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Sample records for actinohivin blocks hiv

  1. Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120

    X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P212121 symmetry to exhibit an apparent space group P213 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O3 and O4 atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O1 atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features provide strong evidence indicating that AH is

  2. Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120

    Hoque, M. Mominul [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Rajshahi University, Rajshahi (Bangladesh); Suzuki, Kaoru [Iwaki Meisei University, Iwaki, Fukushima 970-8551 (Japan); Tsunoda, Masaru; Jiang, Jiandong; Zhang, Fang; Takahashi, Atsushi; Ohbayashi, Naomi; Zhang, Xiaoxue [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tanaka, Haruo [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); KIIM Pharmaceutical Laboratories Inc., Fukushima 970-8551 (Japan); Ōmura, Satoshi [Kitasato University, Tokyo 108-8641 (Japan); Takénaka, Akio, E-mail: atakenak@sakura.email.ne.jp [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tokyo Institute of Technology, Yokohama 226-8501 (Japan)

    2012-12-01

    X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P2{sub 1}2{sub 1}2{sub 1} symmetry to exhibit an apparent space group P2{sub 1}3 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O{sup 3} and O{sup 4} atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O{sup 1} atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features

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

    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

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

    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.

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

    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

  6. Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervical organ cultures.

    Fraietta, Joseph A; Mueller, Yvonne M; Lozenski, Karissa L; Ratner, Deena; Boesteanu, Alina C; Hancock, Aidan S; Lackman-Smith, Carol; Zentner, Isaac J; Chaiken, Irwin M; Chung, Suhman; LeGrice, Stuart F J; Snyder, Beth A; Mankowski, Marie K; Jones, Natalie M; Hope, Jennifer L; Gupta, Phalguni; Anderson, Sharon H; Wigdahl, Brian; Katsikis, Peter D

    2014-12-01

    In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2' deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

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

    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

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

    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.

  9. A Haplotype Block Model for Fine Mapping of Quantitative Trait Loci Regulating HIV-1 Pathogenesis

    Zhu, Yun; Hou, Wei; Wu, Rongling

    2003-01-01

    The dynamic change of human immunodeficiency virus type-1 (HIV-1) particles that cause AIDS displays considerable variation from patients to patients. It is likely that such variation in HIV-1 pathogenesis is correlated with the genetic architecture of hosts. Traditional genetic analysis of HIV-1 infection is based on various biochemical approaches, but it has been little successful because HIV-1 dynamics, as a complex trait, is under polygenic control and sensitive to environmental changes. ...

  10. Small-Molecule Inhibitors of the LEDGF/p75 Binding Site of Integrase Block HIV Replication and Modulate Integrase Multimerization

    Christ, Frauke; Shaw, Stephen; Demeulemeester, Jonas; Desimmie, Belete A.; Marchand, Arnaud; Butler, Scott; Smets, Wim; Chaltin, Patrick; Westby, Mike

    2012-01-01

    Targeting the HIV integrase (HIV IN) is a clinically validated approach for designing novel anti-HIV therapies. We have previously described the discovery of a novel class of integration inhibitors, 2-(quinolin-3-yl)acetic acid derivatives, blocking HIV replication at a low micromolar concentration through binding in the LEDGF/p75 binding pocket of HIV integrase, hence referred to as LEDGINs. Here we report the detailed characterization of their mode of action. The design of novel and more potent analogues with nanomolar activity enabled full virological evaluation and a profound mechanistic study. As allosteric inhibitors, LEDGINs bind to the LEDGF/p75 binding pocket in integrase, thereby blocking the interaction with LEDGF/p75 and interfering indirectly with the catalytic activity of integrase. Detailed mechanism-of-action studies reveal that the allosteric mode of inhibition is likely caused by an effect on HIV-1 integrase oligomerization. The multimodal inhibition by LEDGINs results in a block in HIV integration and in a replication deficiency of progeny virus. The allosteric nature of LEDGINs leads to synergy in combination with the clinically approved active site HIV IN strand transfer inhibitor (INSTI) raltegravir, and cross-resistance profiling proves the distinct mode of action of LEDGINs and INSTIs. The allosteric nature of inhibition and compatibility with INSTIs underline an interest in further (clinical) development of LEDGINs. PMID:22664975

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

    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.

  12. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Mini Balakrishnan

    Full Text Available HIV-1 integrase (IN is the target for two classes of antiretrovirals: i the integrase strand-transfer inhibitors (INSTIs and ii the non-catalytic site integrase inhibitors (NCINIs. NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly.

  13. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Balakrishnan, Mini; Yant, Stephen R; Tsai, Luong; O'Sullivan, Christopher; Bam, Rujuta A; Tsai, Angela; Niedziela-Majka, Anita; Stray, Kirsten M; Sakowicz, Roman; Cihlar, Tomas

    2013-01-01

    HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA) integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly. PMID:24040198

  14. 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

    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

  15. Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells

    Titanji, Boghuma; Aasa-Chapman, Marlen; Pillay, Deenan; Jolly, Clare

    2013-01-01

    Background; The Human Immunodeficiency Virus type-1 (HIV-1) spreads by cell-free diffusion and by direct cell-to-cell transfer, the latter being a significantly more efficient mode of transmission. Recently it has been suggested that cell-to-cell spread may permit ongoing virus replication in the presence of antiretroviral therapy (ART) based on studies performed using Reverse Transcriptase Inhibitors (RTIs). Protease Inhibitors (PIs) constitute an important component of ART; however whether ...

  16. Novel branched isocyanides as useful building blocks in the Passerini-amine deprotection-acyl migration (PADAM) synthesis of potential HIV-1 protease inhibitors

    Gravestock, David; Lourens, Anna C. U.; Rousseau, Amanda L.; Hoppe, Heinrich C; Nkabinde, Lindiwe A.; Bode, Moira L.

    2012-01-01

    Novel branched isocyanides have been prepared from L-serine and used as building blocks in the Passerini- amine deprotection-acyl migration (PADAM) sequence for the preparation of compounds with activity against HIV-1 protease. http://www.journals.elsevier.com/tetrahedron-letters/ The authors wish to thank the Innovation Fund (now the Technology Innovation Agency, South Africa) for financial support

  17. HIV-protease inhibitors block the replication of both vesicular stomatitis and influenza viruses at an early post-entry replication step

    The inhibitors of HIV-1 protease (PIs) have been designed to block the activity of the viral aspartyl-protease. However, it is now accepted that this family of inhibitors can also affect the activity of cell proteases. Since the replication of many virus species requires the activity of host cell proteases, investigating the effects of PIs on the life cycle of viruses other than HIV would be of interest. Here, the potent inhibition induced by saquinavir and nelfinavir on the replication of both vesicular stomatitis and influenza viruses is described. These are unrelated enveloped RNA viruses infecting target cells upon endocytosis and intracellular fusion. The PI-induced inhibition was apparently a consequence of a block at the level of the fusion between viral envelope and endosomal membranes. These findings would open the way towards the therapeutic use of PIs against enveloped RNA viruses other than HIV.

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

    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.

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

    Ferreira, Victor H; Nazli, Aisha; Dizzell, Sara E; Mueller, Kristen; Kaushic, Charu

    2015-01-01

    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. PMID:25856395

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

    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. Explore the Blocking Method on Maternal-infant Vertical Transmission in Pregnancy with HIV Infection%妊娠合并 HIV 感染母婴垂直传播阻断措施探讨

    赵娟; 朱红梅; 李平; 袁子清; 蒋惠如

    2014-01-01

    Objective:Toexplorethematernal-infantverticaltransmissionblockingmethodonthepregnancywithHIVinfection.Methods:sixteenHIV-infectionpregnantcasesweregiventothematernal-infantblockingmethod, such as anti-viral medicine therapy, cesareansection, artificialfeedingandsoon.Results:Exceptfortwocaseswerelost to follow up,therestfourteencasesofinfantweretestedHIV-antibodynegativetwice.Conclusion:Forexpectantmothers with HIV, it is essential adopt maternal-infant blocking methods including perinatal care,prenatalantiviraldrugs,obstetric intervention and artificial feeding of newborns are important measures to decrease the number of the AIDS children.%目的:探讨阻断 HIV/AIDS 母婴垂直传播的具体措施。方法:回顾性分析16例妊娠合并 HIV 感染者采取抗病毒药物、分娩期产科干预、人工喂养等综合措施治疗效果。结果:16例孕妇分娩的16例新生儿,失访2例,余14例新生儿两次 HIV 检测均为阴性。结论:对 HIV 感染的孕妇,应做好围生期管理,抗反转录病毒药物阻断,分娩期产科干预,新生儿人工喂养的母婴阻断综合措施是降低 HIV 感染母婴传播的有效措施。

  2. 妊娠合并 HIV 感染母婴垂直传播阻断措施探讨%Explore the Blocking Method on Maternal-infant Vertical Transmission in Pregnancy with HIV Infection

    赵娟; 朱红梅; 李平; 袁子清; 蒋惠如

    2014-01-01

    目的:探讨阻断 HIV/AIDS 母婴垂直传播的具体措施。方法:回顾性分析16例妊娠合并 HIV 感染者采取抗病毒药物、分娩期产科干预、人工喂养等综合措施治疗效果。结果:16例孕妇分娩的16例新生儿,失访2例,余14例新生儿两次 HIV 检测均为阴性。结论:对 HIV 感染的孕妇,应做好围生期管理,抗反转录病毒药物阻断,分娩期产科干预,新生儿人工喂养的母婴阻断综合措施是降低 HIV 感染母婴传播的有效措施。%Objective:Toexplorethematernal-infantverticaltransmissionblockingmethodonthepregnancywithHIVinfection.Methods:sixteenHIV-infectionpregnantcasesweregiventothematernal-infantblockingmethod, such as anti-viral medicine therapy, cesareansection, artificialfeedingandsoon.Results:Exceptfortwocaseswerelost to follow up,therestfourteencasesofinfantweretestedHIV-antibodynegativetwice.Conclusion:Forexpectantmothers with HIV, it is essential adopt maternal-infant blocking methods including perinatal care,prenatalantiviraldrugs,obstetric intervention and artificial feeding of newborns are important measures to decrease the number of the AIDS children.

  3. CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

    Le Borgne, Sylvie; Février, Michèle; Callebaut, Christian; Lee, Steven P.; Rivière, Yves

    2000-01-01

    CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector pha...

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

    Farr, Christina; Nomellini, John F; Ailon, Evan; Shanina, Iryna; Sangsari, Sassan; Cavacini, Lisa A; Smit, John; Horwitz, Marc S

    2013-01-01

    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. PMID:23840383

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

    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.

  6. Computer-aided design of novel HIV-1 entry inhibitors blocking the virus envelope gp120 V3 loop

    Tuzikov A. V.

    2012-12-01

    Full Text Available Aim. The object of this study was to implement computer-aided design of the water-soluble analog of glycolipid β -galactosylceramide (β-GalCer, which presents a potential HIV-1 entry inhibitor, by the analysis of intermolecular interactions of β-GalCer with the central region of the virus envelope gp120 V3 loop followed by synthesis of this glycolipid derivative and testing for antiviral activity. Methods. To reach the object of view, computer modeling procedures, such as quantum chemical calculations, molecular docking, molecular dynamics and free energy simulations, were involved in the studies in conjunction with chemical synthesis and anti-HIV-1 assay methods. Results. As a result, the high probability of exhibiting of antiviral activity was predicted for the designed β-GalCer analog. The data of molecular modeling were confirmed by those of primary medical trials of the synthesized compound. Conclusions. In the light of the findings obtained, the designed analog of β-GalCer may be considered as the basic structure for simulation of its more potent structural forms and for posterior selection of drug candidates most promising for synthesis and anti-HIV-1 assays.

