping and starting HAART for MTCT have not been adequately addressed. The mode of timing of delivery, and the effect of length of time of ruptured membranes on this decision is also contentious. Further issues relate to the desire for HIV-positive women to breastfeed in the setting of HIV viral suppression, where some guidelines now support women in this situation and others categorically would inform child protection authorities. Finally as women age it is more difficult to separate the effect of the menopause and its symptoms from the

  4. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

    Science.gov (United States)

    2012-01-01

    Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) of HIV-demented (HIV-D) and HIV-nondemented (HIV-ND) patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF) in the CSF of HIV-D patients (n = 7) but not in that of HIV-ND patients (n = 7). Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1)-activated human fetal astrocytes, HIV-1 (Ba-L)-infected macrophages, and HIV-1 (NLENG1)-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold) for activated peripheral blood mononuclear cells (PBMC), suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK) signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting of chemokines in

  5. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

    Directory of Open Access Journals (Sweden)

    Mehla Rajeev

    2012-10-01

    Full Text Available Abstract Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF of HIV-demented (HIV-D and HIV-nondemented (HIV-ND patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF in the CSF of HIV-D patients (n = 7 but not in that of HIV-ND patients (n = 7. Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1-activated human fetal astrocytes, HIV-1 (Ba-L-infected macrophages, and HIV-1 (NLENG1-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold for activated peripheral blood mononuclear cells (PBMC, suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting

  6. HIV and Ischemic Heart Disease.

    Science.gov (United States)

    Vachiat, Ahmed; McCutcheon, Keir; Tsabedze, Nqoba; Zachariah, Don; Manga, Pravin

    2017-01-03

    The association of coronary heart disease (CHD) and human immunodeficiency virus (HIV) infection has been well recognized for many years. The etiology of the increased prevalence of CHD in HIV-infected populations is the result of complex interactions among the viral infection, host factors, traditional risk factors, and therapies for HIV. As the HIV population is living longer, largely attributable to combination antiretroviral therapy, there is concern about the effect of the rising prevalence of CHD on morbidity and mortality, as well its effect on health systems around the world. This review will highlight the epidemiological evidence linking HIV infection and CHD. It will also focus on our current understanding of the pathogenesis and factors associated with HIV infection and CHD. In addition, the review will highlight modes of presentation and management strategies for mitigating risk and treatment of HIV-positive patients presenting with CHD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. What is a Therapeutic HIV Vaccine?

    Science.gov (United States)

    ... Understanding HIV/AIDS Drugs Clinical Trials Apps Home Guidelines Understanding HIV/AIDS Drugs Clinical Trials Apps skip to content HIV Overview Home Understanding HIV/AIDS Fact Sheets What is a Therapeutic HIV Vaccine? Search Search Table of Contents Table ...

  8. What is an Investigational HIV Drug?

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... vaccines to treat or prevent HIV. In most cases, an investigational drug ... Medical research studies—also called clinical trials—are done to evaluate ...

  9. What is a Therapeutic HIV Vaccine?

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... system to recognize and effectively fight HIV in case the virus ever enters the ... database of ClinicalTrials.gov study summaries. Click on the title of any trial ...

  10. Advancing Biosocial Pedagogy for HIV Education

    Science.gov (United States)

    Davis, Mark David McGregor

    2011-01-01

    This article develops the concept of biosocial pedagogy in HIV education for this era of expanding biomedical forms of HIV control. With reference to critical pedagogy and teaching and learning materials addressing HIV treatment and prevention, I explain how HIV education can problematize its own role in HIV control. I also discuss how educational…

  11. Writer's block in a Chinese sample.

    Science.gov (United States)

    Lee, Sy-Ying; Krashen, Stephen

    2003-10-01

    To assess whether writer's block occurs in languages other than English, a Chinese language translation of Rose's Writer's Block questionnaire was administered to 98 university students in Taiwan. Analysis suggests that writer's block occurs for Chinese students, and, as in English, it is related to premature editing and to a lack of strategies for dealing with complex writing tasks.

  12. Micellization and Dynamics of a Block Copolymer

    DEFF Research Database (Denmark)

    Hvidt, Søren

    2006-01-01

    Triblock copolymers of the type EPE, where E and P denote ethylene oxide and propylene oxide blocks, respectively, are industrially important copolymers often called Pluronics or Poloxamers. EPE copolymers form micelles with a core of P blocks and different micellar shapes depending on block leng...

  13. Micellization and Dynamics of a Block Copolymer

    DEFF Research Database (Denmark)

    Hvidt, Søren

    2006-01-01

    Triblock copolymers of the type EPE, where E and P denote ethylene oxide and propylene oxide blocks, respectively, are industrially important copolymers often called Pluronics or Poloxamers. EPE copolymers form micelles with a core of P blocks and different micellar shapes depending on block length...

  14. New Considerations of Turbo Block Codes

    Institute of Scientific and Technical Information of China (English)

    YUEDianwu; EdSHWEDYK

    2004-01-01

    It is shown that (1) a general linear systematic block code can be expressed as a turbo block code and therefore can be decoded using any turbo decoding algorithm; (2) a turbo block code can be also encoded and decoded without any interleaver with the same performance as when an interleaver is present.

  15. A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-06-01

    Full Text Available Abstract Background The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV, however, possesses several mechanisms to evade complement-mediated lysis (CoML and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. Presentation of the hypothesis Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d-Fc, can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d-Fc proteins. As a control group, viruses

  16. HIV-2 infection: Where are we today?

    Directory of Open Access Journals (Sweden)

    Nayana A Ingole

    2013-01-01

    Full Text Available Context: The choice of antiretroviral therapy for HIV-2 differs from that for HIV-1, underscoring the importance of differentiating between the two. Aims: The current study was planned to find out the prevalence of HIV-2 infection at our center and to find out the utility of the current diagnostic algorithm in identifying the type of HIV infection. Setting and Design: Retrospective analysis in a tertiary care teaching institute over a period of three years. Materials and Methods: All patients diagnosed as HIV infected using NACO/WHO HIV testing strategy III were included in the study. They were classified as HIV-1 infected, HIV-2 infected and HIV-1 and HIV-2 co-infected based on their test results. For discordant samples, immunoblotting result from National Reference Laboratory was considered as final. Statistical Analysis Used: Comparison between HIV-1, HIV-2 and HIV-1+2 positive groups for age, gender, route of transmission was made using chi squared test. P value < 0.05 was considered as significant. Results: Of the total of 66,708 patients tested, 5,238 (7.9% were positive for HIV antibodies. 7.62%, 0.14%, 0.08% and 0.004% were HIV-1, HIV-2, HIV-1 and HIV-2 co-infected and HIV type indeterminate (HIV-1 Indeterminate, 2+ respectively. The current algorithm could not differentiate between the types of HIV infection (as HIV-1 or HIV-2 in 63 (1.2% cases. Conclusion: In areas like the Indian subcontinent, where epidemic of both HIV-1 and HIV-2 infections are ongoing, it is important to modify the current diagnostic algorithms to diagnose and confirm HIV-2 infections.

