Science.gov

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

    SciTech Connect

    Hoque, M. Mominul; Suzuki, Kaoru; Tsunoda, Masaru; Jiang, Jiandong; Zhang, Fang; Takahashi, Atsushi; Ohbayashi, Naomi; Zhang, Xiaoxue; Tanaka, Haruo; Ōmura, Satoshi; Takénaka, Akio

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

    PubMed

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

    2012-08-01

    The essential step for HIV spreading limitation is the screening tests. However, there are multiple disadvantages in current screening assays which need further confirmation test. Herein we developed a rapid HIV assay combining screening and confirmation test by using the microfluidic network assay. Meanwhile, the assay is accelerated by bypassing the step of blocking. We call this method as microfluidic assay without blocking (MAWB). Both the limit of detection and reagent incubation time of MAWB are determined by screening of one model protein pair: ovalbumin and its antibody. The assay time is accelerated about 25% while the limit of detection (LOD) is well kept. Formatting the method in for both HIV screening (testing 8 HIV-related samples) and confirmation (assaying 6 kinds of HIV antibodies of each sample) within 30 min was successful. Fast HIV screening and confirmation of 20 plasma samples were also demonstrated by this method. MAWB improved the assay speed while keeping the LOD of conventional ELISA. Meanwhile, both the accuracy and throughput of MAWB were well improved, which made it an excellent candidate for a quick HIV test for both screening and confirmation. Methods like this one will find wide applications in clinical diagnosis and biochemical analysis based on the interactions between pairs of molecules. PMID:22374476

  3. Sulfonation Pathway Inhibitors Block Reactivation of Latent HIV-1

    PubMed Central

    Murry, Jeffrey P.; Godoy, Joseph; Mukim, Amey; Swann, Justine; Bruce, James W.; Ahlquist, Paul; Bosque, Alberto; Planelles, Vicente; Spina, Celsa A.; Young, John A. T.

    2015-01-01

    Long-lived pools of latently infected cells are a significant barrier to the development of a cure for HIV-1 infection. A better understanding of the mechanisms of reactivation from latency is needed to facilitate the development of novel therapies that address this problem. Here we show that chemical inhibitors of the sulfonation pathway prevent virus reactivation, both in latently infected J-Lat and U1 cell lines and in a primary human CD4+ T cell model of latency. In each of these models, sulfonation inhibitors decreased transcription initiation from the HIV-1 promoter. These inhibitors block transcription initiation at a step that lies downstream of nucleosome remodeling and affects RNA polymerase II recruitment to the viral promoter. These results suggest that the sulfonation pathway acts by a novel mechanism to regulate efficient virus transcription initiation during reactivation from latency, and further that augmentation of this pathway could be therapeutically useful. PMID:25310595

  4. Lectins with anti-HIV activity: a review.

    PubMed

    Akkouh, Ouafae; Ng, Tzi Bun; Singh, Senjam Sunil; Yin, Cuiming; Dan, Xiuli; Chan, Yau Sang; Pan, Wenliang; Cheung, Randy Chi Fai

    2015-01-01

    Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed. PMID:25569520

  5. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

    PubMed Central

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul

    2015-01-01

    ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1

  6. Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an Organ Culture

    PubMed Central

    Gupta, Phalguni; Ratner, Deena; Ding, Ming; Patterson, Bruce; Rohan, Lisa C; Reinhart, Todd A.; Ayyavoo, Velpandi; Huang, Xioli; Patton, Dorothy L; Ramratnam, Bharat; Cole, Alexander M