  7. Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells

    Fenard, David; Lambeau, Gérard; Valentin, Emmanuel; Lefebvre, Jean-Claude; Lazdunski, Michel; Doglio, Alain

    1999-01-01

    Mammalian and venom secreted phospholipases A2 (sPLA2s) have been associated with a variety of biological effects. Here we show that several sPLA2s protect human primary blood leukocytes from the replication of various macrophage and T cell–tropic HIV-1 strains. Inhibition by sPLA2s results neither from a virucidal effect nor from a cytotoxic effect on host cells, but it involves a more specific mechanism. sPLA2s have no effect on virus binding to cells nor on syncytia formation, but they pre...

  8. The Anti-Inflammatory Activity of Curcumin Protects the Genital Mucosal Epithelial Barrier from Disruption and Blocks Replication of HIV-1 and HSV-2

    Ferreira, Victor H; Nazli, Aisha; Dizzell, Sara E.; Mueller, Kristen; Kaushic, Charu

    2015-01-01

    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 ...

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

    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. PMID:17168681

  10. Study on blocking measures of mother-to-child in HIV positive pregnant women%HIV阳性孕产妇母婴阻断措施的临床效果

    郑美玲; 胡玉玲

    2013-01-01

    目的:探讨对HIV阳性孕产妇的新生儿予以HIV的阻断措施的临床效果.方法:设定阻断技术路线,对HIV阳性孕产妇根据孕期实施不同的阻断措施,并对采取完全阻断、不完全阻断及未采取阻断措施的新生儿HIV的阴性率进行比较分析.结果:2005年至2010年各年度有关HIV母婴阻断传播的咨询率逐年上升,HIV阳性检出率为0.3%~0.6%;共114名HIV阳性孕产妇,87例(76.3%)选择继续妊娠者中85例围生儿存活.87例中51例采用了完全阻断措施,其新生儿HIV阴性率为98.0%;29例予以不完全阻断措施,其新生儿HIV阴性率为72.4%;未采取阻断7例(1例失访),新生儿HIV阴性率为0.结论:根据孕期时间实施完全阻断措施可有效降低HIV母婴传播率,提高新生儿生存质量,对遏制婴儿和儿童人群艾滋病的传播有重要意义.%Objective; To discuss blocking effect on different blocking measures of maternal to child in HIV positive maternal neonatal. Methods; Blocking technology route was set up and different blocking measures was implemented on HIV-positive pregnant women according to the pregnancy time. HIV-negative rate of newborn who complete block, incomplete block or no preventive measures were carried out was compared and analyzed. Results: Annual consulting rate increased year by year from 2005 to 2010, HIV-positive detection rate was 0. 3%-0. 6 %. There were 114 cases of positive pregnant women, in which 87 cases(76. 3% ) chose to continue pregnancy and 85 cases of perinatal child survival. Fifty- one cases of neonatal were given complete block measures and their HIV-negative rate was 98. 0%. Twenty-nine cases of neonatal were given incomplete block measures and their HIV-negative rate was 72.4% . Seven cases of neonatal were not given preventive measures and whose negative rate was 0. Conclusion: According to the pregnancy time, implement of complete block measures can effectively reduce HIV mother- to- child

  11. 36例妊娠合并HIV感染孕产妇母婴阻断措施的探讨%Explore the Mother-to-child Blocking Method on 36 Cases of the Pregnancy with HIV Infection

    魏红; 周敏; 曾丽; 金燕; 陈竹

    2012-01-01

      Objective To explore the mother-to-child blocking method on the pregnancy with HIV infection. Methods Thirty-six HIV-infection pregnant cases were given the mother-to-child blocking method, such as anti-viral medicine therapy, Cesarean section, artificial feeding and so on. Results Except for one case lost to follow up, two cases HIV-antibody positive, the lastr thirty-three cases of infant (91.7%) were HIV-antibody negative twice. Conclusion The mother-to-child blocking methods including prenatal Antiviral drugs,Obstetric intervention and artificial feeding of newborns were important measures to decrease the number of the AIDS children.%  目的探讨妊娠合并HIV感染孕产妇的母婴阻断的措施.方法本院2009年1月至2011年2月收治的36例HIV感染孕妇采取抗病毒药物、选择性剖宫产、人工喂养等综合措施.结果除1例失访,2例新生儿HIV抗体阳性,余33例(91.7%)新生儿两次HIV抗体均为阴性.结论产前抗病毒药物阻断、分娩期产科干预联合新生儿人工喂养的母婴阻断措施是有效降低母婴传播率、控制儿童艾滋病传播病的重要措施.

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

    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

    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

    Tomaras, Georgia D.; Ferrari, Guido; Shen, Xiaoying; Alam, S. Munir; Liao, Hua-Xin; Pollara, Justin; Bonsignori, Mattia; Moody, M. Anthony; Fong, Youyi; Chen, Xi; Poling, Brigid; Nicholson, Cindo O.; Zhang, Ruijun; Lu, Xiaozhi; Parks, Robert,

    2013-01-01

    Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses directly correlated with risk. In the secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate of risk, but only in the presence of low plasma IgA Env-specific antibodies. Thus, we investigated the hypoth...

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

    Li Yun-Yao; Strick Nathan; Neurath A Robert; Debnath Asim K

    2001-01-01

    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. Met...

  16. Azasugar-Containing Phosphorothioate Oligonucleotide (AZPSON) DBM-2198 Inhibits Human Immunodeficiency Virus Type 1 (HIV-1) Replication by Blocking HIV-1 gp120 without Affecting the V3 Region

    Lee, Jinjoo; Byeon, Se Eun; Jung, Ju Yeol; Kang, Myeong-Ho; Park, Yu-Jin; Jung, Kyeong-Eun; Bae, Yong-Soo

    2015-01-01

    DBM-2198, a six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON), was described in our previous publication [Lee et al. (2005)] with regard to its antiviral activity against a broad spectrum of HIV-1 variants. This report describes the mechanisms underlying the anti-HIV-1 properties of DBM-2198. The LTR-mediated reporter assay indicated that the anti-HIV-1 activity of DBM-2198 is attributed to an extracellular mode of action rather than intrace...

  17. HIV Transmission

    ... 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 Español (Spanish) Recommend on Facebook ...

  18. Drugs That Fight HIV-1

    ... program of the National Institutes of Health Nucleoside Reverse Transcriptase Inhibitors (NRTIs) NRTIs block reverse transcriptase, an enzyme HIV- ... these products are on last page.) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) NNRTIs bind to and alter reverse transcriptase, ...

  19. FDA-Approved HIV Medicines

    ... and acronyms) Brand Name FDA Approval Date Nucleoside Reverse Transcriptase Inhibitors (NRTIs) NRTIs block reverse transcriptase, an enzyme HIV ... AZT, ZDV) Retrovir March 19, 1987 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) NNRTIs bind to and later alter reverse ...

  20. Heart Block

    ... the signal causes the heart to contract and pump blood. Heart block occurs if the electrical signal is ... degree heart block limits the heart's ability to pump blood to the rest of the body. This type ...

  1. Population Blocks.

    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…

  2. HIV Symptoms

    ... Submit Home > HIV/AIDS > What is HIV/AIDS? HIV/AIDS This information in Spanish ( en español ) HIV symptoms Photo courtesy of AIDS.gov More information ... and brain Return to top More information on HIV symptoms Explore other publications and websites Basic Information ...

  3. HIV Testing

    ... 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 ...

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

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

    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....

  5. Ghost Block

    Webb, Neil

    2011-01-01

    Filmed on the English south coast 'Ghost Block' depicts the uncanny and eerie atmosphere at the site of a WW2 coastal defence line. The concrete cubes were used as an anti-invasion blockade against potential landing forces. This protection line now slowly decaying and becoming enmeshed into the environment still acts as a defence to repel unwanted visitors. The area is a natural reserve to nesting birds that often lay eggs directly onto the beach surface. The blocks act as a final barrier ...

  6. Women and HIV

    ... 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 ...

  7. 2010-2013年梧州市艾滋病母婴传播阻断综合模式实施成效分析%Analysis on the effectiveness of HIV maternal-neonatal transmission block comprehensive mode in Wuzhou city from 2010 to 2013

    陈秋玲; 李论; 罗莹; 庞义坚; 周宇珍; 卢郁全; 王盛侃

    2016-01-01

    Objective To understand the effectiveness of HIV maternal-neonatal transmission block comprehensive mode in Wuzhou city by analyzing the monitoring data of HIV maternal-neonatal transmission block work in Wuzhou city from 2010 to 2013.Methods From 2010 to 2013,the monitoring data of HIV maternal-neonatal transmission prevention consultation rates and HIV antibody detection rates of premarital health care population and pregnant women,antiviral drug application rates of HIV-infected pregnant women,antiviral drug application rates of babies born by HIV-infected pregnant women,HIV detection rate and HIV definitely diagnostic rate of infants at 18 months born by HIV-infected pregnant women,the artificial termination rate of pregnancy of pregnant women with positive HIV in Wuzhou city was collected,then the data was analyzed by Excel 2003 and SPSS 16.0 software.Results From 2010 to 2013,HIV maternal-neonatal transmission prevention consultation rates of premarital health care population were 99.73%,100.00%,100.00%,and 100.00%,respectively,there was statistically significant difference among different years (x2 =440.526 8,P<0.05);HIV antibody detection rates of premarital health care population were 98.64%,99.86%,100.00%,and 100.00%,respectively,there was statistically significant difference among different years (x2=1 852.401 2,P<0.05);HIV maternal-neonatal transmission prevention consultation rates of pregnant women were 93.70%,99.71%,99.96%,and 99.98%,respectively,there was statistically significant difference among different years (x2 =10 399.748 5,P<0.05);HIV antibody detection rates of pregnant women were 96.52%,99.59%,99.96%,and 99.98%,respectively,there was statistically significant difference among different years (x2 =508 6.239 3,P<0.05);antiviral drug application rates of HIV-infected pregnant women were 65.38%,80.77%,94.12%,and 90.28%,respectively,there was statistically significant difference among different

  8. 2010-2013年梧州市艾滋病母婴传播阻断综合模式实施成效分析%Analysis on the effectiveness of HIV maternal-neonatal transmission block comprehensive mode in Wuzhou city from 2010 to 2013

    陈秋玲; 李论; 罗莹; 庞义坚; 周宇珍; 卢郁全; 王盛侃

    2016-01-01

    =11.818 7,P<0.05).结论 通过实施梧州市HIV母婴阻断全方位多层次多平台合作模式,婚前保健人群预防HIV母婴传播咨询率和抗体检测率、孕产妇预防HIV母婴传播咨询率和抗体检测率、感染HIV孕产妇抗病毒药物应用率、感染孕产妇所分娩婴儿药物应用率、HIV阳性孕产妇人工终止妊娠率均显著升高,在提高人群预防HIV母婴传播的意识、预防青年及育龄妇女感染HIV、减少HIV母婴传播和减少HIV感染婴儿的出生等方面取得了积极成效.%Objective To understand the effectiveness of HIV maternal-neonatal transmission block comprehensive mode in Wuzhou city by analyzing the monitoring data of HIV maternal-neonatal transmission block work in Wuzhou city from 2010 to 2013.Methods From 2010 to 2013,the monitoring data of HIV maternal-neonatal transmission prevention consultation rates and HIV antibody detection rates of premarital health care population and pregnant women,antiviral drug application rates of HIV-infected pregnant women,antiviral drug application rates of babies born by HIV-infected pregnant women,HIV detection rate and HIV definitely diagnostic rate of infants at 18 months born by HIV-infected pregnant women,the artificial termination rate of pregnancy of pregnant women with positive HIV in Wuzhou city was collected,then the data was analyzed by Excel 2003 and SPSS 16.0 software.Results From 2010 to 2013,HIV maternal-neonatal transmission prevention consultation rates of premarital health care population were 99.73%,100.00%,100.00%,and 100.00%,respectively,there was statistically significant difference among different years (x2 =440.526 8,P<0.05);HIV antibody detection rates of premarital health care population were 98.64%,99.86%,100.00%,and 100.00%,respectively,there was statistically significant difference among different years (x2=1 852.401 2,P<0.05);HIV maternal-neonatal transmission prevention consultation rates of pregnant women

  9. Epidural block

    ... Drugs & Supplements Videos & Tools Español You Are Here: Home ... It numbs or causes a loss of feeling in the lower half your body. This lessens the pain of contractions during childbirth. An epidural block may also be used to ...