  17. Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.

    Directory of Open Access Journals (Sweden)

    Yanxing Han

    Full Text Available BACKGROUND: Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5alpha, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies. METHOD AND FINDINGS: In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons. CONCLUSIONS: These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s. Further characterization of this novel gene product(s will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1.

  18. Inhibition of HIV-1 gene expression by Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A

    Directory of Open Access Journals (Sweden)

    Saxena Deepti

    2009-10-01

    Full Text Available Abstract Background Eukaryotic translation initiation factor eIF5A has been implicated in HIV-1 replication. This protein contains the apparently unique amino acid hypusine that is formed by the post-translational modification of a lysine residue catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase (DOHH. DOHH activity is inhibited by two clinically used drugs, the topical fungicide ciclopirox and the systemic medicinal iron chelator deferiprone. Deferiprone has been reported to inhibit HIV-1 replication in tissue culture. Results Ciclopirox and deferiprone blocked HIV-1 replication in PBMCs. To examine the underlying mechanisms, we investigated the action of the drugs on eIF5A modification and HIV-1 gene expression in model systems. At early times after drug exposure, both drugs inhibited substrate binding to DOHH and prevented the formation of mature eIF5A. Viral gene expression from HIV-1 molecular clones was suppressed at the RNA level independently of all viral genes. The inhibition was specific for the viral promoter and occurred at the level of HIV-1 transcription initiation. Partial knockdown of eIF5A-1 by siRNA led to inhibition of HIV-1 gene expression that was non-additive with drug action. These data support the importance of eIF5A and hypusine formation in HIV-1 gene expression. Conclusion At clinically relevant concentrations, two widely used drugs blocked HIV-1 replication ex vivo. They specifically inhibited expression from the HIV-1 promoter at the level of transcription initiation. Both drugs interfered with the hydroxylation step in the hypusine modification of eIF5A. These results have profound implications for the potential therapeutic use of these drugs as antiretrovirals and for the development of optimized analogs.

  19. Inhibition of HIV-1 gene expression by Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A.

    Science.gov (United States)

    Hoque, Mainul; Hanauske-Abel, Hartmut M; Palumbo, Paul; Saxena, Deepti; D'Alliessi Gandolfi, Darlene; Park, Myung Hee; Pe'ery, Tsafi; Mathews, Michael B

    2009-10-13

    Eukaryotic translation initiation factor eIF5A has been implicated in HIV-1 replication. This protein contains the apparently unique amino acid hypusine that is formed by the post-translational modification of a lysine residue catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase (DOHH). DOHH activity is inhibited by two clinically used drugs, the topical fungicide ciclopirox and the systemic medicinal iron chelator deferiprone. Deferiprone has been reported to inhibit HIV-1 replication in tissue culture. Ciclopirox and deferiprone blocked HIV-1 replication in PBMCs. To examine the underlying mechanisms, we investigated the action of the drugs on eIF5A modification and HIV-1 gene expression in model systems. At early times after drug exposure, both drugs inhibited substrate binding to DOHH and prevented the formation of mature eIF5A. Viral gene expression from HIV-1 molecular clones was suppressed at the RNA level independently of all viral genes. The inhibition was specific for the viral promoter and occurred at the level of HIV-1 transcription initiation. Partial knockdown of eIF5A-1 by siRNA led to inhibition of HIV-1 gene expression that was non-additive with drug action. These data support the importance of eIF5A and hypusine formation in HIV-1 gene expression. At clinically relevant concentrations, two widely used drugs blocked HIV-1 replication ex vivo. They specifically inhibited expression from the HIV-1 promoter at the level of transcription initiation. Both drugs interfered with the hydroxylation step in the hypusine modification of eIF5A. These results have profound implications for the potential therapeutic use of these drugs as antiretrovirals and for the development of optimized analogs.

  20. Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

    DEFF Research Database (Denmark)

    Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

    2015-01-01

    into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block...... and the abdominal muscle-relaxing effect. RESULTS: The lateral part of the cutaneous sensory block area was a median of 266 cm2 (interquartile range, 191-310 cm2) and the medial part 76 cm 2(interquartile range, 54-127 cm2). In all the volunteers, lateral wall muscle thickness decreased significantly by 9.2 mm (6......BACKGROUND AND OBJECTIVES: The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. METHODS: Sixteen...

  1. Family physicians and HIV infection.

    Science.gov (United States)

    Hall, N; Crochette, N; Blanchi, S; Lavoix, A; Billaud, E; Baron, C; Abgueguen, P; Perré, P; Rabier, V

    2015-01-01

    We aimed to describe the current and desired involvement of family physicians (FPs) in the treatment of HIV patients (screening practices, potential training and patient follow-up) to reduce the duration and frequency of their hospital treatment. We conducted a descriptive cross-sectional survey between 2011 and 2012 with the support of COREVIH (Regional Coordinating Committee on HIV). We sent a self-assessment questionnaire to all FPs of the Pays de la Loire region to enquire about their HIV screening practices and expectations for the management of HIV patients. A total of 871 FPs completed the questionnaire (response rate: 30.4%). A total of 54.2% said to provide care to HIV patients; the mean number of HIV patients per FP was estimated at 1.4. With regard to HIV screening, 12.2% systematically suggest an HIV serology to their patients and 72.7% always suggest it to pregnant women. About 45.4% of responding FPs said to be willing to manage HIV patients (clinical and biological monitoring, compliance checks and prescription renewal). FPs mainly reported the lack of training and the low number of HIV patients as a barrier to their further involvement in the management of HIV patients. The responding FPs provide care to very few HIV patients. They are, however, willing to be more involved in the routine care of these patients. Medical training provided by COREVIH would help improve HIV screening. The management of HIV patients could thus be handed over to willing FPs. Copyright © 2015. Published by Elsevier SAS.

  2. The role of culture in effective HIV/AIDS communication by theatre in South Africa.

    Science.gov (United States)

    Uwah, Chijioke

    2013-01-01

    The need to effectively communicate HIV/AIDS messages in South Africa, given the high prevalence of the pandemic, cannot be overemphasised. Communication scholars have long emphasised the need to recognise adherence to cultural norms of target communities as catalyst for effective HIV/AIDS communication. Unfortunately this call has not been totally heeded by the designers of HIV/AIDS communication instruments. In the case of theatre, research has shown that in South Africa, theatre groups have gone into communities with pre-packaged plays without due cognisance of the cultural norms and beliefs of the target population. This research was conducted in KwaZulu-Natal (the province with the highest prevalence rate of HIV/AIDS infection in South Africa). Using a qualitative research methodology this paper investigated the inclusion/non-inclusion of the cultural norms of the target population in the design of the dramatic performance by the theatre group in its HIV/AIDS campaigns. The findings indicate that while the group did try to incorporate aspects of the cultural norms of the target population, it did so at a level that failed to effectively communicate the HIV/AIDS message to its audiences. This paper therefore seeks to show through empirical evidence that the non-inclusion of cultural norms and values of the target population has acted as a stumbling block in the effective communication of HIV/AIDS messages by theatre groups in the country.

