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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

    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

  2. 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

  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. 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

  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

    =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

  8. 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 ...

  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. 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.

  4. 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 ...

  5. 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 ( ...

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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; ...

  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. 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 ...

  8. 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, ...

  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. 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 ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  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. 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...

  1. 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

  2. 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

  3. 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.

  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. 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.

  7. 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

  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. 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…

  16. 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...

  17. 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...

  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. 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...

  11. 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.

  12. 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.

  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. 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 ...

  15. 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 ...

  16. 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. ...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  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. 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

  11. 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.)

  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. 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...

  17. 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

  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. 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.

  2. 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…

  3. 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

  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. 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...

  6. 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.

  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. 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, ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. 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/ ...

  20. 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 ...

  1. 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 ...

  2. 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, ...

  3. 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 ...

  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. 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

  7. 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...

  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. 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.

  10. 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...

  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. 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...

  15. 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...

  16. 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...

  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. 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. ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  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. 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.

  17. 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– ...

  18. 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.

  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. 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

  4. 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

  5. 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

  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. 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....

  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. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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...

  15. 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 ...

  16. 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

  17. 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

  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. 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...

  20. 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...

  1. 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...

  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. 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.

  5. 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.

  6. 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.

  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. HIV among Transgender People

    ... mobilization, HIV testing, and coordinated referral networks and service integration). Developing Act Against AIDS communication materials to reach transgender people, including campaigns such as: Doing It , which ... & services . San Francisco, CA: University of California, San Francisco, ...

  11. 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...

  12. HIV and Kidney Disease

    ... Sheets Permission to Use Fact Sheets Sponsors and Advertising Privacy Policy Project ... Disease WHY SHOULD PEOPLE WITH HIV CARE ABOUT KIDNEY DISEASE? WHAT IS NORMAL KIDNEY FUNCTION? HOW DO I KNOW IF THERE ARE PROBLEMS ...

  13. HIV/AIDS

    ... Casual contact, such as hugging Mosquitoes Participating in sports Touching items that were touched by a person ... 20 years. People with AIDS have had their immune system damaged by HIV. They are at very high ...

  14. HIV Genotypic Resistance Testing

    ... of the disease progression and to minimize viral replication and mutation. However, a person may be initially infected with a drug-resistant HIV strain or drug resistance may develop during treatment, ...

  15. Drugs, Alcohol and HIV

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research (MIRECC) Military Exposures Polytrauma Rehabilitation Spinal Cord Injury Telehealth Womens Health Issues Wellness Programs MyHealtheVet Nutrition Quitting Smoking ...

  16. Mental Health and HIV

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research (MIRECC) Military Exposures Polytrauma Rehabilitation Spinal Cord Injury Telehealth Womens Health Issues Wellness Programs MyHealtheVet Nutrition Quitting Smoking ...

  17. Vaccinations and HIV

    ... 23, 2014 Select a Language: Fact Sheet 207 Vaccinations and HIV WHAT ARE VACCINATIONS? WHAT’S DIFFERENT FOR ... your viral load within 4 weeks of any vaccination. Flu shots have been studied more than any ...

  18. Caring for Children Affected by HIV and AIDS

    UNICEF Innocenti Research Centre

    2006-01-01

    This IRC Insight highlights the urgent need to support families and communities to care for children orphaned by HIV/AIDS. The report looks at how the epidemic undermines children's health and schooling, and reinforces marginalization and deprivation. It explores the options for the care of children in communities affected by the AIDS epidemic. Beginning with the premise that the parent-child bond is the basic building block of child development and the family the basic unit of society, the r...

  19. HIV Molecular Immunology 2015

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

    2016-04-05

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

  20. Four-block beam collimator

    1977-01-01

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

  1. Classical Virasoro irregular conformal block

    Rim, Chaiho

    2015-01-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  2. OPAL Various Lead Glass Blocks

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

  3. A patient carrying HIV

    Adeela, Bashir

    2009-01-01

    A 52-year-old Caucasian man presented to hospital with confusion and was treated for a urinary tract infection. He developed new and unexpected signs and symptoms during his stay in hospital. On further questioning, the story of his social background unfolded and, following further investigation, he was diagnosed with human immunodeficiency virus (HIV). This case reminds all clinicians to think about HIV in the older patient and it also gives direction for investigation and management of simi...

  4. The Shamrock lumbar plexus block

    Sauter, Axel R; Ullensvang, Kyrre; Niemi, Geir;

    2015-01-01

    BACKGROUND: The Shamrock technique is a new method for ultrasound-guided lumbar plexus blockade. Data on the optimal local anaesthetic dose are not available. OBJECTIVE: The objective of this study is to estimate the effective dose of ropivacaine 0.5% for a Shamrock lumbar plexus block. DESIGN: A...... prospective dose-finding study using Dixon's up-and-down sequential method. SETTING: University Hospital Orthopaedic Anaesthesia Unit. INTERVENTION: Shamrock lumbar plexus block performance and block assessment were scheduled preoperatively. Ropivacaine 0.5% was titrated with the Dixon and Massey up......-and-down method using a stepwise change of 5 ml in each consecutive patient. Combined blocks of the femoral, the lateral femoral cutaneous and the obturator nerve were prerequisite for a successful lumbar plexus block. PATIENTS: Thirty patients scheduled for lower limb orthopaedic surgery completed the study...

  5. On Approximability of Block Sorting

    Narayanaswamy, N S

    2011-01-01

    Block Sorting is a well studied problem, motivated by its applications in Optical Character Recognition (OCR), and Computational Biology. Block Sorting has been shown to be NP-Hard, and two separate polynomial time 2-approximation algorithms have been designed for the problem. But questions like whether a better approximation algorithm can be designed, and whether the problem is APX-Hard have been open for quite a while now. In this work we answer the latter question by proving Block Sorting to be Max-SNP-Hard (APX-Hard). The APX-Hardness result is based on a linear reduction of Max-3SAT to Block Sorting. We also provide a new lower bound for the problem via a new parametrized problem k-Block Merging.

  6. HIV, poverty and women.

    Rodrigo, Chaturaka; Rajapakse, Senaka

    2010-03-01

    This review examines the interactions of financial status and HIV and its implications for women. MEDLINE and Google scholar were searched using the keywords 'women', 'poverty' and 'HIV' in any field of the article. The search was limited to articles published in English over the last 10 years. The first section of the article tries to establish whether poverty or wealth is a risk factor for HIV. There is credible evidence for both arguments. While wealth shows an increased risk for both sexes, poverty places women at a special disadvantage. The second section explains how the financial status interacts with other 'non biological' factors to put women at increased risk. While discrimination based on these factors disadvantage women, there are some paradoxical observations that do not fit with the traditional line of explanation (e.g. paradoxical impact of wealth and education on HIV). The final section assesses the impact of HIV in driving poverty and the role of women in interventional programmes. The specific impact of poverty on females in families living with HIV is less explored. Though microfinance initiatives to empower women are a good idea in theory, the actual outcome of such a programme is less convincing. PMID:24037044

  7. Side Effects of HIV Medicines: HIV and Lipodystrophy

    ... of the following HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class . Stavudine (brand name: Zerit) Zidovudine ( ... is an HIV medicine in the non-nucleoside reverse transcriptase inhibitor (NNRTI) drug class . Efavirenz is one of the ...

  8. NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.

    Shahin Ranjbar

    2006-12-01

    Full Text Available To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5, which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.

  9. Frequency and Implications of HIV Superinfection

    Redd, Andrew D.; Quinn, Thomas C; Tobian, Aaron A. R.

    2013-01-01

    HIV superinfection (HIV-SI) occurs when an HIV infected individual is infected with a new distinct HIV viral strain. HIV-SI has been reported throughout the world, and studies have reported HIV-SI incidence rates of 0% to 7.7% per year. Recent use of next-generation sequencing has improved detection of HIV-SI. Several studies have suggested that HIV-SI may occur at rates comparable to initial HIV infection. HIV-SI has been shown to be transmitted by injecting drug use, heterosexual and homose...

  10. Curcumin inhibits HIV-1 by promoting Tat protein degradation

    Ali, Amjad; Banerjea, Akhil C.

    2016-01-01

    HIV-1 Tat is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin independent manner. Curcumin is known to activate 20S proteasome and promotes the degradation of intrinsically unfolded p53 tumor suppressor protein. Since HIV-1 Tat protein is largerly unfolded, we hypothesized that Tat may also be targeted through this pathway. Curcumin treated Tat transfected HEK-293T cells showed a dose and time dependent degradation of Tat protein. Contrary to this HIV-1 Gag which is a properly folded protein, remained unaffected with curcumin. Semi-quantitative RT-PCR analysis showed that curcumin treatment did not affect Tat gene transcription. Curcumin increased the rate of Tat protein degradation as shown by cycloheximide (CHX) chase assay. Degradation of the Tat protein is accomplished through proteasomal pathway as proteasomal inhibitor MG132 blocked Tat degradation. Curcumin also decreased Tat mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. Taken together our study reveals a novel observation that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity. PMID:27283735

  11. Natural antimicrobial peptides as promising anti-HIV candidates

    Wang, Guangshun

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection remains to be one of the major global health problems. It is thus necessary to identify novel therapeutic molecules to combat HIV-1. Natural antimicrobial peptides (AMPs) have been recognized as promising templates for developing topical microbicides. This review systematically discusses over 80 anti-HIV peptides annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Such peptides have been discovered from bacteria, plants, and animals. Examples include gramicidin and bacteriocins from bacteria, cyclotides from plants, melittins and cecropins from insects, piscidins from fish, ascaphins, caerins, dermaseptins, esculentins, and maximins from amphibians, and cathelicidins and defensins from vertebrates. These peptides appear to work by different mechanisms and could block viral entry in multiple ways. As additional advantages, such anti-HIV peptides may possess other desired features such as antibacterial, antiparasital, spermicidal, and anticancer activity. With continued optimization of peptide stability, production, formulation and delivery methods, it is anticipated that some of these compounds may eventually become new anti-HIV drugs. PMID:26834391

  12. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Instructor Guide.

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This instructor guide together with a student guide comprise a set of curriculum materials on the criminal justice system. The instructor guide is a resource for planning and managing individualized, competency-based instruction in six major subject areas or blocks, which are further broken down into several units with some units having several…

  13. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Student Guide.

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This student guide together with an instructor guide comprise a set of curriculum materials on the criminal justice system. The student guide contains self-contained instructional material that students can study at their own pace most of the time. Six major subject areas or blocks, which are further broken down into several units, with some units…

  14. Side Effects of HIV Medicines: HIV and Rash

    Side Effects of HIV Medicines HIV and Rash (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points A rash is an irritated area of ... requires immediate medical attention. Why do people with HIV develop rash? A rash is an irritated area ...

  15. Side Effects of HIV Medicines: HIV and Osteoporosis

    Side Effects of HIV Medicines HIV and Osteoporosis (Last updated 1/11/2016; last reviewed 1/11/2016) Key Points Osteoporosis ... Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Adverse Effects of Antiretroviral Agents From the National Institutes of ...

  16. Identification of dual-tropic HIV-1 using evolved neural networks.

    Fogel, Gary B; Lamers, Susanna L; Liu, Enoch S; Salemi, Marco; McGrath, Michael S

    2015-11-01

    Blocking the binding of the envelope HIV-1 protein to immune cells is a popular concept for development of anti-HIV therapeutics. R5 HIV-1 binds CCR5, X4 HIV-1 binds CXCR4, and dual-tropic HIV-1 can bind either coreceptor for cellular entry. R5 viruses are associated with early infection and over time can evolve to X4 viruses that are associated with immune failure. Dual-tropic HIV-1 is less studied; however, it represents functional antigenic intermediates during the transition of R5 to X4 viruses. Viral tropism is linked partly to the HIV-1 envelope V3 domain, where the amino acid sequence helps dictate the receptor a particular virus will target; however, using V3 sequence information to identify dual-tropic HIV-1 isolates has remained difficult. Our goal in this study was to elucidate features of dual-tropic HIV-1 isolates that assist in the biological understanding of dual-tropism and develop an approach for their detection. Over 1559 HIV-1 subtype B sequences with known tropisms were analyzed. Each sequence was represented by 73 structural, biochemical and regional features. These features were provided to an evolved neural network classifier and evaluated using balanced and unbalanced data sets. The study resolved R5X4 viruses from R5 with an accuracy of 81.8% and from X4 with an accuracy of 78.8%. The approach also identified a set of V3 features (hydrophobicity, structural and polarity) that are associated with tropism transitions. The ability to distinguish R5X4 isolates will improve computational tropism decisions for R5 vs. X4 and assist in HIV-1 research and drug development efforts. PMID:26419858

  17. Research Report: HIV/AIDS

    ... Reports » HIV/AIDS » Letter from the Director HIV/AIDS Email Facebook Twitter Letter from the Director Human ... the virus that causes acquired immune deficiency syndrome (AIDS) — has been with us for three decades now. ...

  18. Women and HIV/AIDS

    ... About Us Contact Us Text size | Print | HIV/AIDS This information in Spanish ( en español ) The human ... HIV, is a sexually transmitted infection and causes acquired immunodeficiency syndrome, or AIDS. Today, about one in four Americans ...

  19. Drugs + HIV, Learn the Link

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

  20. Drugs + HIV, Learn the Link

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

  1. HIV/AIDS in Women

    HIV, the human immunodeficiency virus, kills or damages cells of the body's immune system. The most advanced stage of infection with HIV is AIDS, which stands for acquired immunodeficiency syndrome. ...