  10. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Arun K. Nalla; Trobridge, Grant D.

    2016-01-01

    Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a pote...

  11. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  12. HIV Prevention

    ... PrEP PEP Living With HIV Opportunistic Infections Travel Abroad Treatment Basic Statistics Get Tested Find an HIV ... kill or neutralize viruses and bacteria. Researchers are studying both vaginal and rectal microbicides to see if ...

  13. Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment

    Lu Wuyuan

    2011-06-01

    Full Text Available Abstract Background Concurrent sexually transmitted infections (STIs increase the likelihood of HIV transmission. The levels of defensins are frequently elevated in genital fluids from individuals with STIs. We have previously shown that human defensins 5 and 6 (HD5 and HD6 promote HIV entry and contribute to Neisseria gonorrhoeae-mediated enhancement of HIV infectivity in vitro. In this study, we dissect the molecular mechanism of the HIV enhancing effect of defensins. Results HD5 and HD6 primarily acted on the virion to promote HIV infection. Both HD5 and HD6 antagonized the anti-HIV activities of inhibitors of HIV entry (TAK 779 and fusion (T-20 when the inhibitors were present only during viral attachment; however, when these inhibitors were added back during viral infection they overrode the HIV enhancing effect of defensins. HD5 and HD6 enhanced HIV infectivity by promoting HIV attachment to target cells. Studies using fluorescent HIV containing Vpr-GFP indicated that these defensins enhanced HIV attachment by concentrating virus particles on the target cells. HD5 and HD6 blocked anti-HIV activities of soluble glycosaminoglycans including heparin, chondroitin sulfate, and dextran sulfate. However, heparin, at a high concentration, diminished the HIV enhancing effect of HD5, but not HD6. Additionally, the degree of the HIV enhancing effect of HD5, but not HD6, was increased in heparinase-treated cells. These results suggest that HD5 and haparin/heparan sulfate compete for binding to HIV. Conclusions HD5 and HD6 increased HIV infectivity by concentrating virus on the target cells. These defensins may have a negative effect on the efficacy of microbicides, especially in the setting of STIs.

  14. Blocked strainers

    Thermal insulation was the cause of the blockages that shut down five BWRs in Sweden. The main culprit was mineral wool installed when the plants started up. Physical degradation of the wool over the lifetime of the plant meant it could easily be washed out of place during a loss of coolant accident and could quickly block strainers in the emergency core cooling systems. The five BWRs are almost all back on line, equipped with larger strainers and faster backwashing capability. But the incident prompted more detailed investigation into how materials in the containment would behave during an accident. One material that caused particular concern is Caposil, a material often used to insulate the reactor vessel. Composed of natural calcium, aluminium silicates and cellulose fibres, in the event of a LOCA Caposil becomes particularly hazardous. Under high pressure, or when brought into contact with high pressure water and steam, Caposil fragments into 1 cm clumps, free fibres, and ''fines''. It is these fines which cause major problems and can block a strainer extremely quickly. The successful testing of a high performance water filter which can handle Caposil is described. (4 figures) (Author)

  15. HIV Treatment: The Basics

    HIV Treatment HIV Treatment: The Basics (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  16. HIV Prevention

    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.

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

    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. PMID:27092564

  18. Get Tested for HIV

    ... Submit Home > HIV/AIDS > Get tested for HIV HIV/AIDS This information in Spanish ( en español ) Get tested for HIV When should I get tested for HIV? Types ... to top More information on Get tested for HIV Explore other publications and websites HIV Anonymous Testing, ...

  19. TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core.

    Valle-Casuso, Jose Carlos; Di Nunzio, Francesca; Yang, Yang; Reszka, Natalia; Lienlaf, Maritza; Arhel, Nathalie; Perez, Patricio; Brass, Abraham L.; Diaz-Griffero, Felipe

    2012-01-01

    International audience TNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to integration. To investigate the mechanistic requirement of TNPO3 in HIV-1 infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3 binds to the HIV-1 core. Overall, this work suggests that TNPO3 interacts with the incoming HIV-1 core in the cytoplasm to assist a process that is important for ...

  20. Molecular dynamics simulations of HIV-1 protease complexed with saquinavir

    Watson, S. J.

    2009-01-01

    Inhibition of the Human Immunode�ficiency virus type-1 (HIV-1) protease enzyme blocks HIV-1 replication. Protease inhibitor drugs have successfully been used as a therapy for HIV-infected individuals to reduce their viral loads and slow the progression to Acquired Immune Defi�ciency Syndrome (AIDS). However, mutations readily and rapidly accrue in the protease gene resulting in a reduced sensitivity of the protein to the inhibitor. In this thesis, molecular dynamics simulations (MDS)...

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

    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.

  2. Removal of Vaccinia Virus Genes That Block Interferon Type I and II Pathways Improves Adaptive and Memory Responses of the HIV/AIDS Vaccine Candidate NYVAC-C in Mice

    Gómez, Carmen Elena; Perdiguero, Beatriz; Nájera, Jose Luis; Sorzano, Carlos Oscar S.; Jiménez, Victoria; González-Sanz, Rubén; Esteban, Mariano

    2012-01-01

    Poxviruses encode multiple inhibitors of the interferon (IFN) system, acting at different levels and blocking the induction of host defense mechanisms. Two viral gene products, B19 and B8, have been shown to act as decoy receptors of type I and type II IFNs, blocking the binding of IFN to its receptor. Since IFN plays a major role in innate immune responses, in this investigation we asked to what extent the viral inhibitors of the IFN system impact the capacity of poxvirus vectors to activate...

  3. HIV/AIDS

    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 ...

  4. HIV and Pregnancy

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

  5. HIV Medication Adherence

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  6. HIV and Rheumatic Disease

    ... 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 ...

  7. HIV and AIDS

    ... Got Homework? Here's Help White House Lunch Recipes 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 ...

  8. HIV Antibody Test

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  9. 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.

    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.

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

    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

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

    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.

  12. Ultrasound guided supraclavicular block.

    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.

  13. Drugs + HIV, Learn the Link

    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 ). ...

  14. Screening and diagnosis for HIV

    HIV testing; HIV screening; HIV screening test; HIV confirmatory test ... A positive result on a screening test does not confirm that the person has HIV infection. More tests are needed to confirm HIV infection. A negative test ...

  15. HIV among Women

    ... 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 Language: English Español (Spanish) Format: Select ...

  16. Tannin inhibits HIV-1 entry by targeting gp41

    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.

  17. Mechanisms of inhibition of HIV replication by nonnucleoside reverse transcriptase inhibitors

    Sluis-Cremer, Nicolas; Tachedjian, Gilda

    2008-01-01

    The nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are a therapeutic class of compounds that are routinely used, in combination with other antiretroviral drugs, to treat HIV-1 infection. NNRTIs primarily block HIV-1 replication by preventing RT from completing reverse transcription of the viral single-stranded RNA genome into DNA. However, some NNRTIs, such as efavirenz, have been shown to inhibit the late stages of HIV-1 replication by interfering with HIV-1 Gag-Pol polyprotein...

  18. Chemokines, lymphocytes, and HIV

    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

  19. Block clustering with collapsed latent block models

    Wyse, Jason; Friel, Nial

    2010-01-01

    We introduce a Bayesian extension of the latent block model for model-based block clustering of data matrices. Our approach considers a block model where block parameters may be integrated out. The result is a posterior defined over the number of clusters in rows and columns and cluster memberships. The number of row and column clusters need not be known in advance as these are sampled along with cluster memberhips using Markov chain Monte Carlo. This differs from existing work on latent bloc...

  20. A novel peptide that inhibits HIV-1 entry

    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].

  1. MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1

    Fricke, Thomas; White, Tommy E; Schulte, Bianca; de Souza Aranha Vieira, Daniel A.; Dharan, Adarsh; Campbell, Edward M; Brandariz-Nuñez, Alberto; Diaz-Griffero, Felipe

    2014-01-01

    Background The IFN-α-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Genetic evidence suggested that capsid is the viral determinant for restriction by MxB. This work explores the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in restriction. Results We showed that MxB binds to the HIV-1 core and that this interaction leads to inhibition of the uncoating process of HIV-1. These results identify MxB as an e...

  2. The anti-HIV activity of ADS-J1 targets the HIV-1 gp120

    Recent data suggest that heparin sulfates may bind to a CD4 induced epitope in the HIV-1 gp120 that constitutes the coreceptor binding site. We have studied the mechanism of action of ADS-J1, a non-peptidic compound selected by docking analysis to interact with gp41 and to interfere with the formation of N-36/C-34 complexes in sandwich ELISA experiments. We show that ADS-J1 blocked the binding of wild-type HIV-1 NL4-3 strain to MT-4 cells but not virus-cell binding of a polyanion-resistant virus. However, ADS-J1 blocked the replication of polyanion-resistant, T-20- and C34-resistant HIV-1, suggesting a second mechanism of action. Development of resistance to ADS-J1 on the polyanion-resistant HIV-1 led to mutations in gp120 coreceptor binding site and not in gp41. Time of addition experiments confirmed that ADS-J1, but not polyanions such as dextran sulfate or AR177, worked at a step that mimics the activity of an HIV coreceptor antagonist but prior to gp41-dependent fusion. We conclude that ADS-J1 may bind to the HIV coreceptor binding site as its mechanism of anti-HIV activity

  3. Incomplete block designs

    Dey, Aloke

    2010-01-01

    This book presents a systematic, rigorous and comprehensive account of the theory and applications of incomplete block designs. All major aspects of incomplete block designs are considered by consolidating vast amounts of material from the literature - the classical incomplete block designs, like the balanced incomplete block (BIB) and partially balanced incomplete block (PBIB) designs. Other developments like efficiency-balanced designs, nested designs, robust designs, C-designs and alpha designs are also discussed, along with more recent developments in incomplete block designs for special t

  4. HIV Life Cycle

    HIV Overview The HIV Life Cycle (Last updated 9/22/2015; last reviewed 9/22/2015) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

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

    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.

  6. Drugs + HIV, Learn the Link

    Full Text Available ... help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) ... National Center for HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/ ...

  7. Drugs + HIV, Learn the Link

    Full Text Available ... HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/ ... STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). Atlanta, ...