  3. Host factors and HIV-1 replication: clinical evidence and potential therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Mariana eSanta-Marta

    2013-10-01

    Full Text Available HIV and human defense mechanisms have co-evolved to counteract each other. In the process of infection, HIV takes advantage of cellular machinery and blocks the action of the host restriction factors. A small subset of HIV+ individuals control HIV infection and progression to AIDS in the absence of treatment. These individuals known, as long-term non-progressors (LNTPs exhibit genetic and immunological characteristics that confer upon them an efficient resistance to infection and/or disease progression. The identification of some of these host factors led to the development of therapeutic approaches that attempted to mimic the natural control of HIV infection. Some of these approaches are currently being tested in clinical trials. While there are many genes which carry mutations and polymorphisms associated with non-progression, this review will be specifically focused on HIV host restriction factors (RF including both the main chemokine receptors and chemokines as well as intracellular restriction factors including, APOBEC, TRIM, tetherin and SAMHD1. The understanding of molecular profiles and mechanisms present in LTNPs should provide new insights to control HIV infection and contribute to the development of novel therapies against AIDS.

  4. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  5. Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

    Science.gov (United States)

    Ceña-Diez, Rafael; García-Broncano, Pilar; de la Mata, Francisco Javier; Gómez, Rafael; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection. PMID:27313457

  6. Inhibition of HIV type 1 infection with a RANTES-IgG3 fusion protein.

    Science.gov (United States)

    Challita-Eid, P M; Klimatcheva, E; Day, B T; Evans, T; Dreyer, K; Rimel, B J; Rosenblatt, J D; Planelles, V

    1998-12-20

    The natural ligands for the chemokine receptors CCR5 (RANTES, MIP-1alpha, and MIP-1beta) and CXCR4 (SDF-1) can act as potent inhibitors of infection by the human immunodeficiency virus type 1 (HIV-1) at the level of viral entry. Unlike antibody-mediated inhibition, chemokine-mediated inhibition is broadly effective. Different HIV-1 strains can utilize the same coreceptor(s) for viral entry and, therefore, can be blocked by the same chemokine(s). HIV-1 strains that are highly resistant to neutralization by V3-specific antibodies are sensitive to inhibition by chemokines. Therefore, the use of chemokine-derived molecules constitutes a potential therapeutic approach to prevent infection by HIV-1. We have generated a fusion protein between RANTES and human IgG3 (RANTES-IgG3). The effectiveness of RANTES-IgG3 inhibition of infection by HIV-1 was similar to that of rRANTES. Inhibition of HIV-1 by RANTES-IgG3 was specific for CCR5-dependent but not CXCR4-dependent HIV-1 isolates. Fusion of a chemokine to an IgG moiety offers two desirable properties with respect to the recombinant chemokine alone. First, IgG fusion proteins have extended half-lives in vivo. Second, molecules with IgG heavy chain moieties may be able to cross the placenta and potentially induce fetal protection.

  7. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

    Science.gov (United States)

    Briz, Verónica; Sepúlveda-Crespo, Daniel; Diniz, Ana Rita; Borrego, Pedro; Rodes, Berta; de La Mata, Francisco Javier; Gómez, Rafael; Taveira, Nuno; Muñoz-Fernández, Mª Ángeles

    2015-08-01

    The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

  8. Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk

    Science.gov (United States)

    Fouda, Genevieve G.; Jaeger, Frederick H.; Amos, Joshua D.; Ho, Carrie; Kunz, Erika L.; Anasti, Kara; Stamper, Lisa W.; Liebl, Brooke E.; Barbas, Kimberly H.; Ohashi, Tomoo; Moseley, Martin Arthur; Liao, Hua-Xin; Erickson, Harold P.; Alam, S. Munir; Permar, Sallie R.

    2013-01-01

    Achieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can reduce postnatal HIV-1 transmission, yet toxicities and the development of drug-resistant viral strains may limit the effectiveness of this strategy. Interestingly, in the absence of antiretroviral prophylaxis, greater than 90% of infants exposed to HIV-1 via breastfeeding remain uninfected, despite daily mucosal exposure to the virus for up to 2 y. Moreover, milk of uninfected women inherently neutralizes HIV-1 and prevents virus transmission in animal models, yet the factor(s) responsible for this anti-HIV activity is not well-defined. In this report, we identify a primary HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing, yet its antimicrobial properties have not previously been established. Purified TNC captured and neutralized multiclade chronic and transmitted/founder HIV-1 variants, and depletion of TNC abolished the HIV-1–neutralizing activity of milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. Our results demonstrate the ability of an innate mucosal host protein found in milk to neutralize HIV-1 via binding to the chemokine coreceptor site, potentially explaining why the majority of HIV-1–exposed breastfed infants are protected against mucosal HIV-1 transmission. PMID:24145401

  9. Seismicity of the Jalisco Block

    Science.gov (United States)

    Nunez-Cornu, F. J.; Rutz, M.; Camarena-Garcia, M.; Trejo-Gomez, E.; Reyes-Davila, G.; Suarez-Plascencia, C.

    2002-12-01

    In April 2002 began to transmit the stations of the first phase of Jalisco Telemetric Network located at the northwest of Jalisco Block and at the area of Volcan de Fuego (Colima Volcano), in June were deployed four additional MarsLite portable stations in the Bahia de Banderas area, and by the end of August one more portable station at Ceboruco Volcano. The data of these stations jointly with the data from RESCO (Colima Telemetric Network) give us the minimum seismic stations coverage to initiate in a systematic and permanent way the study of the seismicity in this very complex tectonic region. A preliminary analysis of seismicity based on the events registered by the networks using a shutter algorithm, confirms several important features proposed by microseismicity studies carried out between 1996 and 1998. A high level of seismicity inside and below of Rivera plate is observed, this fact suggest a very complex stress pattern acting on this plate. Shallow seismicity at south and east of Bahia de Banderas also suggest a complex stress pattern in this region of the Jalisco Block, events at more than 30 km depth are located under the mouth of the bay and in face of it, a feature denominated Banderas Boundary mark the change of the seismic regime at north of this latitude (20.75°N), however some shallow events were located at the region of Nayarit.