  2. HIV/AIDS Clinical Trials

    ... Home Apps APIs Widgets Order Publications Skip Nav HIV/AIDS Clinical Trials Home > Clinical Trials Español small ... Renal (Kidney) Complications/Damage Skin Diseases FDA-Approved HIV Drugs Abacavir Atazanavir Atripla Cobicistat Combivir Complera Darunavir ...

  3. Drugs + HIV, Learn the Link

    Full Text Available ... about the link between drug abuse and HIV. We have produced a set of multicultural public service ... many of us think about HIV/AIDS when we’re at parties or hanging out with friends? ...

  4. Drugs + HIV, Learn the Link

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

  5. Drugs + HIV, Learn the Link

    Full Text Available ... HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the ... risky choices that ultimately led to an HIV-positive diagnosis. The "After the Party" PSA tells the ...

  6. Drugs + HIV, Learn the Link

    Full Text Available ... HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS is a ... time. The virus (HIV) and the disease it causes (AIDS) are often linked and referred to as " ...

  7. 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 ... It provides them with useful information on the science behind drug abuse. NIDA’s Easy-to-Read Drug ...

  8. Drugs + HIV, Learn the Link

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

  9. Drugs + HIV, Learn the Link

    Full Text Available ... to raise awareness among this generation of the real risks of drug use for transmitting HIV, and ... Visual AIDS Bus Boys and Poets Sistahs Getting Real About HIV Conference Radio Stations: WTOP Radio WPFW ...

  10. HIV, AIDS, and Older People

    ... symptoms to appear, or any time in between. Signs of HIV include flu-like symptoms such as headache, cough, diarrhea, fevers, and/or sweats. Additional signs of HIV include swollen glands, lack of energy, loss of ...

  11. Drugs + HIV, Learn the Link

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

  12. HIV/AIDS: Women's Health

    ... 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 ...

  13. What Is HIV/AIDS?

    ... 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 ...

  14. HIV/AIDS and Vaccines

    ... 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. Drugs + HIV, Learn the Link

    Full Text Available ... learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to parents, teachers, and the media about the link between drug abuse and HIV. ...

  16. Drugs + HIV, Learn the Link

    Full Text Available ... function of the human immune system. Loss of these CD4+ cells in people with HIV is a ... HIV/AIDS, and what to do to counter these trends. Online Resources NIDA for Teens Web site : ...

  17. Drugs + HIV, Learn the Link

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

  18. Drugs + HIV, Learn the Link

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

  19. Drugs + HIV, Learn the Link

    Full Text Available ... Post-Award Concerns General Information Grant & Contract Application Process Funding Priorities Research Training News & Events News Nora's ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, National Center for HIV, STD, and ...

  20. Diagnostik af HIV-1 infektionen

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

    1991-01-01

    Different methods have been developed for the diagnosis of HIV infection, i.e. detection of antibodies, antigen and proviral DNA. ELISA methods for detecting HIV-1 antibodies are widely used as screening assays. A sample which is repeatedly positive with ELISA is re-tested with a confirmatory test......, e.g. western blot. Antibodies to HIV-1 are not detectable until 2-3 months after infection, but antigens may be detectable during the last weeks of this initial period, though they disappear with the appearance of the antibodies. In the later stages of HIV infection, HIV antigen is again detectable...... in a proportion of patients. Detection and quantitation of HIV antigen are used as indicators of disease progression and for monitoring the antiviral efficacy of therapeutic interventions. When no antibodies or antigens can be detected in persons suspected of having HIV infection, culture of HIV can...

  1. Drugs + HIV, Learn the Link

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

  2. Pyoderma gangrenosum in HIV patient

    Sayal S

    1997-01-01

    Full Text Available Pyoderma gangrenosum (PG has previously been reported in very few patients with HIV infection. We describe here a 30-year-old housewife with HIV infection having multiple ulcerations over lower limbs characteristic of PG.

  3. Drugs + HIV, Learn the Link

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

  4. Drugs + HIV, Learn the Link

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

  5. Drugs + HIV, Learn the Link

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

  6. Drugs + HIV, Learn the Link

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

  7. Drugs + HIV, Learn the Link

    Full Text Available ... cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/AIDS and Drug Abuse: ... what to do to counter these trends. Online Resources NIDA for Teens Web site : This Web site ...

  8. Drugs + HIV, Learn the Link

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

  9. Drugs + HIV, Learn the Link

    Full Text Available ... Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to cells in the brain and cognitive impairment among methamphetamine abusers than among ...

  10. Creating a National HIV Curriculum.

    Spach, David H; Wood, Brian R; Karpenko, Andrew; Unruh, Kenton T; Kinney, Rebecca G; Roscoe, Clay; Nelson, John

    2016-01-01

    In recent years, the HIV care provider workforce has not kept pace with an expanding HIV epidemic. To effectively address this HIV workforce shortage, a multipronged approach is needed that includes high-quality, easily accessible, up-to-date HIV education for trainees and practicing providers. Toward this objective, the University of Washington, in collaboration with the AIDS Education and Training Center National Coordinating Resource Center, is developing a modular, dynamic curriculum that addresses the entire spectrum of the HIV care continuum. Herein, we outline the general principles, content, organization, and features of this federally funded National HIV Curriculum, which allows for longitudinal, active, self-directed learning, as well as real-time evaluation, tracking, and feedback at the individual and group level. The online curriculum, which is in development, will provide a free, comprehensive, interactive HIV training and resource tool that can support national efforts to expand and strengthen the United States HIV clinical care workforce. PMID:27086188

  11. Drugs + HIV, Learn the Link

    Full Text Available ... blood cell that is crucial to the normal function of the human immune system. Loss of these ... of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to ...

  12. ORAL CANDIDIASIS AND HIV INFECTION

    Prabhu, Rachana Vishnudas

    2013-01-01

    The acquired immunodeficiency syndrome (AIDS) pandemic, caused by infection with human immunodeficiency virus (HIV) dramatically illustrates the awesome transmission capabilities of disease. Oral manifestations of HIV have been important in identification of patients harboring the HIV virus and in predicting the decline in their immune system Oral candidiasis is one of the earliest premonitory signs of HIV infection and its diagnosis may have grave prognostic implications for the eventual dev...

  13. Living with HIV: Patients Perspective

    2009-06-04

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

  14. Drugs + HIV, Learn the Link

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

  15. Drugs + HIV, Learn the Link

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

  16. Drugs + HIV, Learn the Link

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

  17. 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 ... at: https://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  18. Drugs + HIV, Learn the Link

    Full Text Available ... Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to ... shown to increase the amount of HIV in brain cells 1 . Drug abuse treatment. Since the late 1980s, research has shown that treating drug abuse is an ...

  19. Drugs + HIV, Learn the Link

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

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

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

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

  1. Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial

    Jairam R Lingappa; Lambdin, Barrot; Bukusi, Elizabeth Ann; Ngure, Kenneth; Kavuma, Linda; Inambao, Mubiana; Kanweka, William; Allen, Susan; Kiarie, James N.; Were, Edwin; Manongi, Rachel; Coetzee, David; de Bruyn, Guy; Delany-Moretlwe, Sinead; MAGARET, Amalia

    2008-01-01

    Background: Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 preval...

  2. Left bundle-branch block

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

    2013-01-01

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

  3. Learning Potentials in Number Blocks

    Majgaard, Gunver; Misfeldt, Morten; Nielsen, Jacob

    2012-01-01

    This paper describes an initial exploration of how an interactive cubic user-configurable modular robotic system can be used to support learning about numbers and how they are pronounced. The development is done in collaboration with a class of 7-8 year old children and their mathematics teacher....... The tool is called Number Blocks and it combines physical interaction, learning, and immediate feedback. Number Blocks supports the children's understanding of place value in the sense that it allows them to experiment with creating large numbers. We found the blocks contributed to the learning...... process in several ways. The blocks combined mathematics and play, and they included and supported children at different academic levels. The auditory representation, especially the enhanced rhythmic effects due to using speech synthesis, and the rhythm helped the children to pronounce large numbers. This...

  4. Linear characters and block algebra

    Zeng, Jiwen

    2011-01-01

    This paper will prove that: 1. $G$ has a block only having linear ordinary characters if and only if $G$ is a $p$-nilpotent group with an abelian Sylow $p$-subgroup; 2. $G$ has a block only having linear Brauer characters if and only if $O_{p'}(G)\\leq O_{p'p}(G)=HO_{p'}(G)= \\textrm{Ker}(B_{0}^{*}) \\leq O_{p'pp'}=G$, where $H=G^{'}O^{p'}(G), \\textrm{Ker}(B_{0}^{*})=\\bigcap_{\\lambda \\in \\textrm{IBr}(B_{0})} \\textrm{Ker}(V_{\\lambda}), B_{0}$ is the principal block of $G$ and $V_{\\lambda}$ is the $F[G]$-module affording the Brauer character $\\lambda$; 3. if $G$ satisfies the conditions above, then for any block algebra $B$ of $G$, we have

  5. Recursion Relations for Conformal Blocks

    Penedones, João; Yamazaki, Masahito

    2015-01-01

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

  6. The wild tapered block bootstrap

    Hounyo, Ulrich

    In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block......-of-the-art block-based method in terms of asymptotic accuracy of variance estimation and distribution approximation. For stationary time series, the asymptotic validity, and the favorable bias properties of the new bootstrap method are shown in two important cases: smooth functions of means, and M-estimators. The...... estimator for the sample mean is shown to be robust against heteroskedasticity of the wild tapered block bootstrap. This easy to implement alternative bootstrap method works very well even for moderate sample sizes....

  7. MarineMineralsProgramBlocks

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

  8. HIV in Southeast Asia.

    Abrams, S

    1998-01-01

    This article explores the HIV/AIDS epidemic in Southeast Asia. Prostitution and injecting drug use are two major factors in the appearance of HIV/AIDS in a country. But, it is the correct social network that assures its transmission to epidemic proportions. Heterosexual transmission in Cambodia, Myanmar, and Thailand is linked with prevalence among female sex workers and their clients. In Malaysia, the Ministry of Health responded immediately, but the number of new infections continued to increase. The failures suggest the need for more effective, intensive health education programs, outreach by nongovernmental organizations, and peer education at the grassroots level and in remote areas. Public health officials need to promote political change. International agencies could play an important role, if countries such as Myanmar, Cambodia, and Viet Nam were open to international exchanges. In Myanmar, political unrest has a priority over the need for aggressive health interventions. In Indonesia, the Islamic influence prevents recognition of the country's significant sex industry or the existence of a homosexual community. In Cambodia, health officials warned about the high number of sexual partners, high mobility rate, and low condom use, but HIV spread rapidly in the 1990s. Thailand initiated a 100% condom campaign to combat HIV prevalence in the 1990s, and HIV prevalence declined among sex workers and military recruits. Risk factors for rapid transmission include mobility, the number of sexual partners/sex worker, the proportion engaging in commercial sex, and the rate of regular condom use among sex workers. PMID:12294443

  9. HIV Sequence Compendium 2015

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

    2015-10-05

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

  10. Statistical cryptanalysis of block ciphers

    Junod, Pascal

    2005-01-01

    Since the development of cryptology in the industrial and academic worlds in the seventies, public knowledge and expertise have grown in a tremendous way, notably because of the increasing, nowadays almost ubiquitous, presence of electronic communication means in our lives. Block ciphers are inevitable building blocks of the security of various electronic systems. Recently, many advances have been published in the field of public-key cryptography, being in the understanding of involved securi...

  11. A Novel Tetrathiafulvalene Building Block

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

    1999-01-01

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

  12. Risking Aggression: Reply to Block

    Kris Borer

    2010-05-01

    Full Text Available In his paper, “Is There an ‘Anomalous’ Section of the Laffer Curve?”, Walter Block describes some situations in which it appears that a libertarian should violate the non-aggression principle. To rectify this, Block proposes a different perspective on libertarianism which he calls punishment theory. This paper argues that no new theory is needed, as the non-aggression principle can be used to resolve theapparent conundrums.

  13. Risking Aggression: Reply to Block

    Kris Borer

    2010-01-01

    In his paper, “Is There an ‘Anomalous’ Section of the Laffer Curve?”, Walter Block describes some situations in which it appears that a libertarian should violate the non-aggression principle. To rectify this, Block proposes a different perspective on libertarianism which he calls punishment theory. This paper argues that no new theory is needed, as the non-aggression principle can be used to resolve theapparent conundrums.

  14. Statistical cryptanalysis of block ciphers

    Junod, Pascal; Vaudenay, Serge

    2007-01-01

    Since the development of cryptology in the industrial and academic worlds in the seventies, public knowledge and expertise have grown in a tremendous way, notably because of the increasing, nowadays almost ubiquitous, presence of electronic communication means in our lives. Block ciphers are inevitable building blocks of the security of various electronic systems. Recently, many advances have been published in the field of public-key cryptography, being in the understanding of involved securi...

  15. Techniques of facial nerve block.

    Schimek, F; Fahle, M

    1995-01-01

    The efficacy of different techniques of facial nerve block for cataract surgery was investigated. Forty four patients underwent either modified O'Brien, Atkinson, van Lint, or lid blocks. Intentional muscle activity of the orbicularis oculi muscle was recorded and the area under the EMG curve calculated for quantitative comparison of muscle activity between the groups before and after injection of lignocaine with the vasoconstrictor naphazoline nitrate. In addition, the force of lid closure w...