  8. Basic HIV/AIDS Statistics

    ... HIV Syndicated Content Website Feedback HIV/AIDS Basic Statistics Language: English Español (Spanish) Recommend on Facebook Tweet ... HIV. Interested in learning more about CDC's HIV statistics? Terms, Definitions, and Calculations Used in CDC HIV ...

  9. Postural heart block.

    Seda, P E; McAnulty, J H; Anderson, C J

    1980-01-01

    A patient presented with orthostatic dizziness and syncope caused by postural heart block. When the patient was supine, atrioventricular conduction was normal and he was asymptomatic; when he was standing he developed second degree type II block and symptoms. The left bundle-branch block on his electrocardiogram and intracardiac electrophysiological study findings suggest that this heart block occurred distal to the His bundle. Orthostatic symptoms are usually presumed to be secondary to an i...

  10. μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

    A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3+ lymphoblasts and CD14+ monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

  11. Women and HIV

    ... on HIV testing. Gynecological problems can be early signs of HIV infection . Ulcers in the vagina, persistent yeast infections, and severe pelvic inflammatory disease (PID) can be signs of HIV. Hormone changes, birth control pills, or antibiotics can ...

  12. How HIV Causes AIDS

    ... Share this: Main Content Area How HIV Causes AIDS HIV destroys CD4 positive (CD4+) T cells, which ... and disease, ultimately resulting in the development of AIDS. Most people who are infected with HIV can ...

  13. HIV and Immunizations

    HIV Treatment HIV and Immunizations (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Vaccines are products that ... a disease outbreak. Is there a vaccine against HIV? Testing is underway on experimental vaccines to prevent ...

  14. HIV-AIDS Connection

    ... Content Marketing Share this: Main Content Area The HIV-AIDS Connection AIDS was first recognized in 1981 ... cancers. Why is there overwhelming scientific consensus that HIV causes AIDS? Before HIV infection became widespread in ...

  15. Preventing HIV with Medicine

    ... HIV/AIDS This information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you ... during sex. Return to top More information on Preventing HIV with medicine Explore other publications and websites ...

  16. HIV/AIDS

    HIV stands for human immunodeficiency virus. It kills or damages the body's immune system cells. AIDS stands ... is the most advanced stage of infection with HIV. HIV most often spreads through unprotected sex with ...

  17. Psychotropic prescribing in HIV

    Reid, E; Orrell, C.; K Stoloff; Joska, J.

    2012-01-01

    Psychiatric disorders frequently co-occur with HIV, as preceding conditions or consequent to HIV infection. This potentially compromises HIV diagnosis and antiretroviral (ARV) treatment adherence. We provide a brief guide to the diagnosis and treatment of common mental disorders in people living with HIV/AIDS, including: prescribing psychotropics in HIV; neuropsychiatric side-effects of ARVs and other medications commonly prescribed in HIV; and the diagnosis and treatment of depression, anxie...

  18. Generalized Block Failure

    Jönsson, Jeppe

    2015-01-01

    shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along......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....

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

    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.

  20. Thirty years on: HIV receptor gymnastics and the prevention of infection.

    Weiss, Robin A

    2013-01-01

    During 30 years of research on human immunodeficiency virus (HIV), our knowledge of its cellular receptors--CD4, CCR5 and CXCR4--has illuminated aspects of the pathogenesis of the acquired immune deficiency syndrome (AIDS). Studying how the HIV envelope glycoproteins interact with the receptors led to anti-retroviral drugs based on blocking the docking or fusion of virus to the host cell. Genetic polymorphisms of CCR5 determine resistance to HIV infection and the rate of progression to AIDS. Eliciting neutralizing antibodies to the sites of receptor interaction on HIV glycoproteins is a promising approach to HIV vaccine development. PMID:23692808

  1. Contribution of MxB Oligomerization to HIV-1 Capsid Binding and Restriction

    Buffone, Cindy; Schulte, Bianca; OPP, Silvana; Diaz-Griffero, Felipe

    2015-01-01

    The alpha interferon (IFN-α)-inducible restriction factor myxovirus B (MxB) blocks HIV-1 infection after reverse transcription but prior to integration. MxB binds to the HIV-1 core, which is composed of capsid protein, and this interaction leads to inhibition of the uncoating process of HIV-1. Previous studies suggested that HIV-1 restriction by MxB requires binding to capsid. This work tests the hypothesis that MxB oligomerization is important for the ability of MxB to bind to the HIV-1 core...

  2. Blocked Randomization with Randomly Selected Block Sizes

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  3. Blocked randomization with randomly selected block sizes.

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes. PMID:21318011

  4. BLOCK H-MATRICES AND SPECTRUM OF BLOCK MATRICES

    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.

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

    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.

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

    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. PMID:27199430

  7. Lesson Thirteen Trifascicular Block

    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.

  8. Block Advertisement Protocol

    Nemirovsky, Danil

    2015-01-01

    Bitcoin, a decentralized cryptocurrency, has attracted a lot of attention from academia, financial service industry and enthusiasts. The trade-off between transaction confirmation throughput and centralization of hash power do not allow Bitcoin to perform at the same level as modern payment systems. Block Advertisement Protocol is proposed as a step to resolve this issue. The protocol allows block mining and block relaying to happen in parallel. The protocol dictates a miner to advertise the ...

  9. The hunt for HIV-1 integrase inhibitors.

    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. PMID:16839248

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

    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.

  11. National HIV Testing Day

    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.

  12. Eliminating Perinatal HIV Transmission

    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.

  13. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  14. Doctors Report Groundbreaking HIV-To-HIV Organ Transplants

    ... html Doctors Report Groundbreaking HIV-to-HIV Organ Transplants One donor supplied a kidney to one patient ... 30, 2016 (HealthDay News) -- Trailblazing liver and kidney transplants from an HIV-positive donor to HIV-positive ...

  15. Contribution of PDZD8 to Stabilization of the Human Immunodeficiency Virus (HIV-1) Capsid

    Guth, Charles Alexander

    2013-01-01

    Following human immunodeficiency virus (HIV-1) entry into the host cell, the viral capsid gradually disassembles in a process called uncoating. A proper rate of uncoating is important for reverse transcription of the HIV-1 genome. Host restriction factors such as TRIM5alpha; and TRIMCyp bind retroviral capsids and cause premature disassembly, leading to blocks in reverse transcription. Other host factors, such as cyclophilin A, stabilize the HIV-1 capsid and are required for efficient infe...

  16. LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions

    Desimmie, Belete Ayele; Schrijvers, Rik; Demeulemeester, Jonas; Borrenberghs, Doortje; Weydert, Caroline; Thys, Wannes; Vets, Sofie; Van Remoortel, Barbara; Hofkens, Johan; De Rijck, Jan; Hendrix, Jelle; Bannert, Norbert; Gijsbers, Rik; Christ, Frauke; Debyser, Zeger

    2013-01-01

    Background: LEDGINs are novel allosteric HIV integrase (IN) inhibitors that target the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN. They block HIV-1 integration by abrogating the interaction between LEDGF/p75 and IN as well as by allosterically inhibiting the catalytic activity of IN. Results: Here we demonstrate that LEDGINs reduce the replication capacity of HIV particles produced in their presence. We systematically studied the molecular basis of this late...

  17. Block Scheduling Revisited.

    Queen, J. Allen

    2000-01-01

    Successful block scheduling depends on provision of initial and ongoing instructional training. Teaching strategies should vary and include cooperative learning, the case method, the socratic seminar, synectics, concept attainment, the inquiry method, and simulations. Recommendations for maximizing block scheduling are outlined. (Contains 52…

  18. Why AIDS? The Mystery of How HIV Attacks the Immune System.

    Christensen, Damaris

    1999-01-01

    Reviews differing theories surrounding the mystery of how human immunodeficiency virus (HIV) attacks the immune system. Claims that understanding how HIV triggers immune-cell depletion may enable researchers to block its effects. New knowledge could reveal strategies for acquired immune deficiency syndrome (AIDS) therapies that go beyond the drugs…

  19. HIV / AIDS: An Unequal Burden

    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- ...

  20. Drugs + HIV, Learn the Link

    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 ...

  1. Drugs + HIV, Learn the Link

    Full Text Available ... transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug abuse ... access to the latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention clinical trials, ...

  2. RING Domain Mutations Uncouple TRIM5α Restriction of HIV-1 from Inhibition of Reverse Transcription and Acceleration of Uncoating

    Roa, Amanda; Hayashi, Fumiaki; Yang, Yang; Lienlaf, Maritza; Zhou, Jing; Shi, Jiong; Watanabe, Satoru; Kigawa, Takanori; Yokoyama, Shigeyuki; Aiken, Christopher; Diaz-Griffero, Felipe

    2012-01-01

    Rhesus TRIM5α (TRIM5αrh) is a cytosolic protein that potently restricts HIV-1 at an early postentry stage, prior to reverse transcription. The ability of TRIM5αrh to block HIV-1 infection has been correlated with a decrease of pelletable HIV-1 capsid during infection. To genetically dissect the ability of TRIM5α to block reverse transcription, we studied a set of TRIM5αrh RING domain mutants that potently restrict HIV-1 but allow the occurrence of reverse transcription. These TRIM5αrh RING va...

  3. Predictability of blocking

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  4. Block Cipher Analysis

    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......(AES).Wedescribe the mostgeneraltypes ofblock cipher cryptanalysis but concentrate on the algebraic attacks. While the algebraic techniques have been successful oncertainstreamcipherstheirapplicationtoblock ciphershasnot shown any significant results so far. This thesis contributes to the field of algebraic attacks on...... 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....

  5. Psychotropic prescribing in HIV

    E Reid

    2012-11-01

    Full Text Available Psychiatric disorders frequently co-occur with HIV, as preceding conditions or consequent to HIV infection. This potentially compromises HIV diagnosis and antiretroviral (ARV treatment adherence. We provide a brief guide to the diagnosis and treatment of common mental disorders in people living with HIV/AIDS, including: prescribing psychotropics in HIV; neuropsychiatric side-effects of ARVs and other medications commonly prescribed in HIV; and the diagnosis and treatment of depression, anxiety, psychosis, agitation, sleep disturbance, pain, and mania. Psychotropic treatments recommended were drawn primarily from those available in the public sector of South Africa.

  6. Therapeutic HIV Peptide Vaccine

    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...

  7. Genotypic analysis of HIV-1 coreceptor usage

    Thielen, Alexander

    2011-01-01

    The acquired immunodeficiency syndrome (AIDS) is one of the biggest medical challenges in the world today. Its causative pathogen, the human immunodeficiency virus (HIV), is responsible for millions of deaths per year. Although about two dozen antiviral drugs are currently available, progression of the disease can only be delayed but patients cannot be cured. In recent years, the new class of coreceptor antagonists has been added to the arsenal of antiretroviral drugs. These drugs block viral...

  8. Compensatory Substitutions in the HIV-1 Capsid Reduce the Fitness Cost Associated with Resistance to a Capsid-Targeting Small-Molecule Inhibitor

    Shi, Jiong; Zhou, Jing; Halambage, Upul D.; Shah, Vaibhav B.; Burse, Mallori J.; Wu, Hua; Blair, Wade S.; Butler, Scott L.; Aiken, Christopher

    2014-01-01

    The HIV-1 capsid plays multiple roles in infection and is an emerging therapeutic target. The small-molecule HIV-1 inhibitor PF-3450074 (PF74) blocks HIV-1 at an early postentry stage by binding the viral capsid and interfering with its function. Selection for resistance resulted in accumulation of five amino acid changes in the viral CA protein, which collectively reduced binding of the compound to HIV-1 particles. In the present study, we dissected the individual and combinatorial contribut...