  10. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    HIV Treatment What to Start: Choosing an HIV Regimen (Last updated 2/24/2016; last reviewed 2/24/ ... of HIV medicines used to treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with ...

  11. Isostatic compression of buffer blocks. Middle scale

    Energy Technology Data Exchange (ETDEWEB)

    Ritola, J.; Pyy, E. [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-01-15

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  12. Evolution of the health sector response to HIV in Myanmar: progress, challenges and the way forward.

    Science.gov (United States)

    Oo, Htun Nyunt; Hone, San; Fujita, Masami; Maw-Naing, Amaya; Boonto, Krittayawan; Jacobs, Marjolein; Phyu, Sabe; Bollen, Phavady; Cheung, Jacquie; Aung, Htin; Aung Sang, May Thu; Myat Soe, Aye; Pendse, Razia; Murphy, Eamonn

    2016-11-28

    Critical building blocks for the response to HIV were made until 2012 despite a series of political, social and financial challenges. A rapid increase of HIV service coverage was observed from 2012 to 2015 through collaborative efforts of government and non-governmental organisations (NGOs). Government facilities, in particular, demonstrated their capacity to expand services for antiretroviral therapy (ART), prevention of mother-to-child transmission (PMTCT) of HIV, tuberculosis and HIV co-infection and methadone-maintenance therapy (MMT). After nearly three decades into the response to HIV, Myanmar has adopted strategies to provide the right interventions to the right people in the right places to maximise impact and cost efficiency. In particular, the country is now using strategic information to classify areas into high-, medium- and low-HIV burden and risk of new infections for geographical prioritisation - as HIV remains concentrated among key population (KP) groups in specific geographical areas. Ways forward include: •Addressing structural barriers for KP to access services, and identifying and targeting KPs at higher risk;•Strengthening the network of public facilities, NGOs and general practitioners and introducing a case management approach to assist KPs and other clients with unknown HIV status, HIV-negative clients and newly diagnosed clients to access the health services across the continuum to increase the number of people testing for HIV and to reduce loss to follow-up in both prevention and treatment;•Increasing the availability of HIV testing and counselling services for KPs, clients of female sex workers (FSW), and other populations at risk, and raising the demand for timely testing including expansion of outreach and client-initiated voluntary counselling and testing (VCT) services;•Monitoring and maximising retention from HIV diagnosis to ART initiation and expanding quality HIV laboratory services, especially viral load

  13. Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma: Implications for Immunotherapy.

    Science.gov (United States)

    Yanik, Elizabeth L; Kaunitz, Genevieve J; Cottrell, Tricia R; Succaria, Farah; McMiller, Tracee L; Ascierto, Maria L; Esandrio, Jessica; Xu, Haiying; Ogurtsova, Aleksandra; Cornish, Toby; Lipson, Evan J; Topalian, Suzanne L; Engels, Eric A; Taube, Janis M

    2017-07-01

    The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients. To compare the local tumor immune microenvironment (TME) in anal SCCs from HIV-positive and HIV-negative patients. Anal SCC tumor specimens derived from the AIDS and Cancer Specimen Resource (National Cancer Institute) and Johns Hopkins Hospital included specimens. Tumors were subjected to immunohistochemical analysis for immune checkpoints (PD-L1, PD-1, LAG-3) and immune cell (IC) subsets (CD3, CD4, CD8, CD68). Expression profiling for immune-related genes was performed on select HIV-positive and HIV-negative cases in PD-L1+ tumor areas associated with ICs. Programmed death-ligand 1 expression on tumor cells and ICs, PD-L1 patterns (adaptive vs constitutive), degree of IC infiltration, quantified densities of IC subsets, and gene expression profiles in anal SCCs from HIV-positive vs HIV-negative patients. Approximately half of 40 tumor specimens from 23 HIV-positive and 17 HIV-negative patients (29 men and 11 women; mean [SD] age, 51 [9.9] years) demonstrated tumor cell PD-L1 expression, regardless of HIV status. Median IC densities were not significantly decreased in HIV-associated tumors for any cellular subset studied. Both adaptive (IC-associated) and constitutive PD-L1 expression patterns were observed. Immune cell PD-L1 expression correlated with increasing intensity of IC infiltration (r = 0.52; 95% CI, 0.26-0.78; P anal SCCs (fold change, 12.69; P anal SCC. These findings demonstrate an immune

  14. System Synthesis for Networks of Programmable Blocks

    CERN Document Server

    Mannion, Ryan; Cotterell, Susan; Vahid, Frank

    2011-01-01

    The advent of sensor networks presents untapped opportunities for synthesis. We examine the problem of synthesis of behavioral specifications into networks of programmable sensor blocks. The particular behavioral specification we consider is an intuitive user-created network diagram of sensor blocks, each block having a pre-defined combinational or sequential behavior. We synthesize this specification to a new network that utilizes a minimum number of programmable blocks in place of the pre-defined blocks, thus reducing network size and hence network cost and power. We focus on the main task of this synthesis problem, namely partitioning pre-defined blocks onto a minimum number of programmable blocks, introducing the efficient but effective PareDown decomposition algorithm for the task. We describe the synthesis and simulation tools we developed. We provide results showing excellent network size reductions through such synthesis, and significant speedups of our algorithm over exhaustive search while obtaining...

  15. HIV and childhood cancer

    African Journals Online (AJOL)

    risk declines to 76 per 100 000 per annum in children on ART,6 demonstrating ... His clinical focus is HIV-related malignancy, brain tumours and bone marrow transplantation. His current ... metastases and an abdominal ultrasound to look for ...

  16. HIV Excess Cancers JNCI

    Science.gov (United States)

    In 2010, an estimated 7,760 new cancers were diagnosed among the nearly 900,000 Americans known to be living with HIV infection. According to the first comprehensive study in the United States, approximately half of these cancers were in excess of what wo

  17. HIV Associated Sensory Neuropathy

    OpenAIRE

    G, Amruth; S, Praveen-kumar; B, Nataraju; BS, Nagaraja

    2014-01-01

    Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities.

  18. Modeling HIV Cure

    Science.gov (United States)

    Perelson, Alan; Conway, Jessica; Cao, Youfang

    A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of post-treatment control (PTC) or ``functional cure'' of HIV-infection. Some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection such that the amount of virus in the circulation is maintained undetectable by clinical assays for years. The model explains PTC occurring in some patients by having a parameter regime in which the model exhibits bistability, with both a low and high steady state viral load being stable. The model makes a number of predictions about how to attain the low PTC steady state. Bistability in this model depends upon the immune response becoming exhausted when over stimulated. I will also present a generalization of the model in which immunotherapy can be used to reverse immune exhaustion and compare model predictions with experiments in SIV infected macaques given immunotherapy and then taken off of antiretroviral therapy. Lastly, if time permits, I will discuss one of the hurdles to true HIV eradication, latently infected cells, and present clinical trial data and a new model addressing pharmacological means of flushing out the latent reservoir. Supported by NIH Grants AI028433 and OD011095.