  16. NANOSTRUCTURES OF FUNCTIONAL BLOCK COPOLYMERS

    Guojun Liu

    2000-01-01

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

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

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

    1997-01-01

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

  18. Changes in HIV knowledge, and socio-cultural and sexual attitudes in South India from 2003-2009

    Bradley Janet; Rajaram S; Moses Stephen; Bhattacharjee Parinita; Lobo Anil M; Ramesh BM; Washington Reynold; Alary Michel

    2011-01-01

    Abstract Background As communities face serious pressures on traditional values, such as those posed by HIV infection, cultural inertia may result, whereby existing trends towards more liberalized views of sexuality are stalled. We examined changes in attitudes around HIV in Bagalkot district, south India, between 2003 and 2009. Methods General population surveys were conducted in 2003 and 2009, among approximately 6,600 randomly sampled men and women in 10 villages and 20 urban blocks of Bag...

  19. Laboratory diagnostics for HIV infection

    Stefano Buttò

    2010-03-01

    Full Text Available Laboratory diagnosis of human immunodeficiency virus (HIV infection is fundamental for detecting and monitoring infection. Many diagnostic tools are available that are based on both detection of HIV-specific antibodies and virus antigen, or nucleic acid. As technology evolves, HIV testing assays are being improved providing better sensitivity and specificity. In this short review, we summarize the common and new methodologies that are being used in laboratories, from the HIV antibody-based assays to the new tests for the detection of HIV nucleic acids.

  20. Methamphetamine activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces human immunodeficiency virus (HIV) transcription in human microglial cells

    Wires, Emily S.; Alvarez, David; Dobrowolski, Curtis; Wang, Yun; Morales, Marisela; Karn, Jonathan; Harvey, Brandon K.

    2012-01-01

    Human immunodeficiency virus (HIV) primarily infects glial cells in the central nervous system (CNS). Recent evidence suggests that HIV-infected individuals who abuse drugs such as methamphetamine (METH) have higher viral loads and experience more severe neurological complications than HIV-infected individuals who do not abuse drugs. The aim of this study was to determine the effect of METH on HIV expression from the HIV long terminal repeats (LTR) promoter and on an HIV integrated provirus in microglial cells, the primary host cells for HIV in the CNS. Primary human microglial cells immortalized with SV40 T-antigen (CHME-5 cells) were co-transfected with an HIV LTR reporter and the HIV Tat gene, a key regulator of viral replication and gene expression, and exposed to METH. Our results demonstrate that METH treatment induced LTR activation, an effect potentiated in the presence of Tat. We also found that METH increased the nuclear translocation of the nuclear factor kappa B (NF-κB), a key cellular transcriptional regulator of the LTR promoter, and the activity of an NF-κB-specific reporter plasmid in CHME-5 cells. The presence of a dominant-negative regulator of NF-κB blocked METH-related activation of the HIV LTR. Furthermore, treatment of HIV-latently infected CHME-5 (CHME-5/HIV) cells with METH induced HIV expression in a dose-dependent manner, and nuclear translocation of the p65 subunit of NF-κB. These results suggest that METH can stimulate HIV gene expression in microglia cells through activation of the NF-κB signaling pathway. This mechanism may outline the initial biochemical events leading to the observed increased neurodegeneration in HIV-positive individuals who use METH. PMID:22618514

  1. 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

    2012-02-01

    Rhesus TRIM5α (TRIM5α(rh)) is a cytosolic protein that potently restricts HIV-1 at an early postentry stage, prior to reverse transcription. The ability of TRIM5α(rh) 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 TRIM5α(rh) RING domain mutants that potently restrict HIV-1 but allow the occurrence of reverse transcription. These TRIM5α(rh) RING variants blocked HIV-1 infection after reverse transcription but prior to integration, as suggested by the routing of nuclear viral DNA to circularization in the form of 2-long terminal repeat (2-LTR) circles. The folding of RING domain variants was similar to that of the wild type, as evaluated by nuclear magnetic resonance. RING domain changes that allowed the occurrence of reverse transcription were impaired in their ability to decrease the amount of pelletable capsid compared with wild-type TRIM5α. Similar effects of this particular group of mutations were observed with human TRIM5α inhibition of N-tropic murine leukemia virus (N-MLV). Interestingly, TRIM5α(rh) RING domain variants also prevented the degradation of TRIM5α(rh) that occurs following cell entry of HIV-1. These data correlated the block of reverse transcription with the ability of TRIM5α to accelerate uncoating. Collectively, these results suggest that TRIM5α(rh) blocks HIV-1 reverse transcription by inducing premature viral uncoating in target cells. PMID:22114335

  2. Preventing HIV infection.

    Coates, T J; Collins, C

    1998-07-01

    The primary way of preventing HIV infections is to change behaviors that enable transmission of the virus, specifically those behaviors relating to sex and drug injection. Realistic public health workers have focused on encouraging adoption of safer sexual practices, primarily condom use. The fundamental way to persuade people to engage in preventive practices is through targeted education aimed at particularly at-risk communities. Other effective behavioral interventions against HIV infections are: testing and follow-up counseling; comprehensive sex education; peer influence and community action; advertising and marketing; easing access to condoms; physician-patient dialogue; drug treatment; access to clean needles; and direct outreach. On the contrary, interventions that do not work are the following: one-time exposure to information; delivering a single message; abstinence-only programs; and coercive measures to identify people with HIV or their sexual partners. PMID:9648304

  3. [Study of gonadal hormone drugs in blocking filovirus entry of cells in vitro].

    Wang, Li-li; Chen, Qing; Zhou, Li-na; Guo, Ying

    2015-12-01

    This study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. One thousand and six hundred drugs were screened using the ZEBOV-GP/HIV model, a pseudovirus formed by an HIV-core packed with the Zaire Ebola virus glycoprotein. We identified 12 gonadal hormone drugs with inhibitory activities in ZEBOV-GP/HIV entry at final concentration of 10 μmol x L(-1). Among them, three drugs exhibited strong activities with IC50 raloxifene hydrochloride (IC50: 3.48 ± 0.07 μmol x L(-1)), equilin (IC50: 4.00 ± 9.94 μmol x L(-1)), estradiol (IC50: 5.26 ± 9.92 μmol x L(-1)), quinestrol (IC50: 6.36?5.37 gmol-L1), estrone (IC50: 6.87 ± 0.03 μmol-L1) and finasteride (IC50: 9.94 ± 0.45 μmol x L(-1)); two drugs, hexestrol (IC50: 14.20 ± 0.55 μmol x L(-1)) and chlormadinone acetate (IC50: 24.60 ± 0.36 μmol x L(-1)), had weak activities against ZEBOV. Further, toremifene citrate, tamoxifen citrate, clomiphene citrate, raloxifene hydrochloride and quinestrol could block both pseudovirus type Sudan ebola virus (SEBOV-GP/HIV) and Marburg virus (MARV-GP/HIV) entries. PMID:27169275

  4. Revisiting HIV-1 uncoating

    Arhel Nathalie

    2010-11-01

    Full Text Available 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 with difficulties, particularly as a result of the vulnerability of the capsid assembly to experimental manipulation. Nevertheless, recent studies of capsid structure, retroviral restriction and mechanisms of nuclear import, as well as the recent expansion of technical advances in genome-wide studies and cell imagery approaches, have substantially changed our understanding of HIV uncoating. Although early work suggested that uncoating occurs immediately following viral entry in the cell, thus attributing a trivial role for the capsid in infected cells, recent data suggest that uncoating occurs several hours later and that capsid has an all-important role in the cell that it infects: for transport towards the nucleus, reverse transcription and nuclear import. Knowing that uncoating occurs at a later stage suggests that the viral capsid interacts extensively with the cytoskeleton and other cytoplasmic components during its transport to the nucleus, which leads to a considerable reassessment of our efforts to identify potential therapeutic targets for HIV therapy. This review discusses our current understanding of HIV uncoating, the functional interplay between infectivity and timely uncoating, as well as exposing the appropriate methods to study uncoating and addressing the many questions that remain unanswered.

  5. Revisiting HIV-1 uncoating.

    Arhel, Nathalie

    2010-01-01

    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 with difficulties, particularly as a result of the vulnerability of the capsid assembly to experimental manipulation. Nevertheless, recent studies of capsid structure, retroviral restriction and mechanisms of nuclear import, as well as the recent expansion of technical advances in genome-wide studies and cell imagery approaches, have substantially changed our understanding of HIV uncoating. Although early work suggested that uncoating occurs immediately following viral entry in the cell, thus attributing a trivial role for the capsid in infected cells, recent data suggest that uncoating occurs several hours later and that capsid has an all-important role in the cell that it infects: for transport towards the nucleus, reverse transcription and nuclear import. Knowing that uncoating occurs at a later stage suggests that the viral capsid interacts extensively with the cytoskeleton and other cytoplasmic components during its transport to the nucleus, which leads to a considerable reassessment of our efforts to identify potential therapeutic targets for HIV therapy. This review discusses our current understanding of HIV uncoating, the functional interplay between infectivity and timely uncoating, as well as exposing the appropriate methods to study uncoating and addressing the many questions that remain unanswered. PMID:21083892

  6. HIV/AIDS Clinical Trials Fact Sheet

    HIV Prevention HIV/AIDS Clinical Trials (Last updated 9/15/2015; last reviewed 9/15/2015) Key Points HIV/AIDS clinical ... safe and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help ...

  7. Aggressive HIV-1?

    van der Hoek Lia; de Ronde Anthony; Berkhout Ben

    2005-01-01

    Abstract New York City health officials announced on February 11, 2005 that a patient rapidly developed full-blown AIDS shortly after being diagnosed with a rare, drug-resistant strain of HIV-1. The New York City Department of Health issued an alert to all hospitals and doctors and a press conference was held to announce the emergence of an aggressive HIV-1 strain that may be difficult to treat and that appears to trigger rapid progression to AIDS. Is the panic justified?

  8. Benchmarking HIV health care

    Podlekareva, Daria; Reekie, Joanne; Mocroft, Amanda;

    2012-01-01

    ABSTRACT: BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV-patients based on four key indicators. METHODS: Four indicators of health care were...... to North, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for East and Argentina (adjusted OR 0.16[95%CI 0.11-0.23, p care utilization...

  9. Leishmaniasis in HIV infection.

    Paredes R

    2003-01-01

    Full Text Available Herein we review the particular aspects of leishmaniasis associated with HIV infection. The data in this review are mainly from papers identified from PubMed searches and from papers in reference lists of reviewed articles and from the authors′ personal archives. Epidemiological data of HIV/Leishmania co-infection is discussed, with special focus on the influence of Highly Active Antiretroviral Therapy (HAART on incidence of leishmaniasis and transmission modalities. Microbiological characteristics, pathogenesis, clinical presentation and specific treatment of the co-infection are also presented.

  10. Crystal structures of HIV-1 nonnucleoside reverse transcriptase inhibitors: N-benzyl-4-methyl-benzimidazoles

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-07-01

    HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase.

  11. PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads.

    Edward Seung

    Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

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

    Barré-Sinoussi Françoise

    2009-05-01

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

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

    Tomlinson Stephen

    2010-06-01

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

  14. Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B expressing four HIV-1 antigens and potentiation by specific gene deletions.

    Juan García-Arriaza

    Full Text Available BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B, that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R, known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R. A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+ and CD8(+ T cells, with the CD8(+ T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+ and CD8(+ T-cell immune responses. HIV-1-specific CD4(+ T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+ T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+ T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R

  15. HIV peripheral neuropathy.

    Gabbai, Alberto Alain; Castelo, Adauto; Oliveira, Acary Souza Bulle

    2013-01-01

    Peripheral neuropathies are the most common neurological manifestations occurring in HIV-infected individuals. Distal symmetrical sensory neuropathy is the most common form encountered today and is one of the few that are specific to HIV infection or its treatment. The wide variety of other neuropathies is akin to the neuropathies seen in the general population and should be managed accordingly. In the pre-ART era, neuropathies were categorized according to the CD4 count and HIV viral load. In the early stages of HIV infection when CD4 count is high, the inflammatory demyelinating neuropathies predominate and in the late stages with the decline of CD4 count opportunistic infection-related neuropathies prevail. That scenario has changed with the present almost universal use of ART (antiretroviral therapy). Hence, HIV-associated peripheral neuropathies are better classified according to their clinical presentations: distal symmetrical polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuropathies, mononeuropathies multiplex and cranial neuropathies, autonomic neuropathy, lumbosacral polyradiculomyelopathy, and amyotrophic lateral sclerosis (ALS)-like motor neuropathy. Treated with ART, HIV-infected individuals are living longer and are at a higher risk of metabolic and age-related complications; moreover they are also prone to the potentially neurotoxic effects of ART. There are no epidemiological data regarding the incidence and prevalence of the peripheral neuropathies. In the pre-ART era, most data were from case reports, series of patients, and pooled autopsy data. At that time the histopathological evidence of neuropathies in autopsy series was almost 100%. In large prospective cohorts presently being evaluated, it has been found that 57% of HIV-infected individuals have distal symmetrical sensory neuropathy and 38% have neuropathic pain. It is now clear that

  16. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767stop, which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752N750K) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  17. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. PMID:24859335