  9. Block copolymer battery separator

    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.

  10. Concord Housing Blocks

    Kumaraswamy, Mohan

    2002-01-01

    One element of the CIVCAL project Web-based resources containing images, tables, texts and associated data on the construction of Concord type Housing Blocks. A high rise public housing project using prefabriction and advanced formwork systems. Both Harmony and Concord Blocks are designed on the basis of standard modular flats which permit the use of factory produced components and a construction sequence which makes extensive use of advanced formwork systems.

  11. Efficient Block Truncation Coding

    K.Somasundaram,

    2010-09-01

    Full Text Available Block Truncation Coding (BTC is one of the lossy image compression techniques. The computational complexity involved in this method is very simple. In the proposed method, the feature of inter-pixel correlation is exploited to further reduce the requirement of bits to store a block. The proposed method gives very good performance in terms of bit-rate and PSNR values when compared to the conventional BTC.

  12. Blocking in Category Learning

    Bott, Lewis; Hoffman, Aaron B.; Murphy, Gregory L.

    2007-01-01

    Many theories of category learning assume that learning is driven by a need to minimize classification error. When there is no classification error, therefore, learning of individual features should be negligible. We tested this hypothesis by conducting three category learning experiments adapted from an associative learning blocking paradigm. Contrary to an error-driven account of learning, participants learned a wide range of information when they learned about categories, and blocking effe...

  13. The Chinese herb-derived Sparstolonin B suppresses HIV-1 transcription

    Deng, Xin; Zhang, Yaping (Lucy); Jiang, Feng; Chen, Ran; Peng, Peichun; Wen, Bin; Liang, Jian

    2015-01-01

    Background The Chines herb derived Sparstolonin B, (SsnB), is a recently identified natural compound that selectively blocks TLR2- and TLR4-mediated inflammatory signaling. But it is unknown whether this compound has any effect on HIV infection. Findings We found that SsnB treatment blocked HIV-1 transcription via a novel mechanism that requires the TAR region. Treatment of human T cell lines or peripheral blood mononuclear cells with SsnB at 1 μM significantly inhibited HIV production. Lastl...

  14. Hepatitis B and HIV

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  15. Children and HIV

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  16. Hepatitis A and HIV

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  17. HIV Treatment Adherence

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  18. Stages of HIV Infection

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  19. Hepatitis C and HIV

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ...

  20. Testing for HIV

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability (Biologics) HIV Home Test Kits Testing for HIV Share Tweet Linkedin Pin it More ...

  1. Smoking and HIV

    ... 28, 2014 Select a Language: Fact Sheet 803 Smoking and HIV WHY IS SMOKING MORE DANGEROUS FOR ... It can also worsen liver problems like hepatitis. Smoking and Side Effects People with HIV who smoke ...

  2. HIV/AIDS Basics

    ... Providers Prevention Resources Newsletter 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 ...

  3. Pregnancy and HIV

    ... 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 Resistance Testing

    ... 14, 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE ... ARVs. If you miss doses of your medications, HIV will multiply more easily. More mutations will occur. ...

  5. Exercise and HIV

    ... HIV WHY IS EXERCISE IMPORTANT? WHAT ARE THE ADVANTAGES OF EXERCISE? WHAT ARE THE RISKS OF EXERCISE? ... healthier while ageing with HIV. WHAT ARE THE ADVANTAGES OF EXERCISE? Regular, moderate exercise has many of ...

  6. Periodontitis in HIV patients

    Oseeva А.О.; Soboleva L.A.; Bulkina N.V.; Shuldyakov A.A.

    2011-01-01

    The article presents the study of formation mechanisms and periodontitis course in patients with subclinical stage of HIV-infection. The examination of 45 patients has enabled the division of patients into three basic groups: patients with periodontitis and HIV-infection; patients with periodontitis; and HIV patients without periodontitis. It has been determined that the patients with periodontitis and subclinical HIV-infection have developed local inflammatory reaction with infection, activa...

  7. Caging the Beast: TRIM5α Binding to the HIV-1 Core

    Felipe Diaz-Griffero

    2011-01-01

    The potent HIV-1 inhibitor TRIM5α blocks HIV-1 infection by accelerating the uncoating of HIV-1. TRIM5α is known to form higher-order self-association complexes that contribute to the avidity of TRIM5α for the HIV-1 capsid, and are essential to inhibit infection; these higher-order self-association complexes are dependent upon an intact B-box 2 domain. Even though the ability to form higher-order self-association complexes resembles the clathrin triskelion that forms a protein array, or cage,...

  8. Centrosomal pre-integration latency of HIV-1 in quiescent cells

    Emiliani Stéphane

    2007-09-01

    Full Text Available Abstract Human immunodeficiency virus type 1 (HIV-1 efficiently replicates in dividing and non-dividing cells. However, HIV-1 infection is blocked at an early post-entry step in quiescent CD4+ T cells in vitro. The molecular basis of this restriction is still poorly understood. Here, we show that in quiescent cells, incoming HIV-1 sub-viral complexes concentrate and stably reside at the centrosome for several weeks. Upon cell activation, viral replication resumes leading to viral gene expression. Thus, HIV-1 can persist in quiescent cells as a stable, centrosome-associated, pre-integration intermediate.

  9. HIV and AIDS

    ... are at greater risk for getting HIV during sex with infected partners. If a woman with HIV is pregnant, her newborn baby can catch the virus from her before birth, during the birthing process, or from breastfeeding. When doctors know a mom-to-be has HIV, they can do things ...

  10. Uniaxial backfill block compaction

    The main parts of the project were: to make a literature survey of the previous uniaxial compaction experiments; do uniaxial compaction tests in laboratory scale; and do industrial scale production tests. Object of the project was to sort out the different factors affecting the quality assurance chain of the backfill block uniaxial production and solve a material sticking to mould problem which appeared during manufacturing the blocks of bentonite and cruched rock mixture. The effect of mineralogical and chemical composition on the long term functionality of the backfill was excluded from the project. However, the used smectite-rich clays have been tested for mineralogical consistency. These tests were done in B and Tech OY according their SOPs. The objective of the Laboratory scale tests was to find right material- and compaction parameters for the industrial scale tests. Direct comparison between the laboratory scale tests and industrial scale tests is not possible because the mould geometry and compaction speed has a big influence for the compaction process. For this reason the selected material parameters were also affected by the previous compaction experiments. The industrial scale tests were done in summer of 2010 in southern Sweden. Blocks were done with uniaxial compaction. A 40 tons of the mixture of bentonite and crushed rock blocks and almost 50 tons of Friedland-clay blocks were compacted. (orig.)

  11. Impression block with orientator

    Tool review, namely the impression block, applied to check the shape and size of the top of fish as well as to determine the appropriate tool for fishing operation was realized. For multiple application and obtaining of the impress depth of 3 cm and more, the standard volumetric impression blocks with fix rods are used. However, the registered impress of fish is not oriented in space and the rods during fishing are in the extended position. This leads to rods deformation and sinking due to accidental impacts of impression block over the borehole irregularity and finally results in faulty detection of the top end of fishing object in hole. The impression blocks with copy rods and fixed magnetic needle allow estimating the object configuration and fix the position of magnetic needle determining the position of the top end of object in hole. However, the magnetic needle fixation is realized in staged and the rods are in extended position during fishing operations as well as it is in standard design. The most efficient tool is the impression block with copy rods which directs the examined object in the borehole during readings of magnetic needles data from azimuth plate and averaging of readings. This significantly increases the accuracy of fishing toll direction. The rods during fishing are located in the body and extended only when they reach the top of fishing object

  12. Block diagonal and schur complement preconditioners for block-toeplitz systems with small size blocks

    Ching, WK; Ng, MK; Wen, YW

    2007-01-01

    In this paper we consider the solution of Hermitian positive definite block-Toeplitz systems with small size blocks. We propose and study block diagonal and Schur complement preconditioners for such block-Toeplitz matrices. We show that for some block-Toeplitz matrices, the spectra of the preconditioned matrices are uniformly bounded except for a fixed number of outliers where this fixed number depends only on the size of the block. Hence, conjugate gradient type methods, when applied to solv...

  13. Nymble Blocking System

    Anand Joshi

    2012-05-01

    Full Text Available In order to allow users to access Internet services privately, anonymizing networks like Tor uses a series of routers to hide the client’s IP address from the server. These networks, however, have been marred by users employing this anonymity for abusive purposes such as defacing popular web sites. Usually, web site administrators rely on IP-address blocking in order to disable access to misbehaving users, but it is impractical if the abuser routes through an anonymizing network. In order to avoid this, administrators bar all known exit nodes of the anonymizing network, thereby denying anonymous access to all the users(whether misbehaving or not. To solve this issue, we introduce Nymble, a system where servers blacklist misbehaving users, thereby blocking users without affecting their anonymity. Nymble is thus agnostic to varied definitions of misbehavior. Servers can block users for any reason, and the privacy of blacklisted users is not affected in any case.

  14. Pin1 liberates the human immunodeficiency virus type-1 (HIV-1): Must we stop it?

    Hou, Hai; Wang, Jing-Zhang; Liu, Bao-Guo; Zhang, Ting

    2015-07-01

    Acquired immune deficiency syndrome (AIDS) is mainly caused by the human immunodeficiency virus type-1 (HIV-1). To our knowledge, this is the first review focusing on the vital role of Pin1 in the infection of HIV-1 and the development of AIDS. We and others have demonstrated that Pin1, the only known cis-to-trans isomerase recognizing the pThr/pSer-Pro motifs in proteins, plays striking roles in several human diseases. Interestingly, recent evidence gradually indicates that Pin1 regulates several key steps of the life cycle of HIV-1, including the uncoating of the HIV-1 core, the reverse transcription of the RNA genome of HIV-1, and the integration of the HIV-1 cDNA into human chromosomes. Whereas inhibiting Pin1 suppresses all of these key steps and attenuates the replication of HIV-1, at the same time different PIN1 gene variants are correlated with the susceptibility to HIV-1 infection. Furthermore, Pin1 potentially promotes HIV-1 infection by activating multiple oncogenes and inactivating multiple tumor suppressors, extending the life span of HIV-infected cells. These descriptions suggest Pin1 as a promising therapeutic target for the prevention of HIV-1 and highlight the possibility of blocking the development of AIDS by Pin1 inhibitors. PMID:25913034

  15. Bactericidal block copolymer micelles.

    Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo

    2011-05-12

    Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS-b-PAA and PS-b-P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.-%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution. PMID:21275041

  16. Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2.

    Furuya, Andrea Kinga Marias; Sharifi, Hamayun J; Jellinger, Robert M; Cristofano, Paul; Shi, Binshan; de Noronha, Carlos M C

    2016-04-01

    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. PMID:27093399

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

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    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 transfer...

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

    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. Tuberculosis and HIV Coinfection.