  19. [HIV infection and immigration].

    Science.gov (United States)

    Monge, Susana; Pérez-Molina, José A

    2016-01-01

    Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. to prevent hiv infection

    African Journals Online (AJOL)

    2008-10-14

    Oct 14, 2008 ... about other things. ‡ ... deliberately trying to forget the entire experience. .... pleasant nor easy, and almost all of the rape survivors .... make it easier to treat HIV/AIDS in adults, but development of simplified drugs for children ...

  1. Poverty, sex and HIV.

    Science.gov (United States)

    Nattrass, Nicoli

    2009-10-01

    There is an ongoing debate about the relative importance of economic factors (notably poverty) and sexual behavior in driving the AIDS epidemic. This paper draws on relevant research and cross-country regression analysis to argue that the impact of economic determinants is dwarfed by contextual factors within Africa. The regression analysis suggests that controlling for per capita income, calories per capita and the ratio of female to male participation rates (none of which were statistically significant): being a Southern African country increases expected HIV prevalence 8.3 times; being in the rest of Sub-Saharan Africa 3 times; being a predominantly Protestant country 2.5 times; and being a predominantly Muslim country reduces expected HIV prevalence to 62% of the base case. Including the share of income going to the poor did not improve the model and was itself statistically insignificant. The analysis suggests that poverty may play a role in the HIV epidemic in some countries (and may well be a factor affecting the vulnerability of some people to HIV infection in all countries) but that its overall impact is dwarfed by social and behavioral factors.

  2. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    Jun 15, 2007 ... necessary tests are done initially and the correct treatment started. Knowledge of megakaryocyte ... such as hepatitis B and C is increasing within the HIV-infected community and can ... HI virus and Staphylococcus aureus – perhaps another reason why ... directed against the Fc portion of IgG antibodies as ...

  3. HIV / AIDS: Symptoms, Diagnosis, Prevention and Treatment

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: Symptoms , Diagnosis, Prevention and Treatment Past Issues / ... Most people who have become recently infected with HIV will not have any symptoms. They may, however, ...

  4. Dental caries in HIV-seropositive women.

    Science.gov (United States)

    Phelan, J A; Mulligan, R; Nelson, E; Brunelle, J; Alves, M E A F; Navazesh, M; Greenspan, D

    2004-11-01

    Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

  5. General Floorplans with L/T-Shaped Blocks Using Corner Block List

    Institute of Scientific and Technical Information of China (English)

    Yu-Chun Ma; Xian-Long Hong; She-Qin Dong; C.K.Cheng; Jun Gu

    2006-01-01

    With the recent advent of deep submicron technology and new packing schemes, the components in the integrated circuit are often not rectangular. On the basis of the representation of Corner Block List (CBL), we propose a new method of handling rectilinear blocks. In this paper, the handling of the rectilinear blocks is simplified by transforming the L/T-shaped block problem into the align-abutment constraint problem. We devise the block rejoining process and block alignment operation for forming the L/T-shaped blocks into their original configurations. The shape flexibility of the soft blocks, and the rotation and reflection of L/T-shaped blocks are exploited to obtain a tight packing. The empty rooms are introduced to the process of block rejoining. The efficiency and effectiveness of the proposed method are demonstrated by the experimental results on a set of some benchmark examples.

  6. Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

    Science.gov (United States)

    Vacas-Córdoba, Enrique; Maly, Marek; De la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection. PMID:27103798

  7. HIV Sequence Compendium 2010

    Energy Technology Data Exchange (ETDEWEB)

    Kuiken, Carla [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Foley, Brian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leitner, Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Apetrei, Christian [Univ. of Pittsburgh, PA (United States); Hahn, Beatrice [Univ. of Alabama, Tuscaloosa, AL (United States); Mizrachi, Ilene [National Center for Biotechnology Information, Bethesda, MD (United States); Mullins, James [Univ. of Washington, Seattle, WA (United States); Rambaut, Andrew [Univ. of Edinburgh, Scotland (United Kingdom); Wolinsky, Steven [Northwestern Univ., Evanston, IL (United States); Korber, Bette [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2010-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  8. [Ultrasound for peripheral neural block].

    Science.gov (United States)

    Kefalianakis, F

    2005-03-01

    Ultrasound is well established in medicine. Unfortunately, ultrasound is still rarely used in the area of anesthesia. The purpose of the article is to illustrate the possibilities and limitations of ultrasound in regional anesthesia. The basic principles of ultrasound are the piezoelectric effect and the behaviour of acoustic waveforms in human tissue. Ultrasound imaging in medicine uses high frequency pulses of sound waves (2.5-10 MHz). The following images are built up from the reflected sounds. The ultrasound devices used in regional anesthesia (commonly by 10 MHz) deliver a two-dimensional view. The main step for a successful regional anaesthesia is to identify the exact position of the nerve. In addition, specific surface landmarks and the use of peripheral nerve stimulator help to detect the correct position of the needle. Nerves are demonstrated as an composition of hyperechogenic (white) and hypoechogenic (black) areas. The surrounding hyperechogenic parts are epi- and perineurium, the dark hypoechogenic part is the neural tissue. The composition of peripheral nerves are always similar, but the quantities of each part, of surrounding perineurium and nerval structures, differ. Further the imaging of nerves is significantly influenced by the angle of beam to the nerve and the surrounding anatomic structures. Only experience and correct interpretation make the ultrasound a valid method in clinical practice. Correct interpretation has to be learned by standardized education. Three examples of peripheral nerve blocks are described. The detection of nerves and the visualization of the correct spread of local anesthetics to the nerves are the main principles of effective ultrasound-guided regional anesthesia, whereas closest proximity of the needle to the target nerve is not necessary. The described examples of ultrasound guidance for nerval block illustrates the specific procedures with reduced probability of nerval irritation, high success and low rate of

  9. Newly synthesized APOBEC3G is incorporated into HIV virions, inhibited by HIV RNA, and subsequently activated by RNase H.