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

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

    2015-08-01

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

  19. In vitro anti-HIV-1 activities of resveratrol derivatives%白藜芦醇衍生物体外抗HIV-1活性的初步研究

    黄宁; 杨柳萌; 王睿睿; 朱海亮; 郑永唐

    2012-01-01

    Objective; To study the in vitro anti-HIV-1 activities of resveratrol derivatives and the mechanisms. Methods; The cytotoxicities of compounds were tested by MTT assay. The anti-HIV activities of compounds in acute infection were evaluated by cytopathogenic effect (CPE) assay. The inhibition of HIV-lKm018 replication in PBMC was evaluated by p24 antigen expression. The fusion between of HIV-1 infected and uninfected cells was e-valuated by CPE. The inhibition of HIV-1 recombinant reverse transcriptase activity, HIV-1 recombinant protease activity and direct HIV-1 virus killing were used to determine the mechanism. Results; IFB-1 and IFB-9 from resveratrol derivatives markedly inhibited syncytium formation with selective indexes of 16. 16 and 230.27 , respectively. IFB-1 and IFB-9 suppressed HIV-1 p24 antigen production in acutely HIV-111IB-infected C8166 cells with EC50, of 14.57 and 0.23 μg·mL-1 , respectively. They also inhibited HIV-lKM018 replication in PBMC. IFB-1 and IFB-9 blocked the fusion between normal cells and chronically HIV-1-infected cells, but did not inhibit recombinant RT, PR activities and did not directly kill HIV-1. Conclusions; IFB-1 and IFB-9 show potential anti-HIV-1 activities and the mechanism might be associated with inhibition virus entry.%目的:检测白藜芦醇衍生物IFB-1和IFB-9的体外抗HIV-1活性,并对其进行抗HIV-1作用机制的初步研究.方法:采用MTT比色法检测白藜芦醇衍生物IFB-1和IFB-9的细胞毒性;细胞病变法检测化合物对HIV-1急性感染的抑制活性;采用HIV-1 p24抗原ELISA方法检测临床分离株HIV-1KM018在PBMC中复制的抑制实验;采用细胞病变法检测HIV-1感染和未感染细胞之间的融合;采用HIV-1重组逆转录酶活性抑制实验,HIV-1重组蛋白酶活性抑制实验以及直接杀病毒实验来研究化合物体外抗HIV-1机制.结果:白藜芦醇衍生物IFB-1和IFB-9对HIV-1 ⅢB诱导的合胞体形成抑制的选择指数分别为16

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

    Dobson Wendy

    2011-06-01

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

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

    Felipe Diaz-Griffero

    2011-04-01

    Full Text Available 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, around the endocytic vesicle, evidence for the ability of TRIM5α to assemble a similar type of structure surrounding the HIV-1 core has been lacking. Recent work by Ganser-Pornillos, Chandrasekaran and colleagues has now demonstrated the ability of the restriction factor TRIM5α to “cage” or “net” the HIV-1 core by forming an hexagonal array on the surface of the viral capsid [1]. This hexagonal array is strikingly similar in design to the array formed by the clathrin triskelion on the surface of the clathrin-coated endocytic vesicle. This remarkable finding represents an important advance on our understanding of the restriction factor TRIM5α, and suggests that TRIM5α cages the HIV-1 core in order to terminate infection. The present note discusses the implications of this discovery.

  2. Caging the beast: TRIM5α binding to the HIV-1 core.

    Diaz-Griffero, Felipe

    2011-05-01

    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, around the endocytic vesicle, evidence for the ability of TRIM5α to assemble a similar type of structure surrounding the HIV-1 core has been lacking. Recent work by Ganser-Pornillos, Chandrasekaran and colleagues has now demonstrated the ability of the restriction factor TRIM5α to "cage" or "net" the HIV-1 core by forming an hexagonal array on the surface of the viral capsid. This hexagonal array is strikingly similar in design to the array formed by the clathrin triskelion on the surface of the clathrin-coated endocytic vesicle. This remarkable finding represents an important advance on our understanding of the restriction factor TRIM5α, and suggests that TRIM5α cages the HIV-1 core in order to terminate infection. The present note discusses the implications of this discovery. PMID:21994740

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

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

    2016-01-01

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

  4. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  5. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide.

    Ravot, E; Lisziewicz, J; Lori, F

    1999-12-01

    The tenacious effort to develop new, specific agents to treat HIV infection is currently accompanied by a reconsideration of existing drugs on the basis of their known or putative effects on the retroviral life cycle and/or the tuning of immune mechanisms. Three specific 'older' compounds that interfere with HIV infection by both a direct antiviral activity, and a modulation of T-cell activation and proliferation have received the most attention. Hydroxurea, a classical chemotherapeutic agent, inhibits retroviral reverse transcription by targeting a cellular enzyme responsible for the synthesis of deoxynucleoside triphosphates. It may also have a role in reducing viral load while maintaining low numbers of potential target T cells. Beneficial effects of hydroxyurea in combination with didanosine and/or stavudine on viral load have been shown in a number of clinical trials. Cyclosporin, a known immunosuppressant, blocks the activation of T cells, hence reducing the permissivity to HIV, and also prevents proper HIV virion maturation. However, clinical studies have produced conflicting results in HIV-infected patients with regard to immunological and disease effects and toxicity. Thalidomide may have antiretroviral effects as a result of its primarily inhibitory effects on the production of tumour necrosis factor alpha (TNFalpha). TNFalpha induces expression of HIV from chronically infected cell lines by stimulating a cellular transcription factor, and blocking of TNFalpha-stimulated HIV replication by thalidomide has been shown in vitro and ex vivo. However, the effects on TNFalpha production in vivo have been inconsistent. Thalidomide has shown potential in treating some AIDS-related conditions [cachexia (weight loss and muscle wasting), and aphtous oral, oesophageal or genital ulcers]. However, because of its numerous and major adverse effects, thalidomide should always be used cautiously. In summary, some older drugs have potential as anti-HIV agents and offer the

  6. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells.

    Kara G Lassen

    2006-07-01

    Full Text Available HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART. We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications.

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

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

    1997-01-01

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

  8. Projectors, Shadows, and Conformal Blocks

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the "shadow formalism" of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the "embedding space" R^{d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  9. Climatological features of blocking anticyclones

    Several climatological studies have been previously performed using large observational data sets (i.e., 10 years or longer) in order to determine the predominant characteristics of blocking anticyclones, including favored development regions, duration, preferred seasonal occurrence, and frequency of occurrence. These studies have shown that blocking anticyclones occur most frequently from October to April over the eastern Atlantic and Pacific oceans downstream from both the North American and Asian continental regions and the storm track regions to the east of these continents. Some studies have also revealed the presence of a third region block formation in western Russia near 40 degrees E which is associated with another storm track region over the Mediterranean and western Asia

  10. Tharsis block tectonics on Mars

    Raitala, Jouko T.

    1988-01-01

    The concept of block tectonics provides a framework for understanding many aspects of Tharsis and adjoining structures. This Tharsis block tectonics on Mars is manifested partly by mantle-related doming and partly by response to loading by subsequent volcanic construction. Although the origin of the volcanism from beneath Tharsis is a subject of controversy explanations have to include inhomogeneities in Martian internal structure, energy distribution, magma accumulation and motion below the lithosphere. Thermal convection can be seen as a necessary consequence for transient initial phase of Martian cooling. This produced part of the elevated topography with tensional stresses and graben systems radial to the main bulge. The linear grabens, radial to the Tharsis center, can be interpreted to indicate rift zones that define the crustal block boundaries. The load-induced stresses may then have contributed on further graben and ridge formation over an extended period of time.

  11. HIV Excess Cancers JNCI

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

  12. Modeling HIV Cure

    Perelson, Alan; Conway, Jessica; Cao, Youfang

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

  13. Psychotropic Drugs and HIV

    Ana-Lúcia Moreira

    2014-06-01

    Full Text Available Background: HIV/AIDS infection is frequently associated with psychiatric disor- ders like psychosis, depression and anxiety. Psychiatric comorbidities may interfere with adherence to antiretroviral treatment. Therefore, diagnosis and treatment of these conditions are essential. However, the administration of a psychotropic drug to HAART therapy can result in drug interactions.Objectives: This review aims to analyze the various psychotropic drugs that can be used in these patients, as well as the interactions and adverse reactions that may occur. Methods: A MEDLINE search on anglo-saxonic literature was conducted, from 1993 until 2011, using the key-words: HIV, AIDS, psychosis, depression, anxiety, secondary mania, antidepressive agents, antipsychotics, benzodiazepines, HAART. Results: We found 100 articles, of which 66 were included and 34 excluded. The articles that showed no specific data on the use of psychotropic drugs in HIV patients were excluded. Discussion: Pharmachologic interactions may occur by occupation of the same metabolic pathways. Further research is needed with indications for best practices. Psychotherapeutic interventions should be considered. Conclusion: The choice of the therapeutic intervention, namely when considering psychotropic drugs with the lowest number of interactions and adverse effects is crucial in order to achieve therapeutic success in the treatment of HIV infected patients.

  14. HIV and Pulmonary Hypertension

    ... HIV AIDS.gov: www.aids.gov AIDS Healthcare Foundation: www.hivcare.org POZ Magazine: www.poz.com • Educational conferences and materials for medical professionals and patients • A wealth of information in the Survival Guide • PH patient ...

  15. HIV and development.

    Decosas, J

    1996-12-01

    Global patterns of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) are consistent with indicators of social development. The highest HIV prevalence is found in poor societies, societies in turmoil, and among the displaced, powerless, and marginalized. AIDS is an indicator of uneven or dysfunctional development, a cause of developmental delays, and a result of inadequacies in the development of health and social services. Factors such as untreated sexually transmitted diseases, the education of women and their level of autonomy to seek medical care, the availability and quality of medical services, large age differences between men and women in sexual partnerships, prostitution as a means of economic survival, and labor migration and refugee movements play key roles in the generation of AIDS epidemics. The impact of HIV on the feminization of poverty and the maldistribution of household wealth is one of the most significant developmental effects. In areas with high HIV prevalence, crop yields and soil fertility are declining, pests and plant diseases are spreading, and starchy crops of low nutritional value are replacing more labor-intensive traditional crops. Finally, AIDS exerts a major impact on the human development index, especially life expectancy at birth. PMID:8970714

  16. Block ground interaction of rockfalls

    Volkwein, Axel; Gerber, Werner; Kummer, Peter

    2016-04-01

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

  17. HIV/AIDS and the Flu

    ... this? Submit What's this? Submit Button Past Newsletters HIV/AIDS and the Flu Questions & Answers Language: English ... to people with HIV/AIDS. Should people with HIV/AIDS receive the inactivated influenza vaccine? People with ...

  18. Managing Your Treatment of HIV/AIDS

    ... HIV/AIDS This information in Spanish ( en español ) Managing your treatment of HIV/AIDS Related information How ... any reason. Return to top More information on Managing your treatment of HIV/AIDS Explore other publications ...

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

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

  20. OPAL 96 Blocks Lead Glass

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

  1. Cryptanalysis of Selected Block Ciphers

    Alkhzaimi, Hoda A.

    architectures and frameworks. For a long time they were known as the main building block that will provide confidentiality in an information system. They would also be able to represent a full spectrum of cryptographic services as many block ciphers can be used to construct stream ciphers, hash functions...... PRINTcipher for a significant fraction of its keys. This new attack also gives us new insights into other, more well-established attacks. In addition, we also show that for weak keys, strongly biased linear approximations exists for any number of rounds. Furthermore, we provide variety of attacks...

  2. Infant feeding and HIV

    Ameena Ebrahim Goga

    2009-12-01

    Full Text Available Recent studies on antiretroviral prophylaxis during breastfeeding show that maternal HAART (alone or with 1,4 or 24 weeks infant prophylaxis or infant prophylaxis alone (with limited maternal prophylaxis for 6, 14 or 24 weeks reduces HIV transmission through breastmilk (postnatal transmission. Maternal postnatal regimens appear to be as efficacious as infant postnatal regimens, although one study shows a trend favouring infant nevirapine over maternal HAART (both used from 1 week to 6 months post-delivery. These new findings necessitate a review of existing PMTCT interventions, and the immediate implementation of regimens that reduce postnatal transmission - where this is feasible – to save children’s lives. In the public sector, whilst stakeholders engage in discussions about which is the best regimen to minimise postnatal transmission SSSUPPORT should be given to all HIV-positive women, as explained below, to improve infant outcomes and reduce postnatal transmission: Screen all women for HIV, Send off CD4 cell counts on all HIV-positive women, Screen all HIV-positive women for AFASS using a standardised tool (e.g. Table 3; Understand the woman’s personal and socio-cultural context; Promote exclusive or predominant breastfeeding if all AFASS criteria are not met; Promote exclusive formula feeding if all AFASS criteria are met; Organise supplies of formula milk and cotrimoxazole; Review mothers and infants in the first 3 days post-delivery, in the first two weeks postnatally and monthly thereafter, and review health and feeding practices, regardless of feeding choice, at every visit; lastly Treat all pregnant women with HAART if they meet national criteria for HAART initiation.

  3. HIV Sequence Compendium 2010

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

    2010-12-31

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

  4. A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains

    Lu Lu

    2012-12-01

    Full Text Available Abstract Background Most currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4 can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell. Results We engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI, but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT. Conclusion This bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.

  5. Morphine Enhances HIV Infection of Neonatal Macrophages

    Li, Yuan; MERRILL, JEFFREY D.; Mooney, Kathy; Song, Li; Wang, Xu; GUO, CHANG-JIANG; Savani, Rashmin C; Metzger, David S.; Douglas, Steven D.; Ho, Wen-Zhe

    2003-01-01

    Perinatal transmission of HIV accounts for almost all new HIV infections in children. There is an increased risk of perinatal transmission of HIV with maternal illicit substance abuse. Little is known about neonatal immune system alteration and subsequent susceptibility to HIV infection after morphine exposure. We investigated the effects of morphine on HIV infection of neonatal monocyte-derived macrophages (MDM). Morphine significantly enhanced HIV infection of neonatal MDM. Morphine-induced...

  6. Role of HIV in Amyloid Metabolism

    Ortega, Mario; Ances, Beau M.