    Bruchfeld, Judith; Correia-Neves, Margarida; Källenius, Gunilla

    2015-07-01

    Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) constitute the main burden of infectious disease in resource-limited countries. In the individual host, the two pathogens, Mycobacterium tuberculosis and HIV, potentiate one another, accelerating the deterioration of immunological functions. In high-burden settings, HIV coinfection is the most important risk factor for developing active TB, which increases the susceptibility to primary infection or reinfection and also the risk of TB reactivation for patients with latent TB. M. tuberculosis infection also has a negative impact on the immune response to HIV, accelerating the progression from HIV infection to AIDS. The clinical management of HIV-associated TB includes the integration of effective anti-TB treatment, use of concurrent antiretroviral therapy (ART), prevention of HIV-related comorbidities, management of drug cytotoxicity, and prevention/treatment of immune reconstitution inflammatory syndrome (IRIS). PMID:25722472

  20. HIV Medicines and Side Effects

    Side Effects of HIV Medicines HIV Medicines and Side Effects (Last updated 1/7/2016; last reviewed 1/7/2016) 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 ...

  1. Spice Blocks Melanoma Growth

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  2. Contaminated soil concrete blocks

    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

  3. Effects of Block Scheduling

    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.

  4. Guatemalan plants extracts as virucides against HIV-1 infection.

    Bedoya, Luis M; Alvarez, Amparo; Bermejo, Mercedes; González, Nuria; Beltrán, Manuela; Sánchez-Palomino, Sonsoles; Cruz, Sully M; Gaitán, Isabel; del Olmo, Esther; Escarcena, Ricardo; García, Pablo A; Cáceres, Armando; San Feliciano, Arturo; Alcamí, José

    2008-06-01

    Prevention methods to avoid transmission of pathogens, including HIV, are crucial in the control of infectious diseases, not only to block epidemic spread but to avoid long-term treatments leading to emergence of resistances and drug associated side effects. Together with vaccine development, the discovery of new virucidal agents represents a research priority in this setting. In the screening of new compounds with antiviral activity, three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a classic antiviral assay and were found to inhibit HIV replication. This activity was corroborated by an original recombinant virus assay, leading us to perform a deeper study of the virucidal activity. Active fractions were non-toxic in vitro and also inhibited other enveloped viruses. Moreover, these fractions were able to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that represents the main way of HIV spread in vivo. PMID:18068962

  5. Fermion-Scalar Conformal Blocks

    Iliesiu, Luca; Poland, David; Pufu, Silviu S; Simmons-Duffin, David; Yacoby, Ran

    2015-01-01

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called `seed blocks' in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  6. Edit Distance with Block Deletions

    Dana Shapira; Storer, James A.

    2011-01-01

    Several variants of the edit distance problem with block deletions are considered. Polynomial time optimal algorithms are presented for the edit distance with block deletions allowing character insertions and character moves, but without block moves. We show that the edit distance with block moves and block deletions is NP-complete (Nondeterministic Polynomial time problems in which any given solution to such problem can be verified in polynomial time, and any NP problem can be converted into...

  7. Relationship between HIV protease inhibitors and QTc interval duration in HIV-infected patients: a cross-sectional study

    Charbit, Beny; Rosier, Arnaud; Bollens, Diane; Boccara, Franck; Boelle, Pierre-Yves; Koubaa, Afef; Girard, Pierre-Marie; Funck-Brentano, Christian

    2009-01-01

    AIMS QTc interval prolongation and torsades de pointes have been reported in HIV-infected patients. Protease inhibitors (PIs) are suspected to contribute to this adverse reaction. However, many factors can prolong QTc interval. We examined factors influencing QTc duration in HIV-infected patients. METHODS Unselected HIV-infected patients (n = 978) were enrolled in this prospective, single-centre cross-sectional study. Variables related to infection and treatments were collected. A digital electrocardiographic record was recorded in each patient and QT interval duration was measured and corrected using both Bazett's (QTcB) and Fridericia's (QTcF) formula. Results were analysed with a multivariable linear model. RESULTS After excluding arrhythmias and complete bundle branch blocks, QT interval was measured in 956 patients. The mean (SD) QTcB was 418 ms (23) and QTcF was 405 ms (20). QTc was found prolonged (>450 ms in women and >440 ms in men) in 129 [13.5%; 95% confidence interval (CI) 11.5, 15.8] and 38 (4%; 95% CI 2.9, 5.4) patients using Bazett and Fridericia corrections, respectively. On multivariable analysis, incomplete bundle branch block, ventricular hypertrophy, signs of ischaemic cardiopathy, female gender, White ethnic origin and age were significantly associated with QTc prolongation. The only HIV variable independently associated with QTc prolongation was the duration of infection (P = 0.023). After adjustment, anti-HIV treatment, in particular PI (P = 0.99), was not associated with QTc prolongation. CONCLUSIONS Although PIs block in vitro hERG current, they are not independently associated with QTc interval prolongation. Prolonged QTc interval in HIV-infected patients is primarily associated with factors commonly known to prolong QT and with the duration of HIV infection. PMID:19076152

  8. Interactive Effects of Cocaine on HIV Infection: Implication in HIV-Associated Neurocognitive Disorder and NeuroAIDS

    Santosh eDahal

    2015-09-01

    Full Text Available Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV, but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine in the brain, by blocking the dopamine transporters (DAT which is critical for dopamine homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to dopamine, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs, which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND. HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the Blood Brain Barrier (BBB in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies

  9. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

    Dahal, Santosh; Chitti, Sai V P; Nair, Madhavan P N; Saxena, Shailendra K

    2015-01-01

    Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection

  10. Past, present, and future of entry inhibitors as HIV microbicides.

    Gibson, Richard M; Arts, Eric J

    2012-01-01

    Preventing the transmission of human immunodeficiency virus (HIV) is the main goal of numerous studies trying to develop an effective vaccine and microbicide agents. Here we review the use of antiretroviral drugs to inhibit viral entry as potential HIV microbicides. After the failure of nonoxynol-9 microbicide strategies shifted towards the use of compounds creating a physical barrier to virus attachment (e.g., surfactants) or inhibit the virus in the vaginal milieu (e.g., polyanions). These early, non-specific inhibitors showed promise in both in vitro and in vivo(non-human primates) studies but provided only modest protection from HIV transmission in clinical efficacy trials. The next generation of HIV entry microbicides was based on specifically blocking virus from entering host cells by targeting CD4 attachment, gp120 binding, and virus-cell membrane fusion events. Although protection from an SIV-HIV hybrid was evident in non-human primates treated and challenged in the vaginal cavity, none of these compounds have advanced to clinical trials as a microbicide. Here we will discuss the reasons for these failures, including the selection of drug resistant HIV variants, which raises questions as to the future of broadly effective microbicides based on HIV entry inhibitors. The outcome of continued research and potential efficacy trials on the next generation of entry inhibitors might reveal whether or not an effective entry microbicide can be developed. PMID:22264042

  11. 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

    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.

  12. Drugs + HIV, Learn the Link

    Full Text Available ... Global Health Hepatitis (Viral) HIV/AIDS Medical Consequences Mental Health Military Pain Prevention Treatment Trends & Statistics Women ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, National Center for HIV, STD, and ...

  13. HIV / AIDS: An Unequal Burden

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 Table ... Victoria Cargill talks to students about HIV and AIDS at the opening of a National Library of ...

  14. HIV, AIDS, and the Future

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 Table ... and your loved ones from HIV/AIDS. The AIDS Memorial Quilt In 1987, a total of 1, ...

  15. Drugs + HIV, Learn the Link

    Full Text Available ... and Prevention, National Center for HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/ ... of HIV in brain cells 1 . Drug abuse treatment. Since the late 1980s, research has shown that ...

  16. Drugs + HIV, Learn the Link

    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 ...

  17. Drugs + HIV, Learn the Link

    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 ...

  18. HIV/AIDS and Alcohol

    ... 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, ...

  19. HIV, AIDS, and the Future

    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 ...

  20. Drugs + HIV, Learn the Link

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and ...

  1. Drugs + HIV, Learn the Link

    Full Text Available ... abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to cells ... do not abuse drugs. In animal studies, methamphetamine has been shown to increase the amount of HIV ...

  2. Drugs + HIV, Learn the Link

    Full Text Available ... chances of unsafe behavior by altering judgment and decision-making. To learn about HIV among youth, please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/ ...

  3. Drugs + HIV, Learn the Link

    Full Text Available ... Education Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter ... research findings and news updates. Read on to Learn the Link between drug abuse and HIV and ...

  4. HIV-Positive-to-HIV-Positive Liver Transplantation.

    Calmy, A; van Delden, C; Giostra, E; Junet, C; Rubbia Brandt, L; Yerly, S; Chave, J-P; Samer, C; Elkrief, L; Vionnet, J; Berney, T

    2016-08-01

    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 multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients. PMID:27109874

  5. The CD85j+ NK cell subset potently controls HIV-1 replication in autologous dendritic cells.

    Daniel Scott-Algara

    Full Text Available Natural killer (NK cells and dendritic cells (DC are thought to play critical roles in the first phases of HIV infection. In this study, we examined changes in the NK cell repertoire and functions occurring in response to early interaction with HIV-infected DC, using an autologous in vitro NK/DC coculture system. We show that NK cell interaction with HIV-1-infected autologous monocyte-derived DC (MDDC modulates NK receptor expression. In particular, expression of the CD85j receptor on NK cells was strongly down-regulated upon coculture with HIV-1-infected MDDC. We demonstrate that CD85j(+ NK cells exert potent control of HIV-1 replication in single-round and productively HIV-1-infected MDDC, whereas CD85j(- NK cells induce a modest and transient decrease of HIV-1 replication. HIV-1 suppression in MDCC by CD85j(+ NK cells required cell-to-cell contact and did not appear mediated by cytotoxicity or by soluble factors. HIV-1 inhibition was abolished when NK-MDDC interaction through the CD85j receptor was blocked with a recombinant CD85j molecule, whereas inhibition was only slightly counteracted by blocking HLA class I molecules, which are known CD85j ligands. After masking HLA class I molecules with specific antibodies, a fraction of HIV-1 infected MDDC was still strongly stained by a recombinant CD85j protein. These results suggest that CD85j(+ NK cell inhibition of HIV-1 replication in MDDC is mainly mediated by CD85j interaction with an unknown ligand (distinct from HLA class I molecules preferentially expressed on HIV-1-infected MDDC.

  6. Right bundle branch block

    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 in...... men vs. 0.5%/2.3% in women, P <0.001). Significant predictors of newly acquired RBBB were male gender, increasing age, high systolic blood pressure, and presence of IRBBB, whereas predictors of newly acquired IRBBB were male gender, increasing age, and low BMI. 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...

  7. NCCN Evidence Blocks.

    Carlson, Robert W; Jonasch, Eric

    2016-05-01

    NCCN has developed a series of Evidence Blocks: graphics that provide ratings for each recommended treatment regimen in terms of efficacy, toxicity, quality and consistency of the supporting data, and affordability. The NCCN Evidence Blocks are currently available in 10 tumor types within the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). At a glance, patients and providers can understand how a given treatment was assessed by the NCCN Guidelines Panel and get a sense of how a given treatment may match individual needs and preferences. Robert W. Carlson, MD, CEO of NCCN, described the reasoning behind this new feature and how the tool is used, and Eric Jonasch, MD, Professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and Vice Chair of the NCCN Kidney Cancer Panel, described its applicability in the management of metastatic renal cell carcinoma. PMID:27226499

  8. SNUPPS power block modelling

    A series of models is being built and used as tools in the design of the SNUPPS Standard Power Block. The modelling programme includes both preliminary and final design models, a construction sequence mode, and additional models used to study various features of the design. The design of a standard power block unit has necessitated design definition which is more detailed than that customarily used in the design of nuclear power stations. One innovation is the use of engineering models as a primary design tool in the layout of process piping, preparation of isometric drawings, design of small components which are customarily designed in the field during construction. Development of a standard construction sequence and construction work plan is another innovation. (author)

  9. Growth, Endlessness, Blocks

    Nabata, Avery Misuzu

    2014-01-01

    Growth, Endlessness, Blocks is a sculptural installation comprised of a series of wood structures of various scales. Large sections of drywall function as extensions of the gallery walls. Each structure balances a number of different physical characteristics that are tied to the act of making. Balance and presence combine in a disconcerting way giving the viewer a sense of uneasiness and a moment finely tuned by the artist. The artist seeks to embody the role of the factory fabricator as a me...