    Directory of Open Access Journals (Sweden)

    Vanessa B Soros

    2007-02-01

    Full Text Available APOBEC3G (A3G is a potent antiretroviral deoxycytidine deaminase that, when incorporated into HIV virions, hypermutates nascent viral DNA formed during reverse transcription. HIV Vif counters the effect of A3G by depleting intracellular stores of the enzyme, thereby blocking its virion incorporation. Through pulse-chase analyses, we demonstrate that virion A3G is mainly recruited from the cellular pool of newly synthesized enzyme compared to older "mature" A3G already residing in high-molecular-mass RNA-protein complexes. Virion-incorporated A3G forms a large complex with viral genomic RNA that is clearly distinct from cellular HMM A3G complexes, as revealed by both gel filtration and biochemical fractionation. Unexpectedly, the enzymatic activity of virion-incorporated A3G is lost upon its stable association with HIV RNA. The activity of the latent A3G enzyme is ultimately restored during reverse transcription by the action of HIV RNase H. Degradation of the viral genomic RNA by RNase H not only generates the minus-strand DNA substrate targeted by A3G for hypermutation but also removes the inhibitory RNA bound to A3G, thereby enabling its function as a deoxycytidine deaminase. These findings highlight an unexpected interplay between host and virus where initiation of antiviral enzymatic activity is dependent on the action of an essential viral enzyme.

  10. Understanding the drivers of interprofessional collaborative practice among HIV primary care providers and case managers in HIV care programmes.

    Science.gov (United States)

    Mavronicolas, Heather A; Laraque, Fabienne; Shankar, Arti; Campbell, Claudia

    2017-05-01

    Care coordination programmes are an important aspect of HIV management whose success depends largely on HIV primary care provider (PCP) and case manager collaboration. Factors influencing collaboration among HIV PCPs and case managers remain to be studied. The study objective was to test an existing theoretical model of interprofessional collaborative practice and determine which factors play the most important role in facilitating collaboration. A self-administered, anonymous mail survey was sent to HIV PCPs and case managers in New York City. An adapted survey instrument elicited information on demographic, contextual, and perceived social exchange (trustworthiness, role specification, and relationship initiation) characteristics. The dependent variable, perceived interprofessional practice, was constructed from a validated scale. A sequential block wise regression model specifying variable entry order examined the relative importance of each group of factors and of individual variables. The analysis showed that social exchange factors were the dominant drivers of collaboration. Relationship initiation was the most important predictor of interprofessional collaboration. Additional influential factors included organisational leadership support of collaboration, practice settings, and frequency of interprofessional meetings. Addressing factors influencing collaboration among providers will help public health programmes optimally design their structural, hiring, and training strategies to foster effective social exchanges and promote collaborative working relationships.

  11. HIV-positive people, HIV-negative partners.

    Science.gov (United States)

    Harmon, L; Volker, M

    1995-01-01

    More relationships exist today between HIV-positive and HIV-negative partners. This article explores the underlying dynamics that might account for this phenomenon. Codependency theories may explain these relationships for some couples. For other couples, it is suggested that positive-negative homosexual relationships may be influenced by both unhealthy and healthy gay developmental experiences as well as by a sense of compassion. The article addresses both HIV-positive people choosing HIV-negative partners and vice versa. Treatment issues for the various theories are discussed and recommendations are made.

  12. Diagnostik af HIV-1 infektionen

    DEFF Research Database (Denmark)

    Christiansen, C B; Dickmeiss, E; Bygbjerg, Ib Christian

    1991-01-01

    Different methods have been developed for the diagnosis of HIV infection, i.e. detection of antibodies, antigen and proviral DNA. ELISA methods for detecting HIV-1 antibodies are widely used as screening assays. A sample which is repeatedly positive with ELISA is re-tested with a confirmatory test....... For research purposes, detection of small amounts of proviral DNA can be made with polymerase chain reaction (PCR). The method is not yet applicable in routine diagnosis of HIV infection......., e.g. western blot. Antibodies to HIV-1 are not detectable until 2-3 months after infection, but antigens may be detectable during the last weeks of this initial period, though they disappear with the appearance of the antibodies. In the later stages of HIV infection, HIV antigen is again detectable...

  13. HIV and homosexuality in Pakistan.

    Science.gov (United States)

    Rajabali, Alefiyah; Khan, Saeed; Warraich, Haider J; Khanani, Mohammad R; Ali, Syed H

    2008-08-01

    In Pakistan, seven times more men are reported to be infected with HIV than women. Among the Pakistani population, modes of HIV transmission include infection through sexual contact, contaminated blood and blood products, injecting drug use, and mother-to-child transmission. Although most sexual transmission of HIV results from unsafe heterosexual contact, homosexual and bisexual contact also represent important modes of transmission. According to unpublished reports, the prevalence of HIV among homosexual and bisexual Pakistani men is reaching alarming proportions. We describe the Pakistani homosexual and bisexual culture, review statistics regarding HIV prevalence and risk behaviour, and identify areas of improvement in the HIV policy with specific focus on men who have sex with men.

  14. Cellular restriction factors affecting the early stages of HIV replication.

    Science.gov (United States)

    Perez, Omar; Hope, Thomas J

    2006-02-01

    Several innate immune mechanisms exist in mammalian cells that prevent the replication of viruses. These cellular factors influence the tropism of retroviruses in mammalian cells by inducing a dominant restriction that acts after viral entry but before integration into the host genome. The identification of several cellular factors involved with the post entry block of HIV has recently been revealed. These recent advances identified the tripartite motif protein 5alpha (Trim5alpha) and the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G), which work to inactivate several retroviruses including HIV-1. The mechanism of restriction by these cellular proteins is unknown. Therefore, this review highlights recent advances in understanding the function of Trim5alpha and APOBEC3G.

  15. Completeness of HIV reporting on death certificates for Floridians reported with HIV infection, 2000-2011

    OpenAIRE

    Trepka, Mary Jo; Diana M. Sheehan; Fennie, Kristopher P.; Niyonsenga, Theophile; Lieb, Spencer; Maddox, Lorene

    2015-01-01

    HIV mortality is used as a key measure to monitor the impact of HIV throughout the world. It is important that HIV be correctly recorded on death certificates so that the burden of HIV mortality can be tracked accurately. The objective of this study was to determine the extent of failure to correctly report HIV on death certificates and examine patterns of incompleteness by demographic factors. Causes of death on death certificates of people infected with HIV reported to the Florida HIV surve...

  16. Implications of prioritizing HIV cure: new momentum to overcome old challenges in HIV

    OpenAIRE

    Tucker, JD; Gilbertson, A; Lo, YR; Vitória, M

    2016-01-01

    Background Curing HIV is a new strategic priority for several major AIDS organizations. In step with this new priority, HIV cure research and related programs are advancing in low, middle, and high-income country settings. This HIV cure momentum may influence existing HIV programs and research priorities. Discussion Despite the early stage of ongoing HIV cure efforts, these changes have directly influenced HIV research funding priorities, pilot programs, and HIV messaging. The building moment...

  17. Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

    Directory of Open Access Journals (Sweden)

    Mingshun Zhang

    Full Text Available Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

  18. US youths in the early stages of HIV disease have low intakes of some micronutrients important for optimal immune function.