    2012-01-01

    Background Cervical tissue based organ cultures have been used successfully to evaluate microbicides for toxicity and antiviral activity. The antimicrobial peptide retrocyclin RC-101 has been shown to have potent anti-HIV activity in cell culture. Objective To evaluate RC-101 in organ culture for toxicity and its ability to block HIV-1 transmission across cervical mucosa. Methods A Cervical tissue based organ culture was used to measure antiviral activity of RC101. Cytotoxicity in tissues was determined by immunostaining of cellular proteins and by measuring inflammatory cytokines using realtime RTPCR and luminex technology. Results RC-101 blocked transmission of both R5 and X4 HIV-1 across cervical mucosa in this organ culture model. Furthermore, film-formulated RC-101 exhibited potent antiviral activity in organ culture. Such antiviral activity of RC-101 was retained in the presence of semen and vaginal fluid. RC-101 showed no cytotoxicity in cervical tissue. Furthermore, RC-101 did not induce proinflammatory cytokine response in tissues. RC-101 also did not have any effect on NK activity, cell proliferation of CD4 and CD8 cells, and did not show chemotactic activity. Conclusion Therefore, because of strong antiviral activity and low cytotoxicity in cervical tissues, RC-101 should be considered as an excellent microbicide candidate against HIV-1. PMID:22592582

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

    PubMed Central

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

    2015-01-01

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

  8. Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses

    PubMed Central

    Eid, Sahar G; Mangan, Niamh E; Hertzog, Paul J; Mak, Johnson

    2015-01-01

    The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract. PMID:26682051

  9. Blocking CXCL9 Decreases HIV-1 Replication and Enhances the Activity of Prophylactic Antiretrovirals in Human Cervical Tissues

    PubMed Central

    Macura, Sherrill L.; Lathrop, Melissa J.; Gui, Jiang; Doncel, Gustavo F.; Rollenhagen, Christiane

    2016-01-01

    Objectives: The interferon-gamma–induced chemokine CXCL9 is expressed in a wide range of inflammatory conditions including those affecting the female genital tract. CXCL9 promotes immune cell recruitment, activation, and proliferation. The role of CXCL9 in modulating HIV-1 infection of cervicovaginal tissues, a main portal of viral entry, however, has not been established. We report a link between CXCL9 and HIV-1 replication in human cervical tissues and propose CXCL9 as a potential target to enhance the anti–HIV-1 activity of prophylactic antiretrovirals. Design: Using ex vivo infection of human cervical tissues as a model of mucosal HIV-1 acquisition, we described the effect of CXCL9 neutralization on HIV-1 gene expression and mucosal CD4+ T-cell activation. The anti-HIV-1 activity of tenofovir, the leading mucosal pre-exposure prophylactic microbicide, alone or in combination with CXCL9 neutralization was also studied. Methods: HIV-1 replication was evaluated by p24 ELISA. HIV-1 DNA and RNA, and CD4, CCR5, and CD38 transcription were evaluated by quantitative real-time polymerase chain reaction. Frequency of activated cervical CD4+ T cells was quantified using fluorescence-activated cell sorting. Results: Antibody blocking of CXCL9 reduced HIV-1 replication by decreasing mucosal CD4+ T-cell activation. CXCL9 neutralization in combination with suboptimal concentrations of tenofovir, possibly present in the cervicovaginal tissues of women using the drug inconsistently, demonstrated an earlier and greater decrease in HIV-1 replication compared with tissues treated with tenofovir alone. Conclusions: CXCL9 neutralization reduces HIV-1 replication and may be an effective target to enhance the efficacy of prophylactic antiretrovirals. PMID:26545124

  10. Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication.

    PubMed

    Ali, Akbar; Ghosh, Animesh; Nathans, Robin S; Sharova, Natalia; O'Brien, Siobhan; Cao, Hong; Stevenson, Mario; Rana, Tariq M