  10. SUPERFICIAL CERVICAL PLEXUS BLOCK

    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.

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

    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. Travelling with HIV

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

    2014-01-01

    BACKGROUND: We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals. METHODS: During a six-month period a questionnaire was handed out to 2821 adult HIV-infected individuals attending any of the...... eight Danish medical HIV care centers. RESULTS: A total of 763 individuals responded. During the previous two years 49% had travelled outside Europe; 18% had travelled less and 30% were more cautious when choosing travel destination than before the HIV diagnosis. Pre-travel advice was sought by only 38......%, and travel insurance was taken out by 86%. However, 29%/74% did not inform the advisor/the insurance company about their HIV status. Nearly all patients on highly active antiretroviral therapy (HAART) were adherent, but 58% worried about carrying HIV-medicine and 19% tried to hide it. Only 19...

  13. HIV Stigma Among Substance Abusing People Living with HIV/AIDS: Implications for HIV Treatment

    Levi-Minzi, Maria A.; Hilary L Surratt

    2014-01-01

    HIV-related stigma has a major impact on quality of life and health among people living with HIV and AIDS (PLWHA). This study examines demographic, mental health, behavioral, contextual, and HIV care-related correlates of HIV stigma among 503 substance abusing PLWHA. Stigma was measured with the HIV Internalized Stigma Measure which has four subscales: stereotypes about HIV, self-acceptance, disclosure concerns, and social relationships. Severe substance dependence (55.3%) and depression (54....

  14. HIV and Fertility Revisited

    Sebnem Kalemli-Ozcan; Belgi Turan

    2010-01-01

    Young (2005) argues that HIV related population declines reinforced by the fertility response to the epidemic will lead to higher capital-labor ratios and to higher per capita incomes in the affected countries of Africa. Using household level data on fertility from South Africa and relying on between cohort variation in country level HIV infection, he estimates a large negative effect of HIV prevalence on fertility. However, the studies that utilize the recent rounds of Demographic Health Sur...

  15. Microbiome in HIV infection

    Salas, January T; Chang, Theresa L

    2014-01-01

    HIV primary infection occurs at mucosa tissues, suggesting an intricate interplay between microbiome and HIV infection. Recent advanced technologies of high-throughput sequencing and bioinformatics allow researchers to explore nonculturable microbes including bacteria, virus and fungi and their association with diseases. HIV/SIV infection is associated with microbiome shifts and immune activation that may affect the outcome of disease progression. Similarly, altered microbiome and inflammatio...

  16. Revisiting HIV-1 uncoating

    Arhel Nathalie

    2010-01-01

    Abstract HIV uncoating is defined as the loss of viral capsid that occurs within the cytoplasm of infected cells before entry of the viral genome into the nucleus. It is an obligatory step of HIV-1 early infection and accompanies the transition between reverse transcription complexes (RTCs), in which reverse transcription occurs, and pre-integration complexes (PICs), which are competent to integrate into the host genome. The study of the nature and timing of HIV-1 uncoating has been paved wit...

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

    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

  18. Novel 3′-Processing Integrase Activity Assay by Real-Time PCR for Screening and Identification of HIV-1 Integrase Inhibitors

    Supachai Sakkhachornphop; Weeraya Thongkum; Chatchai Tayapiwatana

    2015-01-01

    The 3′-end processing (3′P) of each viral long terminal repeat (LTR) during human immunodeficiency virus type-1 (HIV-1) integration is a vital step in the HIV life cycle. Blocking the 3′P using 3′P inhibitor has recently become an attractive strategy for HIV-1 therapeutic intervention. Recently, we have developed a novel real-time PCR based assay for the detection of 3′P activity in vitro. The methodology usually involves biotinylated HIV-1 LTR, HIV-1 integrase (IN), and specific primers and ...

  19. Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo

    Sassi, Atfa; Brichacek, Beda; Hieny, Sara; Yarovinsky, Felix; Golding, Hana; Grivel, Jean-Charles; Sher, Alan; Margolis, Leonid

    2016-01-01

    Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii -encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants. PMID:19671446

  20. Demographic Data - MDC_Block

    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...

  1. Ear - blocked at high altitudes

    High altitudes and blocked ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... you are going up or coming down from high altitudes. Chewing gum the entire time you are changing ...

  2. CCR5 inhibitors: Emerging promising HIV therapeutic strategy

    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

  3. Porous block nanofiber composite filters

    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).

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

    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.

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

    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.

  6. SCREENING OF HOSPITAL PATIENTS FOR HIV: AN EXPERIENCE TERTIARY CARE HOSPITAL OF BIDAR DISTRICT

    Vijay Kumar

    2014-08-01

    Full Text Available OBJECTIVE: The clinical consequences of HIV infection encompass a wide spectrum. The Early recognition of persons who have HIV will help in early interventions to halt or slow the progress of HIV disease and to extend fruitful lives. METHODOLOGY: This cross-sectional study was conducted among patient referred to the voluntary counseling and testing center (VCTC from various departments in, BRIMS Teaching Hospital, Taluka Hospital, Humnabad, Taluka Hospital, Basavakalyan, Taluka Hospital Aurad and Taluka Hospital Bhalki, to find out the pattern of disease/ symptoms high risk behaviors (HRB for HIV and HIV serostatus among the hospital patients. Following the guidelines prescribed by the National AIDS Control Organization (NACO anonymous data were collected through interview from 500 individuals. Where a specific diagnosis of a disease was obtained mutually exclusive symptoms were considered for analysis. RESULTS: The major diseases/ symptoms observed among those patients were tuberculosis in 32.19%, STD in 29.97% prolonged explained fever in 19.41 of the patients. The overall rate of HIV seroreactivity was 17.44%. The HIV serostaus by diseases/ symptoms showed that 32.91% of patients with prolonged unexplained fever were HIV seroreacive; the rate was 12.90% among patients with skin diseases, 12.29% in STD and 12.21 in tuberculosis patients. Overall, 332 patients (66.34% had HRD for HIA/ AIDS. The rate of HIV seroreactivity was more among patients who had HRB for HIV/ AIDS and who were referred from indoor departments (23.24% compared to outdoor departments (13.65%. The patients suffering from prolonged unexplained fever need greater attention fro HIV screening. CONCLUSION: Early detection of HIV positive patients makes interventions possible at a very early stage and this can slow down/ block the progress of HIV disease and as a result can extend fruitful life

  7. A standard graphite block

    A graphite block was calibrated for the thermal neutron flux of the Ra-Be source using indium foils as detectors. Experimental values of the thermal neutron flux along the central vertical axis of the system were corrected for the self-shielding effect and depression of flux in the detector. The experimental values obtained were compared with the values calculated on the basis of solving the conservation neutron equation by the continuous slowing-down theory. In this theoretical calculation of the flux the Ra-Be source was divided into three resonance energy regions. The measurement of the thermal neutron diffusion length in the standard graphite block is described. The measurements were performed in the thermal neutron region of the system. The experimental results were interpreted by the diffusion theory for point thermal neutron source in the finite system. The thermal neutron diffusion length was calculated to be L= 50.9 ±3.1 cm for the following graphite characteristics: density = 1.7 g/cm3; boron content = 0.1 ppm; absorption cross section = 3.7 mb

  8. One-Block CYRCA: an automated procedure for identifying multiple-block alignments from single block queries

    Frenkel-Morgenstern, Milana; Singer, Alice; Bronfeld, Hagit; Pietrokovski, Shmuel

    2005-01-01

    One-Block CYRCA is an automated procedure for identifying multiple-block alignments from single block queries (). It is based on the LAMA and CYRCA block-to-block alignment methods. The procedure identifies whether the query blocks can form new multiple-block alignments (block sets) with blocks from a database or join pre-existing database block sets. Using pre-computed LAMA block alignments and CYRCA sets from the Blocks database reduces the computation time. LAMA and CYRCA are highly sensit...

  9. Escape from Human Immunodeficiency Virus Type 1 (HIV-1 Entry Inhibitors

    Carol D. Weiss

    2012-12-01

    Full Text Available The human immunodeficiency virus (HIV enters cells through a series of molecular interactions between the HIV envelope protein and cellular receptors, thus providing many opportunities to block infection. Entry inhibitors are currently being used in the clinic, and many more are under development. Unfortunately, as is the case for other classes of antiretroviral drugs that target later steps in the viral life cycle, HIV can become resistant to entry inhibitors. In contrast to inhibitors that block viral enzymes in intracellular compartments, entry inhibitors interfere with the function of the highly variable envelope glycoprotein as it continuously adapts to changing immune pressure and available target cells in the extracellular environment. Consequently, pathways and mechanisms of resistance for entry inhibitors are varied and often involve mutations across the envelope gene. This review provides a broad overview of entry inhibitor resistance mechanisms that inform our understanding of HIV entry and the design of new inhibitors and vaccines.

  10. HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway.

    Ji, Jiaxiang; Sahu, Gautam K; Braciale, Vivian L; Cloyd, Miles W

    2005-06-01

    In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14(+) monocytes infected by either HIV-1(213) (X4) or HIV-1(BaL) (R5) produced IL-10, IL-6, tumor necrosis factor-alpha (TNF-alpha), and to a lesser extent, IFN-gamma. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14(+) monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-alpha and IFN-gamma but no IL-10 production by CD14(+) monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1(213), HIV-1(BaL) or HIV-1 gp160 in CD14(+) monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1(213) could induce IL-10 mRNA expression in CD14(+) monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1(213)-induced IL-10 mRNA expression in CD14(+) monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14(+) monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection. PMID:15937058

  11. Drugs + HIV, Learn the Link

    Full Text Available ... the link between drug abuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ... 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 ...

  12. Living with HIV/AIDS

    Infection with HIV is serious. But the outlook for people with HIV/AIDS is improving. If you are infected with HIV, there are many things you can do to ... health care provider who knows how to treat HIV. You may want to join a support group. ...

  13. HIV/AIDS and Alcohol

    ... Other Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and abuse can contribute to the spread of HIV/AIDS and affect treatment for infected patients. Abusing alcohol ...

  14. Drugs + HIV, Learn the Link

    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 ...

  15. Indikatorsygdomme for hiv-infektion

    Hansen, Birgitte Rønde; Andersen, Åse Bengård; Koch, Anders; Ravn, Pernille; Larsen, Carsten Schade; Weis, Nina; Gerstoft, Jan

    2015-01-01

    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....

  16. Ludacris Talks About HIV

    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.

  17. Let's Stop HIV Together

    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.

  18. HIV/AIDS

    ... health days Meetings and consultations 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts HIV/AIDS Fact sheet Updated July 2016 Key facts HIV continues to be a major global public health issue, having claimed more than 35 million lives so far. In 2015, 1.1 (940 000– ...

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

    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.

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

    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.

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

    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. PMID:27182834

  2. Indikatorsygdomme for hiv-infektion

    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....