    Science.gov (United States)

    Kruzich, Laurie A; Marquis, Grace S; Carriquiry, Alicia L; Wilson, Craig M; Stephensen, Charles B

    2004-07-01

    We examined the association between micronutrient intakes and human immunodeficiency virus (HIV) infection in youths who were at increased nutritional risk because of the demands of growth and disease as well as poor dietary habits. This was a cross-sectional study to collect dietary intake data using the Block Food Frequency Questionnaire (98.2). Anthropometric, biochemical, clinical, and sociodemographic data were available.Subjects/Setting Participants included 264 HIV-infected and 127 HIV-uninfected adolescents and young adults from the Reaching for Excellence in Adolescent Care and Health network, a multisite observational study on HIV progression. Statistical analyses CD4(+) T cells were stratified for HIV-infected youths: >/=500, 200 to 499, and /=500 cells/microL. After controlling for other factors, HIV-infected participants with CD4(+) T cells >/=500 had decreased iron intake (P<.05) and tended to be associated with lower intakes of vitamins C and E (P<.10) compared with those with more advanced disease and HIV-uninfected youths. Among those youths with CD4(+) T cells between 200 and 499 cells/microL, a high anxiety score was associated with a sixfold increase in vitamin A intake as compared with those with a low score.Applications/conclusions Given the increased micronutrient requirements, nutrition counseling with HIV-infected youths should focus on early increase of intake of foods rich in micronutrients to improve growth, slow disease progression, and increase survival.

  19. XTT formazan widely used to detect cell viability inhibits HIV type 1 infection in vitro by targeting gp41.

    Science.gov (United States)

    Zhao, Qian; Ernst, Justin T; Hamilton, Andrew D; Debnath, Asim K; Jiang, Shibo

    2002-09-20

    XTT can be metabolically reduced by mitochondrial dehydrogenase in viable cells to a water-soluble formazan product. Thus XTT has been widely used to evaluate cell viability and to screen anti-HIV agents and the cytotoxicity of these agents. The present studies demonstrated that XTT formazan derived from XTT in cell culture significantly inhibits the fusion of HIV-1-infected cells with uninfected cells. Synthetic XTT formazan effectively inhibited the replication of laboratory-adapted and primary HIV-1 isolates and cell-to-cell fusion with low cytotoxicity. It blocks the six-helix bundle formation between peptides derived from the N- and C-terminal heptad repeat regions of the gp41 ectodomain (designated N- and C-peptides, respectively). Analysis by a computer-aided docking program indicates that XTT formazan may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil of gp41. These results suggest that XTT formazan inhibits HIV-1 entry by targeting the alpha-helical coiled-coil domain of gp41. This small molecular nonpeptide antiviral compound can be used as a lead for designing more effective HIV-1 entry inhibitors targeting the fusion stage of HIV-1 infection. But because XTT formazan itself has anti-HIV-1 activity, caution should be exercised when XTT is used to evaluate HIV-1 infectivity.

  20. Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu

    Science.gov (United States)

    Varthakavi, Vasundhara; Heimann-Nichols, Ellen; Smith, Rita M; Sun, Yuehui; Bram, Richard J; Ali, Showkat; Rose, Jeremy; Ding, Lingmei; Spearman, Paul

    2008-01-01

    The HIV-1 Vpu protein is required for efficient viral release from human cells. For HIV-2, the envelope (Env) protein replaces the role of Vpu. Both Vpu and HIV-2 Env enhance virus release by counteracting an innate host-cell block within human cells that is absent in African green monkey (AGM) cells. Here we identify calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting host factor that restricts HIV-1 release. Expression of human CAML (encoded by CAMLG) in AGM cells conferred a strong restriction of virus release that was reversed by Vpu and HIV-2 Env, suggesting that CAML is the mechanistic link between these two viral regulators. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 and murine leukemia virus release. These results point to CAML as a Vpu-sensitive host restriction factor that inhibits HIV release from human cells. The ability of CAML to inhibit virus release should illuminate new therapeutic strategies against HIV. PMID:18500349

  1. Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection.

    Science.gov (United States)

    Goh, Yun Shan; Necchi, Francesca; O'Shaughnessy, Colette M; Micoli, Francesca; Gavini, Massimiliano; Young, Stephen P; Msefula, Chisomo L; Gondwe, Esther N; Mandala, Wilson L; Gordon, Melita A; Saul, Allan J; MacLennan, Calman A

    2016-04-01

    Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS) antibodies in some HIV-infected African adults block this killing. The objective was to understand how these high levels of anti-LPS antibodies interfere with the killing of Salmonella. Sera and affinity-purified antibodies from African HIV-infected adults that failed to kill invasive S. Typhimurium D23580 were compared to sera from HIV-uninfected and HIV-infected subjects with bactericidal activity. The failure of sera from certain HIV-infected subjects to kill Salmonella was found to be due to an inherent inhibitory effect of anti-LPS antibodies. This inhibition was concentration-dependent and strongly associated with IgA and IgG2 anti-LPS antibodies (peffect of high concentrations of anti-LPS antibodies is seen with IgM as well as IgG and IgA. No correlation was found between affinity or avidity, or complement deposition or consumption, and inhibition of killing. IgG and IgM classes of anti-S. Typhimurium LPS antibodies from HIV-infected and HIV-uninfected individuals are bactericidal, while at very high concentrations, anti-LPS antibodies of all classes inhibit in vitro killing of Salmonella. This could be due to a variety of mechanisms relating to the poor ability of IgA and IgG2 to activate complement, and deposition of complement at sites where it cannot insert in the bacterial membrane. Vaccine trials are required to understand the significance of lack of in vitro killing by anti-LPS antibodies from a minority of HIV-infected individuals with impaired immune homeostasis.

  2. Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2002-11-01

    Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.

  3. Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

    Directory of Open Access Journals (Sweden)

    Ceña-Diez R

    2016-05-01

    Full Text Available Rafael Ceña-Diez,1–4,* Pilar García-Broncano,1–5,* Francisco Javier de la Mata,4,6 Rafael Gómez,4,6 Mª Ángeles Muñoz-Fernández1–4 1Hospital General Universitario Gregorio Marañon, 2Instituto de Investigación Sanitaria Gregorio Marañon, 3Spanish HIV HGM Biobank, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, 5Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, 6Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain *These authors contributed equally to this work Abstract: The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection. Keywords: G2-S16, dendrimer, HIV-1, SEVI, microbicide, antiretrovirals

  4. Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

    Energy Technology Data Exchange (ETDEWEB)

    McClure, Janela [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Margineantu, Daciana H. [Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Sweet, Ian R. [Department of Medicine (Division of Metabolism, Endocrinology, and Nutrition), University of Washington, Seattle, WA (United States); Polyak, Stephen J., E-mail: polyak@uw.edu [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Department of Global Health, University of Washington, Seattle, WA (United States)

    2014-01-20

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases.