    2014-01-01

    HIV infection has changed from an acute devastating disease to a more chronic illness due to combination anti-retroviral treatment (cART). In the cART era, the life expectancy of HIV-infected (HIV+) individuals has increased. More HIV+ individuals are aging with current projections suggesting that 50% of HIV+ individuals will be over 50 years old by 2015. With advancing age, HIV+ individuals may be at increased risk of developing other potential neurodegenerative disorders [especially Alzheim...

  7. Developing strategies for HIV-1 eradication

    Durand, Christine M.; Blankson, Joel N.; Siliciano, Robert F.

    2012-01-01

    Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication, transforming the outlook for infected patients. However, reservoirs of replication-competent forms of the virus persist during HAART, and when treatment is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1 latency, as well as a report that HIV-1 infection was eradicated in one individual, have renewed interest in finding a cure for HIV-1 infection. Strategies for HIV-1 eradication include gene...

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

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

    2016-01-01

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

  9. In vitro anti-HIV-1 activities of Qishile, a Chinese medicine effective fraction formula%中药有效部位复方奇士乐体外抗HIV-1活性研究

    杨柳萌; 王睿睿; 张高红; 张兴杰; 陈纪军; 郑永唐

    2011-01-01

    目的 评价有效部位复方奇士乐(QSL)的体外抗HIV-1药效学.方法 通过合胞体抑制、HIV-1感染细胞保护、HIV-1 p24抗原测定等方法检测急性感染中QSL对HIV-1实验株、临床分离株、耐药株的抑制作用和对慢性感染细胞中病毒复制的影响;通过ELISA方法和荧光法分别检测了QSL体外抑制HIV-1逆转录酶和蛋白酶活性作用.结果 有效部位复方制剂QSL能有效地抑制HIV-1ⅢB诱导淋巴细胞病变、保护HIV-1ⅢB感染MT-4细胞死亡、阻断HIV-1ⅢB慢性感染H9细胞与C8166细胞间融合的作用.QSL对HIV-1实验株HIV-1ⅢB、临床分离株HIV-1KM018、耐药株HIV-174V的病毒复制也有较好的抑制作用.QSL抑制HIV活性的作用机制可能为多靶点,主要是抑制HIV逆转录酶、蛋白酶和病毒进入细胞.结论 QSL是具有较好体外抗HIV-1活性的中药有效部位复方.%Aim To evaluate the anti-HIV-1 activities of Qishile ( QSL) in vitro , a Chinese medicine effective fraction formula. Methods The inhibition of syncytia formation induced by HIV -1 was determined under microscopy. The protection of HIV-1 induced MT-4 cell lytic effects was measured by MTT assay . The level of HIV-1 p24 antigen in acute and chronic HIV-1 infection was assayed by ELISA. HIV-1 reverse transcriptase and protease activites in vitro were tested by ELISA and FRET, respectively. Results QSL markedly inhibited syncytium formation induced by HIV-1 ⅢB , protected HIV-1 ⅢB induced MT-4 cell lytic effects and blocked cell-to-cell fusion. It also showed obviously inhibitory effect on the clinical strain HIV-1KM018 ancl drug resistant strain HIV-174V replication.QSL maybe inhibited HIV-I replication through multiple targets, including reverse transcriptase , protease and virus entry. Conclusion QSL is a Chinese medicine effective fraction formula with potent anti-HIV-1 activities.

  10. HIV-miR-H1 evolvability during HIV pathogenesis

    Lamers, Susanna L.; Fogel, Gary B.; Michael S McGrath

    2010-01-01

    The discovery of microRNAs (miRNAs) in viruses has generated considerable attention into their functional relevance in processes such as cell death, viral proliferation, and oncogenesis. Two early studies found no detectable miRNAs expressed within HIV; however, several studies have verified the existence and function of three HIV miRNAs, most notably HIV-miR-TAR, thus making the earlier results controversial. Although miRNAs are highly conserved within most species, HIV is known to have a hi...

  11. Building Blocks for Personal Brands

    Thomas, Lisa Carlucci

    2011-01-01

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

  12. Scintigraphic visualization of 'Blocking' thyroid

    Full text: An important problem in nuclear endocrinology is 'blocking' of thyroid gland, which necessitates postpone of the investigation, adverse clinical effect of stopping medications and a delay of making diagnosis. The aim of the study was to introduce and to determine the clinical value of the scintigraphy with 99mTc-MIBI in patients (Pts) with 'blocked thyroid'. In 365 Pts (aged 38-75 years), indicated for a thyroid scintigraphy after proper preparation, an investigation was performed with 74 MBq 99mTc-pertechnetate, 20 min. p.i. In 14 of them (3.8%), the thyroid was 'blocked' and additional scintigraphy was done with 370-555 MBq 99mTc-MIBI, 15 and 120 min.p.i. It was estimated that in all Pts there was a visualization of thyroid. In 1 of them, a large 'hot' nodule was visualized in the early and late image. Later on a differentiated thyroid carcinoma was proved histologically. In the rest of the patients 'cold' nodules with different size were visualized, eventually as a result of cysts. As a conclusion we consider, that a scintigraphy with 99mTc-MIBI is a useful tool in Pts with 'blocked' thyroid. In addition an evaluation of the thyroid nodule could be done and therefore- a recommendation for therapy

  13. Building block filtering and mixing

    Kemenade, C.H.M. van

    1998-01-01

    A three-stage evolutionary method, the BBF-GA is introduced. BBF-GA is an acronym for building block filtering genetic algorithm. During the first stage, an ensemble of fast evolutionary algorithms is used to explore the search space. The best individual found by each of these evolutionary algorithm

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

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

    2016-01-01

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

  15. Oral Complications of HIV Disease

    Leao, Jair C.; Camila M. B. Ribeiro; Carvalho, Alessandra A. T.; Cristina Frezzini; Stephen Porter

    2009-01-01

    Oral lesions are among the early signs of HIV infection and can predict its progression to acquired immunodeficiency syndrome (AIDS). A better understanding of the oral manifestations of AIDS in both adults and children has implications for all health care professionals. The knowledge of such alterations would allow for early recognition of HIV-infected patients. The present paper reviews epidemiology, relevant aspects of HIV infection related to the mouth in both adults and children, as well...

  16. Family Wellness, Not HIV Prevention

    Rotheram-Borus, Mary Jane; Swendeman, Dallas; Flannery, Diane

    2009-01-01

    HIV exceptionalism (and disease-specific programs generally) garner both unbalanced funding and the most talented personnel, distorting local health priorities. In support of HIV exceptionalism, the successful mobilization of significant global health sector resources was not possible prior to HIV. Both sides of the debate have merits; rather than perpetuating polarization, we suggest that sustained improvements in global health require creating a prevention infrastructure to meet multiple he...

  17. Hyperthermia stimulates HIV-1 replication.

    Ferdinand Roesch; Oussama Meziane; Anna Kula; Sébastien Nisole; Françoise Porrot; Ian Anderson; Fabrizio Mammano; Ariberto Fassati; Alessandro Marcello; Monsef Benkirane; Olivier Schwartz

    2012-01-01

    International audience HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C) on HIV-1 infection has not been extensively inve...

  18. HIV-1 Antiretroviral Drug Therapy

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with ...

  19. HIV: Social and Environmental Factors

    2012-02-01

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

  20. National HIV/AIDS Strategy

    2012-02-01

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

  1. Ocular manifestations of HIV infection.

    Jabs, D A

    1995-01-01

    OBJECTIVE: To evaluate the frequency of ocular complications and the clinical outcomes of these complications in patients with various stages of HIV infection. METHODS: Retrospective review of all HIV-infected patients seen in an AIDS ophthalmology clinic from November 1983 through December 31, 1992. RESULTS: Eleven-hundred sixty-three patients were seen for ophthalmologic evaluation. Of these, 781 had the acquired immune deficiency syndrome (AIDS), 226 had symptomatic HIV infection (AIDs-rel...

  2. Innovative masonry blocks for partition walls

    Vasconcelos, Graça; Poletti, Elisa; Medeiros, Pedro; Mendonça, Paulo; Carvalho, Pedro; Cunha, Sandra Raquel Leite; Camões, Aires; Lourenço, Paulo B.

    2010-01-01

    This paper intends to propose a non structural system of partition walls with monolithic blocks based on a composite material resulting from an admixture of cork and textile fibers combined with a non cement binder, gypsum. These blocks consist of two half blocks which have to be connected during laying process. The developed blocks were first tested under compressive and flexural loading in order to derive their mechanical behaviour. Different curing conditions were applied to the blocks dur...

  3. Endoscopic sphenopalatine ganglion block for pain relief

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

    1998-01-01

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

  4. Block Algorithms for Quark Propagator Calculation

    Pickles, Stephen M.; Collaboration, UKQCD

    1997-01-01

    Computing quark propagators in lattice QCD is equivalent to solving large, sparse linear systems with multiple right-hand sides. Block algorithms attempt to accelerate the convergence of iterative Krylov-subspace methods by solving the multiple systems simultaneously. This paper compares a block generalisation of the quasi-minimal residual method (QMR), Block Conjugate Gradient on the normal equation, Block Lanczos and ($\\gamma_5$-symmetric) Block BiConjugate Gradient.

  5. HIV testing, staging, and evaluation.

    Rodriguez, Carla V; Horberg, Michael A

    2014-09-01

    HIV testing and incidence are stable, but trends for certain populations are concerning. Primary prevention must be reinvigorated and target vulnerable populations. Science and policy have progressed to improve the accuracy, speed, privacy, and affordability of HIV testing. More potent and much better tolerated HIV treatments and a multidisciplinary approach to care have increased adherence and viral suppression. Changes to health care law in the United States seek to expand the affordability and access of improved HIV diagnostics and treatment. Continued challenges include improving long-term outcomes in people on lifetime regimens, reducing comorbidities associated with those regimens, and preventing further transmission. PMID:25151560

  6. Bromodomain Proteins in HIV Infection

    Melanie Ott

    2013-06-01

    Full Text Available Bromodomains are conserved protein modules of ~110 amino acids that bind acetylated lysine residues in histone and non-histone proteins. Bromodomains are present in many chromatin-associated transcriptional regulators and have been linked to diverse aspects of the HIV life cycle, including transcription and integration. Here, we review the role of bromodomain-containing proteins in HIV infection. We begin with a focus on acetylated viral factors, followed by a discussion of structural and biological studies defining the involvement of bromodomain proteins in the HIV life cycle. We end with an overview of promising new studies of bromodomain inhibitory compounds for the treatment of HIV latency.

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

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

    2015-01-01

    BACKGROUND AND OBJECTIVES: The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. METHODS: Sixteen...... healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated into a...... medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block and...

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

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

    2011-01-01

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

  9. Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro

    HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1IIIB entry and replication with EC50 values of 3.92 ± 0.62 and 6.59 ± 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1KM018 with EC50 values of 44.44 ± 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC50 value of 3.04 ± 1.20 nM. It also inhibited HIV-2ROD and HIV-2CBL-20 entry and replication in the μM range. Notably, HR212 was highly effective against T20-resistant strains with EC50 values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants

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

    Mingshun Zhang

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

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

    Li Yun-Yao

    2002-11-01

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

  12. Intercellular adhesion molecule 1 promotes HIV-1 attachment but not fusion to target cells.

    Naoyuki Kondo

    Full Text Available Incorporation of intercellular adhesion molecule 1 (ICAM-1 into HIV-1 particles is known to markedly enhance the virus binding and infection of cells expressing lymphocyte function-associated antigen-1 (LFA-1. At the same time, ICAM-1 has been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1 entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted HIV-1 attachment to cells in a temperature-dependent manner. It exerted a marginal effect on virus binding in the cold, but enhanced binding up to 4-fold at physiological temperature. ICAM-1-independent attachment in the cold was readily reversible upon subsequent incubation at elevated temperature, whereas ICAM-1-bearing particles were largely retained by cells. The better virus retention resulted in a proportional increase in HIV-1 internalization and fusion, suggesting that ICAM-1 did not specifically accelerate endocytosis or fusion steps. We also measured the rates of CD4 engagement, productive endocytosis and HIV-endosome fusion using specific fusion inhibitors. These rates were virtually independent of the presence of ICAM-1 in viral particles. Importantly, irrespective of the presence of ICAM-1, HIV-1 escaped from the low temperature block, which stopped virus endocytosis and fusion, much later than from a membrane-impermeant fusion inhibitor targeting surface-accessible particles. This result, along with the complete inhibition of HIV-1 fusion by a small molecule dynamin inhibitor, implies this virus enters lymphoid cells used in this study via endocytosis and that this pathway is not altered by the viral ICAM-1. Our data highlight the role of ICAM-1 in stabilizing the HIV-1 attachment to LFA-1 expressing cells, which leads to a proportional enhancement of the receptor-mediated uptake and fusion with endosomes.

  13. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication.