  3. HIV and neurocognitive dysfunction.

    Spudich, Serena

    2013-09-01

    The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART. PMID:23860944

  4. HIV-Associated Tuberculosis.

    Naidoo, Kogieleum; Naidoo, Kasavan; Padayatchi, Nesri; Abdool Karim, Quarraisha

    2011-01-01

    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. PMID:20871843

  5. Periodontitis in HIV patients

    Oseeva А.О.

    2011-09-01

    Full Text Available The article presents the study of formation mechanisms and periodontitis course in patients with subclinical stage of HIV-infection. The examination of 45 patients has enabled the division of patients into three basic groups: patients with periodontitis and HIV-infection; patients with periodontitis; and HIV patients without periodontitis. It has been determined that the patients with periodontitis and subclinical HIV-infection have developed local inflammatory reaction with infection, activation of anti-inflammatory cytokines in parodontal recess fluid. It has been proved that the causative factor of frequent and durable relapses in parodontal pathology with clinical HIV-infection was the development of pathologic process with endotoxicosis syndrome and imbalance of lipid peroxidation and antioxidant system

  6. Mucosal HIV-1 transmission and prevention strategies in BLT humanized mice

    Denton, Paul W.; Garcia, J. Victor

    2012-01-01

    Clinical trials testing microbicides and related biomedical interventions to block HIV transmissions have produced contradictory results and to date it is unclear why. Further elucidation of the molecular basis of mucosal HIV transmission and extensive pharmacokinetic and pharmacodynamic analyses are essential to implementing effective prevention strategies. Animal models are of critical importance to this effort and bone marrow-liver-thymus (or BLT) humanized mice have recently emerged as a ...

  7. Porphyromonas gingivalis induces CCR5-dependent transfer of infectious HIV-1 from oral keratinocytes to permissive cells

    Dietrich Elizabeth A

    2008-03-01

    Full Text Available Abstract Background Systemic infection with HIV occurs infrequently through the oral route. The frequency of occurrence may be increased by concomitant bacterial infection of the oral tissues, since co-infection and inflammation of some cell types increases HIV-1 replication. A putative periodontal pathogen, Porphyromonas gingivalis selectively up-regulates expression of the HIV-1 coreceptor CCR5 on oral keratinocytes. We, therefore, hypothesized that P. gingivalis modulates the outcome of HIV infection in oral epithelial cells. Results Oral and tonsil epithelial cells were pre-incubated with P. gingivalis, and inoculated with either an X4- or R5-type HIV-1. Between 6 and 48 hours post-inoculation, P. gingivalis selectively increased the infectivity of R5-tropic HIV-1 from oral and tonsil keratinocytes; infectivity of X4-tropic HIV-1 remained unchanged. Oral keratinocytes appeared to harbor infectious HIV-1, with no evidence of productive infection. HIV-1 was harbored at highest levels during the first 6 hours after HIV exposure and decreased to barely detectable levels at 48 hours. HIV did not appear to co-localize with P. gingivalis, which increased selective R5-tropic HIV-1 trans infection from keratinocytes to permissive cells. When CCR5 was selectively blocked, HIV-1 trans infection was reduced. Conclusion P. gingivalis up-regulation of CCR5 increases trans infection of harbored R5-tropic HIV-1 from oral keratinocytes to permissive cells. Oral infections such as periodontitis may, therefore, increase risk for oral infection and dissemination of R5-tropic HIV-1.

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

    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

  9. Photovoltaic building blocks

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    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...... coating tools to depositand develop anti-reflection filters by means of sputtering or e-beam evaporation. To reduce the area taken up by metallic contacts transparent conducting oxides like Aluminium doped ZincOxide (AZO) and Indium Tin Oxide (ITO) can be deposited. We also support research...... and development of new 2D materials like graphene that is a promising candidate for cheap highly transparent contacts. Another way to increase efficiency is to structure the active layers indevice so that more light is absorbed. This can be done in one of our advanced dry etching machines either mask-less to form...

  10. Blocking the Hawking radiation

    Autzen, M.; Kouvaris, C.

    2014-01-01

    grows after its formation (and eventually destroys the star) instead of evaporating. The fate of the black hole is dictated by the two opposite mechanics, i.e., accretion of nuclear matter from the center of the star and Hawking radiation that tends to decrease the mass of the black hole. We study how......Some severe constraints on asymmetric dark matter are based on the scenario that certain types of weakly interacting massive particles can form mini-black holes inside neutron stars that can lead to their destruction. A crucial element for the realization of this scenario is that the black hole...... the assumptions for the accretion rate can in fact affect the critical mass beyond which a black hole always grows. We also study to what extent degenerate nuclear matter can impede Hawking radiation due to the fact that emitted particles can be Pauli blocked at the core of the star....

  11. Block Voter Model

    Sampaio, C I N

    2011-01-01

    We introduce and study the block voter model with noise on two-dimensional square lattices using Monte Carlo simulations and finite-size scaling techniques. The model is defined by an outflow dynamics where a central set of $N_{PCS}$ spins, here denoted by persuasive cluster spins (PCS), tries to influence the opinion of their neighbouring counterparts. We consider the collective behaviour of the entire system with varying PCS size. When $N_{PCS}>2$, the system exhibits an order-disorder phase transition at a critical noise parameter $q_{c}$ which is a monotonically increasing function of the size of the persuasive cluster. We conclude that how large the PCS is more power of persuasion it has. It also seems that the resulting critical behaviour is Ising-like independent of the range of the interactions.

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

    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.

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

    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.

  14. HIV treatment for prevention

    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

  15. HIV treatment for prevention.

    Ambrosioni, Juan; Calmy, Alexandra; Hirschel, Bernard

    2011-01-01

    "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 waves of testing would precisely

  16. The Block-block Bootstrap: Improved Asymptotic Refinements

    Donald W.K. Andrews

    2002-01-01

    The asymptotic refinements attributable to the block bootstrap for time series are not as large as those of the nonparametric iid bootstrap or the parametric bootstrap. One reason is that the independence between the blocks in the block bootstrap sample does not mimic the dependence structure of the original sample. This is the join-point problem. In this paper, we propose a method of solving this problem. The idea is not to alter the block bootstrap. Instead, we alter the original sample sta...

  17. Convergence rates of empirical block length selectors for block bootstrap

    Nordman, Daniel J.; Lahiri, Soumendra N.

    2014-01-01

    We investigate the accuracy of two general non-parametric methods for estimating optimal block lengths for block bootstraps with time series – the first proposed in the seminal paper of Hall, Horowitz and Jing (Biometrika 82 (1995) 561–574) and the second from Lahiri et al. (Stat. Methodol. 4 (2007) 292–321). The relative performances of these general methods have been unknown and, to provide a comparison, we focus on rates of convergence for these block length selectors for the moving block ...

  18. Large Block Test Final Report

    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

  19. Production of Interferons and β-Chemokines by Placental Trophoblasts of HIV-1-Infected Women

    Reuben, James M.; Shearer, William T; Mary Paul; Claudia Kozinetz; Stanley Cron; Popek, Edwina J; Hunter Hammill; Bang-Ning Lee

    2001-01-01

    Objective: The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the β-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-α (MIP-1α), and MIP-1β can block H...

  20. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus

    Hirotaka Ebina; Naoko Misawa; Yuka Kanemura; Yoshio Koyanagi

    2013-01-01

    Even though highly active anti-retroviral therapy is able to keep HIV-1 replication under control, the virus can lie in a dormant state within the host genome, known as a latent reservoir, and poses a threat to re-emerge at any time. However, novel technologies aimed at disrupting HIV-1 provirus may be capable of eradicating viral genomes from infected individuals. In this study, we showed the potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its expression. When LTR-targ...

  1. NOVEL DELIVERY SYSTEM ENHANCES EFFICACY OF ANTIRETROVIRAL THERAPY IN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS (HIVE)

    Spitzenberger, Timothy J.; Heilman, David; Diekmann, Casey; Batrakova, Elena; Kabanov, Alexander; Gendelman, Howard E.; Elmquist, William F.; Persidsky, Yuri

    2006-01-01

    Most potent anti-retroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of anti-retroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). SCID mice inoculated with HIV-1 infected human monocyt...

  2. MedlinePlus: HIV/AIDS Medicines

    ... Training Center) Also in Spanish Side Effects (New Mexico AIDS Education and Training Center) Also in Spanish Side Effects of HIV Medicines: HIV and Diabetes (AIDSinfo) Side Effects of HIV Medicines: HIV and ...

  3. Flazinamide, a novel β-carboline compound with anti-HIV actions

    A β-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-β-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38 μM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89 μM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77 μM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle

  4. HIV Molecular Immunology 2014

    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.

  5. Dimensional Reduction for Conformal Blocks

    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.

  6. Covariant Approaches to Superconformal Blocks

    Fitzpatrick, A Liam; Khandker, Zuhair U; Li, Daliang; Poland, David; Simmons-Duffin, David

    2014-01-01

    We develop techniques for computing superconformal blocks in 4d superconformal field theories. First we study the super-Casimir differential equation, deriving simple new expressions for superconformal blocks for 4-point functions containing chiral operators in theories with N-extended supersymmetry. We also reproduce these results by extending the "shadow formalism" of Ferrara, Gatto, Grillo, and Parisi to supersymmetric theories, where superconformal blocks can be represented as superspace integrals of three-point functions multiplied by shadow three-point functions.

  7. Control rod blocking device

    Purpose: To increase the degree of freedom for the reactor operation by control rod blocking by monitoring the critical power ratio (CPR) with real time. Constitution: There has been a problem that the withdrawal of control rods may occasionally be inhibited with all the margin in view of CPR. The present invention dissolves this problem. That is, the control rod withdrawal device periodically calculates CPR, and calculated CPR upon generation of a control rod withdrawing signal by conpensating the result of calculation with a LPRM signal and a reactor core flow rate signal. The CPR at real time is compared with a predetermined setting value to output a control rod withdrawing inhibition signal depending on the result of the comparison. In the device as described above, since CPR is monitored at real time, the control rod can be withdrawn without causing fuel damages, as well as the inhibition of withdrawal irrespective of the presence of margin in view of CPR can be avoided. Accordingly, degree of freedom in the reactor operation can be increased. (Kamimura, M.)

  8. HIV transmission biology: translation for HIV prevention.

    Ronen, Keshet; Sharma, Amit; Overbaugh, Julie

    2015-11-01

    Rigorous testing of new HIV-prevention strategies is a time-consuming and expensive undertaking. Thus, making well informed decisions on which candidate-prevention approaches are most likely to provide the most benefit is critical to appropriately prioritizing clinical testing. In the case of biological interventions, the decision to test a given prevention approach in human trials rests largely on evidence of protection in preclinical studies. The ability of preclinical studies to predict efficacy in humans may depend on how well the model recapitulates key biological features of HIV transmission relevant to the question at hand. Here, we review our current understanding of the biology of HIV transmission based on data from animal models, cell culture, and viral sequence analysis from human infection. We summarize studies of the bottleneck in viral transmission; the characteristics of transmitted viruses; the establishment of infection; and the contribution of cell-free and cell-associated virus. We seek to highlight the implications of HIV-transmission biology for development of prevention interventions, and to discuss the limitations of existing preclinical models. PMID:26418086

  9. HIV among Gay and Bisexual Men

    ... 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 ...

  10. Primaer HIV-infektion

    Pedersen, C; Pedersen, B K

    1996-01-01

    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...