  5. Encephalitis in primary HIV infection

    DEFF Research Database (Denmark)

    Helleberg, M; Kirk, O

    2013-01-01

    We report a case of primary HIV encephalitis, which initially presented as acute psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis and multiple infarctions, whereas a brain biopsy after six weeks of symptoms showed HIV encephalitis with microglial nodules, but no signs...... of vasculitis. We review previous reported cases and radiological findings in HIV encephalitis and discuss the role of antiretroviral therapy and steroids in its management....

  6. HIV: Social and Environmental Factors

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses how social and environmental factors may put African Americans at greater risk for HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  7. National HIV/AIDS Strategy

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about the importance of the National HIV/AIDS Strategy and the work of CDC.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  8. Progression of HIV in haemophilia.

    Science.gov (United States)

    Ragni, M V

    1998-07-01

    The recent elucidation of the life cycle and dynamics of the human immunodeficiency virus (HIV) and technological advances in development of the HIV RNA PCR assay for sensitive detection of viral load have revolutionized the diagnosis, management, and treatment of HIV infection. Beginning with initial infection, there is unremitting, high-level viral replication that persists throughout the course of HIV infection. The measure of the amount of virus present in plasma, HIV viral load, is the single most important predictor of HIV progression, the best indicator of immune system decline, and the best guide for initiating and monitoring antiviral treatment. Further, HIV viral load has become the new yardstick against which other markers, including CD4 number, age, chemokine receptor mutations, cytotoxic T-cell responses, and neutralizing antibody titers are assessed. For individuals with haemophilia, additional 'markers' may have significant impact on the outcome of HIV disease. Chronic factor concentrate treatment has led to transfusion-associated hepatitis, co-infection with hepatitis C (HCV), and chronic liver disease. The latter may become accelerated with HIV progression and may lead to hepatotoxicity with antiviral drug therapy. Chronic factor concentrate treatment has also been associated with immunosuppression, including both B- and T-cell immune defects. In HIV(+) haemophilic men, this immune deficit has led to lower CD4 counts with HIV progression and poorer CD4 response to antiviral drugs than in gay men. The underlying haemophilic bleeding tendency may result in significant haemorrhage with HIV-associated immune thrombocytopenia and with protease inhibitor antiretroviral therapy. Although AIDS is the leading cause of death in this group, the reduction in the size of the haemophilia population over the next two centuries is estimated to be small, and survival should improve as better antiviral therapeutics are identified.

  9. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Anthony M. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Cheung, Pamela [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Swartz, Talia H.; Li, Hongru [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Tsibane, Tshidi [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Durham, Natasha D. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Basler, Christopher F. [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Felsenfeld, Dan P. [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Chen, Benjamin K., E-mail: benjamin.chen@mssm.edu [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States)

    2016-03-15

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.

  10. Transcytosis of HIV-1 through vaginal epithelial cells is dependent on trafficking to the endocytic recycling pathway.

    Directory of Open Access Journals (Sweden)

    Ballington L Kinlock

    Full Text Available BACKGROUND: While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. CONCLUSIONS/SIGNIFICANCE: Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.

  11. HIV and chronic kidney disease.

    Science.gov (United States)

    Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV

  12. Body Shape Changes with HIV

    Science.gov (United States)

    ... Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home Guidelines Integrated ...

  13. Diet and Nutrition and HIV

    Science.gov (United States)

    ... Policies and Reports Provider Education Provider Education Home HIV Meds Updates Online Courses (CME) Case Studies Journal Articles Glossary Quick References Quick References Home Guidelines Integrated ...

  14. Efficient Distribution of Triggered Synchronous Block Diagrams

    Science.gov (United States)

    2011-10-21

    called a trigger. At a given synchronous step, if the trigger is true , the block fires normally; otherwise, the block stutters , that is, keeps its...outputs have the same value as in the previous step, but they are still transmitted to downstream blocks. In this paper we present an implementation...optimizations that apply to general Triggered SBDs, we also present further optimizations for the case of Timed SBDs. 1.1 Motivating Examples Fig. 1

  15. Advanced heart block in acute rheumatic fever.

    Science.gov (United States)

    Hubail, Zakariya; Ebrahim, Ishaq M

    2016-04-01

    First degree heart block is considered a minor criterion for the diagnosis of this condition. The cases presented here demonstrate that higher degrees of heart block do occur in rheumatic fever. Children presenting with acquired heart block should be worked-up for rheumatic fever. Likewise, it is imperative to serially follow the electrocardiogram in patients already diagnosed with acute rheumatic fever, as the conduction abnormalities can change during the course of the disease.

  16. Advanced heart block in acute rheumatic fever

    OpenAIRE

    2015-01-01

    First degree heart block is considered a minor criterion for the diagnosis of this condition. The cases presented here demonstrate that higher degrees of heart block do occur in rheumatic fever. Children presenting with acquired heart block should be worked-up for rheumatic fever. Likewise, it is imperative to serially follow the electrocardiogram in patients already diagnosed with acute rheumatic fever, as the conduction abnormalities can change during the course of the disease.

  17. Is the high virulence of HIV-1 an unfortunate coincidence of primate lentiviral evolution?

    Science.gov (United States)

    Kirchhoff, Frank

    2009-06-01

    In the subset of primate lentiviruses that contain a vpu gene - HIV-1 and its simian precursors - the Nef protein has lost the ability to down-modulate CD3, block T cell activation and suppress programmed death. Vpu counteracts a host restriction factor induced by the inflammatory cytokine interferon-alpha. I propose that the acquisition of vpu may have allowed the viral lineage that gave rise to HIV-1 to evolve towards greater pathogenicity by removing the selective pressure for a protective Nef function that prevents damagingly high levels of immune activation.

  18. HIV-1 Reverse Transcriptase based assay to determine cellular dNTP concentrations

    Science.gov (United States)

    Hollenbaugh, Joseph A.; Kim, Baek

    2016-01-01

    Summary Deoxynucleoside triphosphates (dNTPs) are the building blocks of DNA and their biosynthesis are tightly regulated in the cell. HPLC-MS and enzyme-based methods are currently employed to determine dNTP concentrations from cellular extracts. Here, we describe a highly efficient, HIV-1 reverse transcriptase (RT)-based assay to quantitate dNTP concentrations. The assay is based on the ability of HIV-1 RT to function at very low dNTP concentrations, thus providing for the high sensitivity of detection. PMID:26714705

  19. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Weijun Zhu

    Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

  20. Punica granatum (Pomegranate juice provides an HIV-1 entry inhibitor and candidate topical microbicide

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2004-10-01

    Full Text Available Abstract Background For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Methods Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1 infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2 binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. Results HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Conclusion These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.