    Thenin-Houssier, Suzie; de Vera, Ian Mitchelle S; Pedro-Rosa, Laura; Brady, Angela; Richard, Audrey; Konnick, Briana; Opp, Silvana; Buffone, Cindy; Fuhrmann, Jakob; Kota, Smitha; Billack, Blase; Pietka-Ottlik, Magdalena; Tellinghuisen, Timothy; Choe, Hyeryun; Spicer, Timothy; Scampavia, Louis; Diaz-Griffero, Felipe; Kojetin, Douglas J; Valente, Susana T

    2016-04-01

    The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. PMID:26810656

  14. Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

    Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide DC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While DC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1α to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of DC13 implies additional mode(s) of action. These results suggest that DC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors

  15. Persistent HIV-1 replication maintains the tissue reservoir during therapy.

    Lorenzo-Redondo, Ramon; Fryer, Helen R; Bedford, Trevor; Kim, Eun-Young; Archer, John; Kosakovsky Pond, Sergei L; Chung, Yoon-Seok; Penugonda, Sudhir; Chipman, Jeffrey G; Fletcher, Courtney V; Schacker, Timothy W; Malim, Michael H; Rambaut, Andrew; Haase, Ashley T; McLean, Angela R; Wolinsky, Steven M

    2016-02-01

    Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy. PMID:26814962

  16. Inhibiting the HIV integration process: past, present, and the future.

    Di Santo, Roberto

    2014-02-13

    HIV integrase (IN) catalyzes the insertion into the genome of the infected human cell of viral DNA produced by the retrotranscription process. The discovery of raltegravir validated the existence of the IN, which is a new target in the field of anti-HIV drug research. The mechanism of catalysis of IN is depicted, and the characteristics of the inhibitors of the catalytic site of this viral enzyme are reported. The role played by the resistance is elucidated, as well as the possibility of bypassing this problem. New approaches to block the integration process are depicted as future perspectives, such as development of allosteric IN inhibitors, dual inhibitors targeting both IN and other enzymes, inhibitors of enzymes that activate IN, activators of IN activity, as well as a gene therapy approach. PMID:24025027

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

    Pestana, Jennifer

    2014-01-01

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

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

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

    2014-01-20

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

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

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

  20. A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread.

    Dropulić, B; Hĕrmánková, M; Pitha, P M

    1996-01-01

    Defective-interfering viruses are known to modulate virus pathogenicity. We describe conditionally replicating HIV-1 (crHIV) vectors that interfere with wild-type HIV-1 (wt-HIV) replication and spread. crHIV vectors are defective-interfering HIV genomes that do not encode viral proteins and replicate only in the presence of wt-HIV helper virus. In cells that contain both wt-HIV and crHIV genomes, the latter are shown to have a selective advantage for packaging into progeny virions because the...

  1. HIV Behavioral Research Online

    Chiasson, Mary Ann; Parsons, Jeffrey T.; Tesoriero, James M.; Carballo-Dieguez, Alex; Hirshfield, Sabina; Remien, Robert H.

    2006-01-01

    Internet access has caused a global revolution in the way people of all ages and genders interact. Many have turned to the Internet to seek love, companionship, and sex, prompting researchers to move behavioral studies online. The sexual behavior of men who have sex with men (MSM) has been more closely studied than that of any other group online given the abundance of gay-oriented websites and concerns about increasing transmission of HIV and other sexually transmitted infections. Not only do...

  2. Psychotropic Drugs and HIV

    Ana-Lúcia Moreira; Melinda Carmen Godinho Pereira; Diogo Telles-Correia

    2014-01-01

    Background: HIV/AIDS infection is frequently associated with psychiatric disor- ders like psychosis, depression and anxiety. Psychiatric comorbidities may interfere with adherence to antiretroviral treatment. Therefore, diagnosis and treatment of these conditions are essential. However, the administration of a psychotropic drug to HAART therapy can result in drug interactions.Objectives: This review aims to analyze the various psychotropic drugs that can be used in these patients, as well as ...

  3. HIV stigma among substance abusing people living with HIV/AIDS: implications for HIV treatment.

    Levi-Minzi, Maria A; Surratt, Hilary L

    2014-08-01

    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 (54.7%) were associated with higher HIV stigma across all domains. 49.9% of the sample reported antiretroviral (ARV) medication diversion (the unlawful sale and trading of ARV medications); diverters endorsed significantly higher stigma related to disclosure. 54.1% of the sample reported ≥95% ARV adherence; these individuals reported significantly lower stigma for self-acceptance, disclosure, and social relationships. Multivariate linear regression showed that depression and social support demonstrated significant main effects across stigma domains. Findings suggest that interventions to decrease HIV related stigma may be an important component of initiatives to increase engagement in HIV care. PMID:24983302

  4. Emplacement of small and large buffer blocks

    The report describes emplacement of a buffer structure encircling a spent fuel canister to be deposited in a vertical hole. The report deals with installability of various size blocks and with an emplacement gear, as well as evaluates the achieved quality of emplacement and the time needed for installing the buffer. Two block assembly of unequal size were chosen for examination. A first option involved small blocks, the use of which resulted in a buffer structure consisting of small sector blocks 200 mm in height. A second option involved large blocks, resulting in a buffer structure which consists of eight blocks. In these tests, the material chosen for both block options was concrete instead of bentonite. The emplacement test was a three-phase process. A first phase included stacking a two meter high buffer structure with small blocks for ensuring the operation of test equipment and blocks. A second phase included installing buffer structures with both block options to a height matching that of a canister-encircling cylindrical component. A third phase included testing also the installability of blocks to be placed above the canister by using small blocks. In emplacement tests, special attention was paid to the installability of blocks as well as to the time required for emplacement. Lifters for both blocks worked well. Due to the mass to be lifted, the lifter for large blocks had a more heavy-duty frame structure (and other lifting gear). The employed lifters were suspended in the tests on a single steel wire rope. Stacking was managed with both block sizes at adequate precision and stacked-up towers were steady. The stacking of large blocks was considerably faster. Therefore it is probably that the overall handling of the large blocks will be more convenient at a final disposal site. From the standpoint of reliability in lifting, the small blocks were safer to install above the canister. In large blocks, there are strict shape-related requirements which are

  5. An HIV-Preventive Intervention for Youth Living with HIV

    Lightfoot, Marguerita; Rotheram-Borus, Mary Jane; Tevendale, Heather

    2007-01-01

    As the number of youth infected with HIV rises, secondary prevention programs are needed to help youth living with HIV meet three goals: (1) increase self-care behaviors, medical adherence, and health-related interactions; (2) reduce transmission acts; and (3) enhance their quality of life. This article describes an intervention program for youth…

  6. Punica granatum (Pomegranate juice provides an HIV-1 entry inhibitor and candidate topical microbicide

    Li Yun-Yao

    2004-10-01

    Full Text Available Abstract Background For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Methods Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1 infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2 binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. Results HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Conclusion These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.

  7. Compact planar microwave blocking filters

    U-Yen, Kongpop (Inventor); Wollack, Edward J. (Inventor)

    2012-01-01

    A compact planar microwave blocking filter includes a dielectric substrate and a plurality of filter unit elements disposed on the substrate. The filter unit elements are interconnected in a symmetrical series cascade with filter unit elements being organized in the series based on physical size. In the filter, a first filter unit element of the plurality of filter unit elements includes a low impedance open-ended line configured to reduce the shunt capacitance of the filter.

  8. Multi-level block permutation.

    Winkler, Anderson M; Webster, Matthew A; Vidaurre, Diego; Nichols, Thomas E; Smith, Stephen M

    2015-12-01

    Under weak and reasonable assumptions, mainly that data are exchangeable under the null hypothesis, permutation tests can provide exact control of false positives and allow the use of various non-standard statistics. There are, however, various common examples in which global exchangeability can be violated, including paired tests, tests that involve repeated measurements, tests in which subjects are relatives (members of pedigrees) - any dataset with known dependence among observations. In these cases, some permutations, if performed, would create data that would not possess the original dependence structure, and thus, should not be used to construct the reference (null) distribution. To allow permutation inference in such cases, we test the null hypothesis using only a subset of all otherwise possible permutations, i.e., using only the rearrangements of the data that respect exchangeability, thus retaining the original joint distribution unaltered. In a previous study, we defined exchangeability for blocks of data, as opposed to each datum individually, then allowing permutations to happen within block, or the blocks as a whole to be permuted. Here we extend that notion to allow blocks to be nested, in a hierarchical, multi-level definition. We do not explicitly model the degree of dependence between observations, only the lack of independence; the dependence is implicitly accounted for by the hierarchy and by the permutation scheme. The strategy is compatible with heteroscedasticity and variance groups, and can be used with permutations, sign flippings, or both combined. We evaluate the method for various dependence structures, apply it to real data from the Human Connectome Project (HCP) as an example application, show that false positives can be avoided in such cases, and provide a software implementation of the proposed approach. PMID:26074200

  9. Rhesus TRIM5α Disrupts the HIV-1 Capsid at the Inter­Hexamer Interfaces

    Zhao, Gongpu; Ke, Danxia; Vu, Thomas; Ahn, Jinwoo; Shah, Vaibhav B.; Yang, Ruifeng; Aiken, Christopher; Charlton, Lisa M.; Gronenborn, Angela M.; Zhang, Peijun

    2011-01-01

    TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully und...

  10. Discovery and Assesment of New Target Sites for Anti-HIV Therapies

    Breward, Chris; Heffernan, Jane; Robert M., Miura; Madras, Neal; Ockendon, John; Sørensen, Mads Peter; Anderssen, Robert; Melnik, Roderick; Mcguinness, Mark; Qazi, Sanjive

    2008-01-01

    The HIV viruses infect cells by endocytosis and takes over parts of the cells reaction pathways in order to reproduce itself and spread the infection. One such pathway is the mammalian inflammatory signaling, which invoke NF-κB as the principal transcription factor. A treatment against HIV could be based on blocking the NF-κB pathway by a suitably designed drug. The aim of the current project is to investigate the feasibility of this idea by using mathematical modelling of the NF-κB pathway.

  11. Characteristics, Immunological Response & Treatment Outcomes of HIV-2 Compared with HIV-1 & Dual Infections (HIV 1/2) in Mumbai

    Chiara, Montaldo; Rony, Zachariah; Homa, Mansoor; Bhanumati, Varghese; Ladomirska, Joanna; Manzi, M.; Wilson, N; Alaka, Deshpande; Harries, A. D.

    2010-01-01

    Background & objectives: Information available on HIV-2 and dual infection (HIV-1/2) is limited. This study was carried out among HIV positive individuals in an urban referral clinic in Khar, Mumbai, India, to report on relative proportions of HIV-1, HIV-2 and HIV-1/2 and baseline characteristics, response to and outcomes on antiretroviral treatment (ART). Methods: Retrospective analysis of programme data (May 2006-May 2009) at Khar HIV/AIDS clinic at Mumbai, India was done. Three test algori...

  12. A conformal block Farey tail

    Maloney, Alexander; Ng, Gim Seng

    2016-01-01

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

  13. Interfaces between Block Copolymer Domains

    Kim, Jaeup; Jeong, Seong-Jun; Kim, Sang Ouk

    2011-03-01

    Block copolymers naturally form nanometer scale structures which repeat their geometry on a larger scale. Such a small scale periodic pattern can be used for various applications such as storage media, nano-circuits and optical filters. However, perfect alignment of block copolymer domains in the macroscopic scale is still a distant dream. The nanostructure formation usually occurs with spontaneously broken symmetry; hence it is easily infected by topological defects which sneak in due to entropic fluctuation and incomplete annealing. Careful annealing can gradually reduce the number of defects, but once kinetically trapped, it is extremely difficult to remove all the defects. One of the main reasons is that the defect finds a locally metastable morphology whose potential depth is large enough to prohibit further morphology evolution. In this work, the domain boundaries between differently oriented lamellar structures in thin film are studied. For the first time, it became possible to quantitatively study the block copolymer morphology in the transitional region, and it was shown that the twisted grain boundary is energetically favorable compared to the T-junction grain boundary. [Nano Letters, 9, 2300 (2010)]. This theoretical method successfully explained the experimental results.

  14. [THE TECHNOLOGY "CELL BLOCK" IN CYTOLOGICAL PRACTICE].

    Volchenko, N N; Borisova, O V; Baranova, I B

    2015-08-01

    The article presents summary information concerning application of "cell block" technology in cytological practice. The possibilities of implementation of various modern techniques (immune cytochemnical analysis. FISH, CISH, polymerase chain reaction) with application of "cell block" method are demonstrated. The original results of study of "cell block" technology made with gelatin, AgarCyto and Shadon Cyoblock set are presented. The diagnostic effectiveness of "cell block" technology and common cytological smear and also immune cytochemical analysis on samples of "cell block" technology and fluid cytology were compared. Actually application of "cell block" technology is necessary for ensuring preservation of cell elements for subsequent immune cytochemical and molecular genetic analysis. PMID:26596046

  15. Some new construction methods of variance balanced block designs with repeated blocks

    Ceranka, Bronisław; Graczyk, Małgorzata

    2014-01-01

    Some new construction methods of the variance balanced block designs with repeated blocks are given. They are based on the specialized product of incidence matrices of the balanced incomplete block designs.

  16. How you get HIV/AIDS

    How you get HIV/AIDS Which body fluids contain HIV? HIV is a virus that lives in blood and other fluids in the body. Moving ... answers to any questions you have about HIV/AIDS. Your public health department and health care provider ...

  17. Fotodegradovatelné inhibitory HIV proteasy

    Schimer, Jiří; Pávová, Marcela; Prouzová, Hana; Weber, Jan; Cígler, Petr; Majer, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 108, č. 5 (2014), s. 549. ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků /14./. 13.05.2014-16.05.2014, Milovy] Institutional support: RVO:61388963 Keywords : HIV protease * HIV PR inhibitors * Caged HIV Pr * HIV maturation Subject RIV: CE - Biochemistry

  18. Drugs + HIV, Learn the Link

    Full Text Available ... prevention clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and ... HIV/AIDS : This site provides information both for health care providers and for Veterans and the public. Past ...

  19. Drugs + HIV, Learn the Link

    Full Text Available ... Children & Teens Search Connect with NIDA : Google Plus Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs ... HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug abuse ...