    2009-08-17

    The positive transcription elongation factor (P-TEFb; CDK9/cyclin T1) regulates RNA polymerase II-dependent transcription of cellular and integrated viral genes. It is an essential cofactor for HIV-1 Tat transactivation, and selective inhibition of P-TEFb blocks HIV-1 replication without affecting cellular transcription; this indicates that P-TEFb could be a potential target for developing anti-HIV-1 therapeutics. Flavopiridol, a small molecule CDK inhibitor, blocks HIV-1 Tat transactivation and viral replication by inhibiting P-TEFb kinase activity, but it is highly cytotoxic. In the search for selective and less cytotoxic P-TEFb inhibitors, we prepared a series of flavopiridol analogues and evaluated their kinase inhibitory activity against P-TEFb and CDK2/cyclin A, and tested their cellular antiviral potency and cytotoxicity. We identified several analogues that selectively inhibit P-TEFb kinase activity in vitro and show antiviral potency comparable to that of flavopiridol, but with significantly reduced cytotoxicity. These compounds are valuable molecular probes for understanding P-TEFb-regulated cellular and HIV-1 gene transcription and provide potential anti-HIV-1 therapeutics. PMID:19603446

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

    PubMed

    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

  12. Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures

    PubMed Central

    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

    2014-01-01

    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

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

    SciTech Connect

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J.; Chen, Han; Zhou, You; Belshan, Michael

    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.

  14. GP41-specific Antibody Blocks Cell-free HIV-1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium#

    PubMed Central

    Shen, Ruizhong; Drelichman, Ernesto R.; Bimczok, Diane; Ochsenbauer, Christina; Kappes, John C.; Tudor, Daniela; Bomsel, Morgane; Smythies, Lesley E.; Smith, Phillip D.

    2013-01-01

    Monostratified epithelial cells translocate HIV-1 from the apical to the basolateral surface via vesicular transcytosis. Since acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral antibody blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r2 = 0.9846, P<0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05% and 1.21%, depending on the virus strain, producer cell type and gp120 V1-V3 loop signature. Inoculation of HIV-1 neutralizing antibodies to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 mAbs. Dimeric IgA (dIgA) and monomeric IgA (mIgA), but not polymeric IgM, 2F5 antibodies also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with mIgA substantially more potent than dIgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum. PMID:20208001

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

    PubMed Central

    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

  16. Blocking Type I Interferon Production: A New Therapeutic Option to Reduce the HIV-1-Induced Immune Activation

    PubMed Central

    Ries, Moritz; Pritschet, Kathrin; Schmidt, Barbara

    2012-01-01

    Highly active antiretroviral therapy has dramatically improved the morbidity and mortality of HIV-1-infected individuals. A total of 25 licensed drugs provide the basis for an optimized virus-suppressive treatment of nearly each subject. The promises of immune reconstitution and normal life expectancy, however, fall short for a number of patients, either through inadequate recovery of CD4+ T-cell counts or the occurrence of non-AIDS defining malignancies. In this respect, the prevalence of Epstein-Barr virus-associated Hodgkin lymphoma and human papillomavirus-related anal neoplasia is rising in aging HIV-1-infected individuals despite antiretroviral therapy. An important cause appears to be the HIV-1-induced chronic immune activation, propagated by inappropriate release of proinflammatory cytokines and type I interferons. This immune dysregulation can be reduced in vitro by inhibitors blocking the endosomal acidification. Recent data suggest that this concept is also of relevance in vivo, which opens the door for adjuvant immunomodulatory therapies in HIV-1 infection. PMID:22203858

  17. Extracurricular interest as a resilience building block for children affected by parental HIV/AIDS.

    PubMed

    Zhao, Junfeng; Chi, Peilian; Li, Xiaoming; Tam, Cheuk Chi; Zhao, Guoxiang

    2014-01-01

    Parental illness and death due to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) impose challenges to children's psychological adjustment. Positive psychology emphasizes individual's resilience in the face of adversity, trauma, and tragedy. Limited data are available regarding the factors that can cultivate resilience of children affected by HIV/AIDS. This study aims to examine the role of extracurricular interest in strengthening resilience among children affected by HIV/AIDS. Participants included 755 children orphaned by parental HIV/AIDS, 466 vulnerable children living with HIV-positive parent(s), and 404 comparison children from HIV-free families in the same community in rural China. The measures include extracurricular interest (i.e., reading, sports, music, painting, science, and playing chess) and indicators of psychological adjustment (i.e., depression, loneliness, and self-esteem). Having extracurricular interest was positively associated with self-esteem and negatively associated with depression and loneliness. Having extracurricular interest attenuated the negative effect of parental HIV/AIDS on children's self-esteem and loneliness, after controlling for children's age, gender, and family socioeconomic status. The findings underscore the importance of nurturing extracurricular interest and make available of such activities to promote resilience for children affected by HIV/AIDS in resource-limited settings. PMID:24107136