  20. HIV/AIDS and Pregnancy

    If you have HIV/AIDS and find out you are pregnant or think you may be pregnant, you should let your health care provider know as soon as possible. Some HIV/AIDS medicines may harm your baby. Your health ...

  1. Drugs + HIV, Learn the Link

    Full Text Available ... can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood cell that is crucial to the normal function of the human immune system. Loss of these CD4+ cells in people with ...

  2. Drugs + HIV, Learn the Link

    Full Text Available ... gov New Media Tools : These new media tools offer new ways to deliver HIV/AIDS information to ... U.S. Department of Health and Human Services (HHS), offers access to the latest, federally approved HIV/AIDS ...

  3. Drugs + HIV, Learn the Link

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

  4. Drugs + HIV, Learn the Link

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

  5. Drugs + HIV, Learn the Link

    Full Text Available ... the message to young people and to parents, teachers, and the media about the link between drug abuse and HIV. We have produced a set of ... the message to young people and to parents, teachers, and the media about the link between drug abuse and HIV. Post on Facebook or Twitter ; add ...

  6. Drugs + HIV, Learn the Link

    ... the message to young people and to parents, teachers, and the media about the link between drug abuse and HIV. We have produced a set of ... the message to young people and to parents, teachers, and the media about the link between drug abuse and HIV. Post on Facebook or Twitter ; add ...

  7. Drugs + HIV, Learn the Link

    Full Text Available ... with HIV is a key predictor of the development of AIDS. Because of their compromised immune system, ... at: https://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  8. Drugs + HIV, Learn the Link

    Full Text Available ... party and under the influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ... young adults that non-injection drug use and alcohol use can lead to poor ... behaviors and HIV infection. Although the characters are fictional, ...

  9. Drugs + HIV, Learn the Link

    Full Text Available ... info. nih.gov : AIDSinfo, a service of the U.S. Department of Health and Human Services (HHS), offers ... affected by HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized ...

  10. HIV Testing among Detained Youth

    Voisin, Dexter R.; Salazar, Laura F.; Crosby, Richard; DiClemente, Ralph J.; Yarber, William L.; Staples-Horne, Michelle

    2004-01-01

    Published reports have not investigated the issue of voluntary HIV testing among detained youth, a population disproportionately infected with HIV compared to other adolescent groups. Data were collected from 467 sexually active detained adolescents in Georgia on demographic, environmental, and drug and sexual history variables, to explore…

  11. Drugs + HIV, Learn the Link

    Full Text Available ... gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, National Center ... services, and referrals for medical and social services. Reference Marcondes, M.C. et al. “Methamphetamine increases brain ...

  12. 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 ... DC Department of Health AIDS Arms, Inc. National Community Center of Excellence in Women’s Health National Women’s ...

  13. Syphilis in the HIV Era

    Kassutto, Sigall; Doweiko, John P.

    2004-01-01

    The incidence of syphilis has consistently increased from 2000 to 2002. We report a case of acquired syphilis with symptoms of Tullio phenomenon in a patient concurrently diagnosed with HIV infection. The resurgence of syphilis in HIV-positive groups at high risk has public health implications for prevention of both diseases.

  14. Drugs + HIV, Learn the Link

    Full Text Available ... public service ads (PSA) where an HIV-positive teenager recounts the night she went to a party and under the influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ...

  15. Drugs + HIV, Learn the Link

    Full Text Available ... HIV patients who do not abuse drugs. In animal studies, methamphetamine has been shown to increase the amount of HIV in brain cells 1 . Drug abuse treatment. Since the late 1980s, research has shown that treating drug abuse is an ...

  16. Jamie Foxx Talks About HIV

    2012-07-24

    Jamie Foxx, Academy Award winning actor and singer, 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. HIV/AIDS and Pregnancy

    If you have HIV/AIDS and find out you are pregnant or think you may be pregnant, you should let your health care provider know as soon as possible. Some HIV/AIDS medicines may harm your baby. Your health care ...

  18. Encephalitis in primary HIV infection

    Helleberg, M; Kirk, O

    2013-01-01

    We report a case of primary HIV encephalitis, which initially presented as acute psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis and multiple infarctions, whereas a brain biopsy after six weeks of symptoms showed HIV encephalitis with microglial nodules, but no sig...

  19. Drugs + HIV, Learn the Link

    Full Text Available ... gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/AIDS and Drug Abuse: Intertwined ... Press Office Meetings & Events Media Guide Get this Publication Español View Webisodes View Videos "After the Party" " ...

  20. Drugs + HIV, Learn the Link

    Full Text Available ... HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. ... NIDA TV PEERx Drugs & Health Blog The NIDA Science Fair Award for Addiction Science USA Science & Engineering ...

  1. An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activity

    Borrego, Pedro; Calado, Rita; Marcelino, José M.; Pereira, Patrícia MR; Quintas, Alexandre; Barroso, Helena; Taveira, Nuno

    2013-01-01

    "Objectives: To produce new fusion inhibitor peptides for HIV-1 and HIV-2 based on ancestral envelope sequences. Methods: HIV-2/simian immunodeficiency virus (SIV) ancestral transmembrane protein sequences were reconstructed and ancestral peptides were derived from the helical region 2 (HR2). The activity of one ancestral peptide (named P3) was examined against a panel of HIV-1 and HIV-2 primary isolates in TZM-bl cells and peripheral blood mononuclear cells and compared to ...

  2. Impact of HIV-1, HIV-2 and HIV-1+2 dual infection on the outcome of tuberculosis

    Wejse, C; Patsche, C B; Kühle, A;

    2014-01-01

    BACKGROUND: HIV-1 infection has been shown to impact the outcome of patients with tuberculosis (TB), but data regarding the impact of HIV-2 on TB outcomes are limited. The aim of this study was to assess the impact of HIV types on mortality among TB patients in Guinea-Bissau and to examine the...... predictive ability of the TBscoreII, a clinical score used to assess disease severity. METHODS: In a prospective follow-up study, we examined the prevalence of HIV-1, HIV-2, and HIV-1+2 co-infection in TB patients in Guinea-Bissau, and the impact on outcomes at 12 months of follow-up. We included all adult...... seventy-nine patients were HIV-infected: 241 had HIV-1, 93 had HIV-2, and 45 were HIV-1+2 dual infected. The HIV type-associated risk of TB was 6-fold higher for HIV-1, 7-fold higher for HIV-1+2 dual infection, and 2-fold higher for HIV-2 compared with the HIV-uninfected. Of the patients included, 144 (11...

  3. Is an HIV vaccine possible?

    Nancy A. Wilson

    2009-08-01

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  4. Using Quilt Blocks to Construct Understanding

    Westegaard, Susanne K.

    2008-01-01

    The article documents student experiences with quilt blocks in a mathematics classroom. Using blocks as tools, students construct their understanding of perimeter, area, probability, and transformations. (Contains 9 figures.)

  5. High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

    Jacobson, Kathleen R; Arora, Sanjay; Walsh, Kristin B; Lora, Meredith; Merjavy, Stephen; Livermore, Shanna; Menchine, Michael

    2016-07-01

    Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum. PMID:27028498

  6. Rapid HIV Testing in Large Urban Jails

    Beckwith, Curt G.; Nunn, Amy; Baucom, Sharon; Getachew, Asresahegn; Akinwumi, Akin; Herdman, Bruce; DiBartolo, Phil; Spencer, Susan; Brown, Devon; Lesansky, Henry; Kuo, Irene

    2012-01-01

    HIV prevalence is higher in jails than in the community, yet many jails do not conduct HIV testing. Jails in Baltimore, Maryland; Philadelphia, Pennsylvania; and the District of Columbia have implemented innovative rapid HIV testing programs. We have summarized the results of these programs, including the numbers of persons tested, rapid and confirmatory HIV test results, and numbers of persons newly diagnosed with HIV. We have described facilitators and challenges of implementation. These pr...

  7. Nutrition and HIV-Positive Pregnancy

    Montgomery, Kristen S.

    2003-01-01

    When an HIV-positive woman becomes pregnant, additional nutritional considerations are warranted. Compared to routine prenatal nutritional assessment and intervention, pregnant HIV-positive women have increased needs to promote a healthy outcome. This column contains information on HIV and pregnancy, nutrition and infection, and nutrition for HIV-positive pregnancy. This content can be integrated into childbirth education settings to improve care to women who are HIV-positive.

  8. HIV Testing, Subjective Beliefs and Economic Behavior

    Rebecca L. Thornton

    2012-01-01

    This paper examines the effects of learning HIV status on economic behavior among rural Malawians. According to economic life-cycle models, if learning HIV results is informative about additional years of life, being diagnosed HIV-positive or negative should predict changes in consumption, investment and savings behavior with important micro and macro-economic implications. Using an experiment that randomly assigned incentives to learn HIV results, I find that while learning HIV results had s...

  9. Persistent HIV-1 replication during antiretroviral therapy

    Martinez-Picado, Javier; Deeks, Steven G

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on ef...

  10. HIV, opiates and enteric neuron dysfunction

    Galligan, James J.

    2015-01-01

    HIV is an immunosuppressive virus that targets CD4+ T-lymphocytes. HIV infections cause increased susceptibility to opportunistic infections and cancer. HIV infection can also alter central nervous system (CNS) function causing cognitive impairment. HIV does not infect neurons but it does infect astrocytes and microglia in the CNS. HIV can also infect enteric glia initiating an intestinal inflammatory response which causes enteric neural injury and gut dysfunction. Part of the inflammatory re...

  11. Reducing mother-to-child HIV transmission

    2001-01-01

    In developing countries,mother-to-child trans mission of human immune deficiency virus (HIV)is responsible for 5 to 10 percen t o f all new HIV infections.Most children born to HIV-positive mothers are not HIV positive,but one quarter to one third are.The following instert looks at the p o ssibilities for reducing mother-to-child HIV transmission,and discusses some of the questions that are still unanswered.

  12. Multigrid Methods for General Block Toeplitz Matrices

    Thomas Huckle; Jochen Staudacher

    2016-01-01

    In this paper we discuss multigrid methods for symmetric positive definite Block Toeplitz matrices. Our Block Toeplitz systems are general in the sense that the individual blocks are not necessarily Toeplitz. We investigate how transfer operators for prolongation and restriction have to be chosen such that our multigrid algorithms converge quickly. We will point out why these transfer operators can be understood as block matrices as well. We explain how our new algorithms can also be combined...

  13. Reward, attention, and HIV-related risk in HIV+ individuals.

    Anderson, Brian A; Kronemer, Sharif I; Rilee, Jessica J; Sacktor, Ned; Marvel, Cherie L

    2016-08-01

    Human immunodeficiency virus (HIV) is often contracted through engaging in risky reward-motivated behaviors such as needle sharing and unprotected sex. Understanding the factors that make an individual more vulnerable to succumbing to the temptation to engage in these risky behaviors is important to limiting the spread of HIV. One potential source of this vulnerability concerns the degree to which an individual is able to resist paying attention to irrelevant reward information. In the present study, we examine this possible link by characterizing individual differences in value-based attentional bias in a sample of HIV+ individuals with varying histories of risk-taking behavior. Participants learned associations between experimental stimuli and monetary reward outcome. The degree of attentional bias for these reward-associated stimuli, reflected in their ability to capture attention when presented as task-irrelevant distractors, was then assessed both immediately and six months following reward learning. Value-driven attentional capture was related to substance abuse history and non-planning impulsiveness during the time leading up to contraction of HIV as measured via self-report. These findings suggest a link between the ability to ignore reward-associated information and prior HIV-related risk-taking behavior. Additionally, particular aspects of HIV-associated neurocognitive disorders were related to attentional bias, including motor deficits commonly associated with HIV-induced damage to the basal ganglia. PMID:26484383

  14. Occurrence of Pregnancies among HIV Infected Indian Women: Does Knowledge about HIV Status Make a Difference?

    Shrinivas Darak; Inge Hutter; Sanjeevani Kulkarni; Vinay Kulkarni; Fanny Janssen

    2015-01-01

    textabstractThis is the first study to examine the behavioural effect of HIV on fertility among HIV infected women in India. Retrospective calendar data from ever-married HIV infected women between 15 and 45 years of age, attending a specialized HIV clinic in Pune, Western India (N = 560), were analysed. Directly standardized overall and parity-specific pregnancy rates were compared among HIV infected women before and after coming to know about their HIV status. The age- and parity-standardiz...

  15. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Nair, Madhavan P.N.; Zainulabedin Saiyed; Saxena, Shailendra K; Sudheesh Pilakka-Kanthikeel; Pichili Vijaya Bhaskar Reddy

    2012-01-01

    HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest th...

  16. The role of enacted stigma in parental HIV disclosure among HIV-infected parents in China

    Qiao, Shan; Li, Xiaoming; Zhou, Yuejiao; Shen, Zhiyong; Tang, Zhenzhu; Stanton, Bonita

    2015-01-01

    Existing studies have delineated that HIV-infected parents face numerous challenges in disclosing their HIV infection to the children (“parental HIV disclosure”), and practices of parental HIV disclosure vary with individual characteristics, family contexts, and social environment. Using cross-sectional data from 1254 HIV-infected parents who had children aged 5–16 years in southwest China, the current study examined the association of parental HIV disclosure with mental health and medication...

  17. Bullet-Block Science Video Puzzle

    Shakur, Asif

    2015-01-01

    A science video blog, which has gone viral, shows a wooden block shot by a vertically aimed rifle. The video shows that the block hit dead center goes exactly as high as the one shot off-center. (Fig. 1). The puzzle is that the block shot off-center carries rotational kinetic energy in addition to the gravitational potential energy. This leads a…

  18. New Considerations of Turbo Block Codes

    YUEDianwu; EdSHWEDYK

    2004-01-01

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

  19. 31 CFR 500.319 - Blocked account.