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

    PubMed Central

    Cinti, Alessandro; Le Sage, Valerie; Ghanem, Marwan

    2016-01-01

    ABSTRACT Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms. PMID:27025252

  19. Secretion Modification Region-Derived Peptide Disrupts HIV-1 Nef's Interaction with Mortalin and Blocks Virus and Nef Exosome Release

    PubMed Central

    Shelton, Martin N.; Huang, Ming-Bo; Ali, Syed A.; Powell, Michael D.

    2012-01-01

    Nef is secreted from infected cells in exosomes and is found in abundance in the sera of HIV-infected individuals. Secreted exosomal Nef (exNef) induces apoptosis in uninfected CD4+ T cells and may be a key component of HIV pathogenesis. The exosomal pathway has been implicated in HIV-1 virus release, suggesting a possible link between these two viral processes. However, the underlying mechanisms and cellular components of exNef secretion have not been elucidated. We have previously described a Nef motif, the secretion modification region (SMR; amino acids 66 to 70), that is required for exNef secretion. In silico modeling data suggest that this motif can form a putative binding pocket. We hypothesized that the Nef SMR binds a cellular protein involved in protein trafficking and that inhibition of this interaction would abrogate exNef secretion. By using tandem mass spectrometry and coimmunoprecipitation with a novel SMR-based peptide (SMRwt) that blocks exNef secretion and HIV-1 virus release, we identified mortalin as an SMR-specific cellular protein. A second set of coimmunoprecipitation experiments with full-length Nef confirmed that mortalin interacts with Nef via Nef's SMR motif and that this interaction is disrupted by the SMRwt peptide. Overexpression and microRNA knockdown of mortalin revealed a positive correlation between exNef secretion levels and mortalin protein expression. Using antibody inhibition we demonstrated that the Nef/mortalin interaction is necessary for exNef secretion. Taken together, this work constitutes a significant step in understanding the underlying mechanism of exNef secretion, identifies a novel host-pathogen interaction, and introduces an HIV-derived peptide with antiviral properties. PMID:22013042

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

    PubMed Central

    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 this class of inhibitors can suppress cell-to-cell transfer of HIV-1 is unexplored. Here we have evaluated the inhibitory effect of PIs during cell-to-cell spread of HIV-1 between T lymphocytes. Results Using quantitative assays in cell line and primary cell systems that directly measure the early steps of HIV-1 infection we find that the PIs Lopinavir and Darunavir are equally potent against both cell-free and cell-to-cell spread of HIV-1. We further show that a protease resistant mutant maintains its resistant phenotype during cell-to-cell spread and is transmitted more efficiently than wild-type virus in the presence of drug. By contrast we find that T cell-T cell spread of HIV-1 is 4–20 fold more resistant to inhibition by the RTIs Nevirapine, Zidovudine and Tenofovir. Notably, varying the ratio of infected and uninfected cells in co-culture impacted on the degree of inhibition, indicating that the relative efficacy of ART is dependent on the multiplicity of infection. Conclusions We conclude that if the variable effects of antiviral drugs on cell-to-cell virus dissemination of HIV-1 do indeed impact on viral replication and maintenance of viral reservoirs this is likely to be influenced by the antiviral drug class, since PIs appear particularly effective against both modes of HIV-1 spread. PMID:24364896

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

    PubMed Central

    Bashir, Tahir; Patgaonkar, Mandar; Kumar C, Selvaa; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

    2015-01-01

    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. PMID:25915507

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

    PubMed

    Bashir, Tahir; Patgaonkar, Mandar; Kumar, Selvaa C; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

    2015-01-01

    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. PMID:25915507

  3. The Nucleoside Analog D-carba T Blocks HIV-1 Reverse Transcription

    PubMed Central

    Boyer, Paul L.; Vu, B. Christie; Ambrose, Zandrea; Julias, John G.; Warnecke, Svenja; Liao, Chenzhong; Meier, Chris; Marquez, Victor E.; Hughes, Stephen H.