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 500.319 Section 500... § 500.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals of...

  20. 31 CFR 515.319 - Blocked account.

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 515.319 Section 515... § 515.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals or...

  1. Practical Binary Adaptive Block Coder

    Reznik, Yuriy A

    2007-01-01

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

  2. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

    In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5α with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain

  3. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges.

    Gautam, Rajeev; Nishimura, Yoshiaki; Pegu, Amarendra; Nason, Martha C; Klein, Florian; Gazumyan, Anna; Golijanin, Jovana; Buckler-White, Alicia; Sadjadpour, Reza; Wang, Keyun; Mankoff, Zachary; Schmidt, Stephen D; Lifson, Jeffrey D; Mascola, John R; Nussenzweig, Michel C; Martin, Malcolm A

    2016-05-01

    Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission. PMID:27120156

  4. Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein

    He Yukai

    2005-11-01

    Full Text Available Abstract Background A critical step in the production of new HIV virions involves the TAT protein binding to the TAR element. The TAT protein contains in close proximity its TAR RNA binding domain and protein transduction domain (PTD. The PTD domain of TAT has been identified as being instrumental in the protein's ability to cross mammalian cell and nuclear membranes. All together, this information led us to form the hypothesis that a protein containing the TAR RNA binding domain could compete with the native full length TAT protein and effectively block the TAR RNA binding site in transduced HIV infected cells. Results We synthesized a short peptide named Tat-P, which contained the TAR RNA binding and PTD domains to examine whether the peptide has the potential of inhibiting TAT dependent HIV replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV derived lentiviral vector model. We found that the TAT PTD domain not only efficiently transduced test cells, but also effectively inhibited the production of lentiviral particles in a TAT dependent manner. These results were also supported by data derived from the TAT activated LTR-luciferase expression model and RNA binding assays. Conclusion Tat-P may become part of a category of anti-HIV drugs that competes with full length TAT proteins to inhibit HIV replication. In addition, this study indicates that the HIV derived lentiviral vector system is a safe and reliable screening method for anti-HIV drugs, especially for those targeting the interaction of TAT and TAR RNAs.

  5. Identification of a Small Molecular Anti - HIV - 1 Compound that Interferes with Formation of the Fusion - active gp41 Core

    2001-01-01

    The human immunodeficiency virus type 1 (HIV - 1 ) envelope glycoprotein gp41 plays a critical role in the fusion of viral and target cell membranes. The gp41 extracellular domain, which contains fusion peptide (FP), N - and C - terminal hydrophobic heptad repeats (NHR and CHR, respectively). Peptides derived from NHR and CHR regions,designated N- and C- peptides, respectively, can interact with each other to form a six - stranded coiled - coil domain, representing the fusion-active gp41 core. Our previous studies demonstrated that the C- peptides have potent inhibitory activity against HIV- 1 infection.These peptides inhibit HIV- 1 -mediated membrane fusion by binding to NHR regions for preventing the formation of fusion- active gp41 core. One of the C - peptides, T - 20, which is in the phase Ⅲ clinical trails, is expected to become the first peptide HIV fusion inhibitory drug in the near future. However, this peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Therefore, it is essential to develop small molecular non -peptide HIV fusion inhibitors having similar mechanism of action as the C- peptides. We have established an ELISA- based screening assay using a unique monoclonal antibody, NC- 1, which can specifically bind to a conformational epitope on the gp41 core domain. Using this screening assay, we have identified a small molecular anti- HIV- 1 compound,named ADS-Jl, which inhibits HIV- 1- mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion - active gp41 core. This compound will be used as a lead to design and develop novel HIV fusion inhibitors as new drugs for the treatment of HIV infection and/or AIDS.

  6. Ergotismo y HIV

    Bárbara C. Finn; Sabrina Vadalá; Ana Meraldi; Julio E. Bruetman; Jorge V. Martínez; Pablo Young

    2013-01-01

    El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarro...

  7. Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

    Özkaya Şahin, Gülşen; Holmgren, Birgitta; da Silva, Zacarias; Nielsen, Jens; Nowroozalizadeh, Salma; Esbjörnsson, Joakim; Månsson, Fredrik; Andersson, Sören; Norrgren, Hans; Aaby, Peter; Jansson, Marianne; Fenyö, Eva Maria

    2012-01-01

    HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells a...

  8. Isostatic compression of buffer blocks. Middle scale

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

    2012-01-15

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

  9. Isostatic compression of buffer blocks. Middle scale

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

  10. HIV: Past, present and future

    Harindra V

    2008-01-01

    Full Text Available The origin of acquired immune deficiency syndrome (AIDS and human immunodeficiency virus (HIV has puzzled scientists ever since the illness first came to light in the early 1980s. For over 25 years it has been the subject of fierce debate and the cause of countless arguments. It is now generally accepted that HIV is a descendant of a simian immunodeficiency virus and there are many theories about how this ′zoonosis′ originated and how SIV became HIV in humans. Advances in treatment have steadily reduced the morbidity and mortality associated with HIV infection. However, in the low-income, high-prevalence countries, antiretroviral medication has taken a long time to reach the people who actually need it. Access to medication must greatly improve if millions of deaths are to be avoided. HIV is a preventable disease. Unless great progress is made in prevention, the number of people living with HIV will outstrip the resources available for treatment. The search for effective vaccines and microbicides must therefore be one of the very highest priorities. HIV is a global threat. Action needs to be taken to prevent it killing many more millions than those who have already died. This action needs not only to continue, but to be speeded up considerably.

  11. Thyroid blocking after nuclear accidents

    Following the Chernobyl accident a marked increase in thyroid cancer incidence among the children in Belarus, the Ukraine and Russia has been detected, strongly suggesting a causal relationship to the large amounts of radioactive iodine isotopes in the resulting fallout. Taking into account the Chernobyl experience the German Committee on Radiation Protection decided to reduce the intervention levels on the basis of the 1989 WHO recommendations and adopted a new concept concerning thyroid blocking in response to nuclear power plant accidents. Experimental animal studies and theoretical considerations show that thyroid blocking with potassium iodide (KI) in a dose of about 1.4 mg per kg body weight is most effective in reducing irradiation to the thyroid from the intake of radioiodine nuclides, provided KI is given within 2 hours after exposure. According to the new concept, persons over 45 years of age should not take iodine tablets because the drug could cause a greater health risk due to prevalent functional thyroid autonomy in this age group than the radioactive iodine averted by KI. On the basis of accident analysis and the new philosophy suitable distribution strategies and logistics are proposed and discussed. (orig.)

  12. Seismicity of the Jalisco Block

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

    2002-12-01

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

  13. Ganglion block. When and how?

    Increasing understanding of the anatomy and physiology of neural structures has led to the development of surgical and percutaneous neurodestructive methods in order to target and destroy various components of afferent nociceptive pathways. The dorsal root ganglia and in particular the ganglia of the autonomous nervous system are targets for radiological interventions. The autonomous nervous system is responsible for the regulation of organ functions, sweating, visceral and blood vessel-associated pain. Ganglia of the sympathetic chain and non-myelinized autonomous nerves can be irreversibly destroyed by chemical and thermal ablation. Computed tomography (CT)-guided sympathetic nerve blocks are well established interventional radiological procedures which lead to vasodilatation, reduction of sweating and reduction of pain associated with the autonomous nervous system. Sympathetic blocks are applied for the treatment of various vascular diseases including critical limb ischemia. Other indications for thoracic and lumbar sympathectomy include complex regional pain syndrome (CRPS), chronic tumor associated pain and hyperhidrosis. Neurolysis of the celiac plexus is an effective palliative pain treatment particularly in patients suffering from pancreatic cancer. Percutaneous dorsal root ganglion rhizotomy can be performed in selected patients with radicular pain that is resistant to conventional pharmacological and interventional treatment. (orig.)

  14. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

    Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NFκB. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFNγ, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator

  15. Why do HIV-1 and HIV-2 use different pathways to develop AZT resistance?

    2006-02-01

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 develops resistance to all available drugs, including the nucleoside analog reverse transcriptase inhibitors (NRTIs such as AZT. ATP-mediated excision underlies the most common form of HIV-1 resistance to AZT. However, clinical data suggest that when HIV-2 is challenged with AZT, it usually accumulates resistance mutations that cause AZT resistance by reduced incorporation of AZTTP rather than selective excision of AZTMP. We compared the properties of HIV-1 and HIV-2 reverse transcriptase (RT in vitro. Although both RTs have similar levels of polymerase activity, HIV-1 RT more readily incorporates, and is more susceptible to, inhibition by AZTTP than is HIV-2 RT. Differences in the region around the polymerase active site could explain why HIV-2 RT incorporates AZTTP less efficiently than HIV-1 RT. HIV-1 RT is markedly more efficient at carrying out the excision reaction with ATP as the pyrophosphate donor than is HIV-2 RT. This suggests that HIV-1 RT has a better nascent ATP binding site than HIV-2 RT, making it easier for HIV-1 RT to develop a more effective ATP binding site by mutation. A comparison of HIV-1 and HIV-2 RT shows that there are numerous differences in the putative ATP binding sites that could explain why HIV-1 RT binds ATP more effectively. HIV-1 RT incorporates AZTTP more efficiently than does HIV-2 RT. However, HIV-1 RT is more efficient at ATP-mediated excision of AZTMP than is HIV-2 RT. Mutations in HIV-1 RT conferring AZT resistance tend to increase the efficiency of the ATP-mediated excision pathway, while mutations in HIV-2 RT conferring AZT resistance tend to increase the level of AZTTP exclusion from the polymerase active site. Thus, each RT usually chooses the pathway best suited to extend the properties of the respective wild-type enzymes.

  16. Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme

    Veille Jean-Claude

    2006-05-01

    Full Text Available Abstract Background The high rate of HIV-1 mutation and increasing resistance to currently available antiretroviral (ART therapies highlight the need for new antiviral agents. Products derived from natural sources have been shown to inhibit HIV-1 replication during various stages of the virus life cycle, and therefore represent a potential source of novel therapeutic agents. To expand our arsenal of therapeutics against HIV-1 infection, we investigated aqueous extract from Sargassum fusiforme (S. fusiforme for ability to inhibit HIV-1 infection in the periphery, in T cells and human macrophages, and for ability to inhibit in the central nervous system (CNS, in microglia and astrocytes. Results S. fusiforme extract blocked HIV-1 infection and replication by over 90% in T cells, human macrophages and microglia, and it also inhibited pseudotyped HIV-1 (VSV/NL4-3 infection in human astrocytes by over 70%. Inhibition was mediated against both CXCR4 (X4 and CCR5 (R5-tropic HIV-1, was dose dependant and long lasting, did not inhibit cell growth or viability, was not toxic to cells, and was comparable to inhibition by the nucleoside analogue 2', 3'-didoxycytidine (ddC. S. fusiforme treatment blocked direct cell-to-cell infection spread. To investigate at which point of the virus life cycle this inhibition occurs, we infected T cells and CD4-negative primary human astrocytes with HIV-1 pseudotyped with envelope glycoprotein of vesicular stomatitis virus (VSV, which bypasses the HIV receptor requirements. Infection by pseudotyped HIV-1 (VSV/NL4-3 was also inhibited in a dose dependant manner, although up to 57% less, as compared to inhibition of native NL4-3, indicating post-entry interferences. Conclusion This is the first report demonstrating S. fusiforme to be a potent inhibitor of highly productive HIV-1 infection and replication in T cells, in primary human macrophages, microglia, and astrocytes. Results with VSV/NL4-3 infection, suggest inhibition

  17. EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

    Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

    2015-09-01

    Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased. PMID:26863859

  18. Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export

    Woods, Matthew William; Tong, Jessica Gayle; Tom, Sean Kevin; Szabo, Peter Anthony; Cavanagh, Peter Craig; Dikeakos, Jimmy Dimitrios; Haeryfar, SM Mansour; Barr, Stephen Dominic

    2014-01-01

    Background Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carbo...

  19. Oral complications of HIV disease

    Jair C. Leao

    2009-05-01

    Full Text Available Oral lesions are among the early signs of HIV infection and can predict its progression to acquired immunodeficiency syndrome (AIDS. A better understanding of the oral manifestations of AIDS in both adults and children has implications for all health care professionals. The knowledge of such alterations would allow for early recognition of HIV-infected patients. The present paper reviews epidemiology, relevant aspects of HIV infection related to the mouth in both adults and children, as well as current trends in antiretroviral therapy and its connection with orofacial manifestations related to AIDS.

  20. Self-assembly of block copolymers

    Hidenori Otsuka

    2001-05-01

    Full Text Available Block copolymers in a selective solvent have a tendency to self-assemble at surfaces and into micelles1–4. At an aqueous interface, the amphiphilic property of block copolymers composed of hydrophilic and hydrophobic segments can cause the distal end of the hydrophilic chain to extend into the bulk aqueous solution, anchoring the hydrophilic block to the substrate surface through hydrophobic segments1, 2. In an aqueous solution, micelles with core-shell structure are formed by the segregation of insoluble blocks into the core, which is surrounded by a hydrophilic shell composed of hydrophilic blocks3, 4. This interfacial activity of amphiphilic block copolymers provides their utility in the biomedical field as colloidal dispersants, surface modifiers and drug carriers, prompting many studies of block copolymer adsorption on solid surfaces5, 6, 7, 8, force measurements between tethered layers9, 10, 11 and the characterization of micelle properties12, 13, 14.