    2009-01-01

    A major pathway for HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTIs) involves reverse transcriptase (RT) mutations that enhance ATP-dependent pyrophosphorolysis, which excises NRTIs from the end of viral DNA. We analyzed novel NRTIs for their ability to inhibit DNA synthesis of excision-proficient HIV-1 RT mutants. D-carba T is a carbocyclic nucleoside that has a 3′ hydroxyl on the pseudosugar. The 3′ hydroxyl group allows RT to incorporate additional dNTPs, which should protect D-carba TMP from excision. D-carba T can be converted to the triphosphate form by host cell kinases with moderate efficiency. D-carba T-TP is efficiently incorporated by HIV-1 RT; however, the next dNTP is added slowly to a D-carba TMP at the primer terminus. D-carba T effectively inhibits viral vectors that replicate using NRTI-resistant HIV-1 RTs, and there is no obvious toxicity in cultured cells. NRTIs based on the carbocyclic pseudosugar may offer an effective approach for the treatment of HIV-1 infections. PMID:19678643

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

    PubMed

    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

  5. Non-Catalytic Site HIV-1 Integrase Inhibitors Disrupt Core Maturation and Induce a Reverse Transcription Block in Target Cells

    PubMed Central

    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

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

    SciTech Connect

    Federico, Maurizio

    2011-08-15

    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.

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

    PubMed

    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

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

    SciTech Connect

    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

    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.

  9. X-ray Structures of the Hexameric Building Block of the HIV Capsid

    PubMed Central

    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

    2010-01-01

    SUMMARY 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 forming 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. PMID:19523676

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

    PubMed Central

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J.; Chen, Han; Zhou, You; Belshan, Michael

    2014-01-01

    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 (MAΔ96-120) 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, MAΔ96-120 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. PMID:25217711

  11. Types of HIV/AIDS Antiretroviral Drugs

    MedlinePlus

    ... reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA―a process called ... RT, interfering with its ability to convert HIV RNA into HIV DNA Integrase Inhibitors block the HIV ...

  12. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells.

    PubMed Central

    Moore, J P; Sattentau, Q J; Klasse, P J; Burkly, L C

    1992-01-01

    The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion. Images PMID:1378510

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

    PubMed Central

    Gallay, Philippe A.; Bobardt, Michael D.; Chatterji, Udayan; Trepanier, Daniel J.; Ure, Daren; Ordonez, Cosme; Foster, Robert

    2015-01-01

    HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV-1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs), the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro “co-infection” model where HCV and HIV-1 concurrently replicate in their respective main host target cells—human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI), including a novel cyclosporin A (CsA) analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the “co-infection” system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI—alisporivir (ALV)—at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA) isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI-431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections. PMID:26263487

  14. Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG

    PubMed Central

    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; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Gilbert, Peter B.; Kim, Jerome H.; Michael, Nelson L.; Montefiori, David C.; Haynes, Barton F.

    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 hypothesis that IgA could attenuate the protective effect of IgG responses through competition for the same Env binding sites. We report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. Moreover, Env-specific IgA antibodies from RV144 vaccinees blocked the binding of ADCC-mediating mAb to HIV-1 Env glycoprotein 120 (gp120). An Env-specific monomeric IgA mAb isolated from an RV144 vaccinee also inhibited the ability of natural killer cells to kill HIV-1–infected CD4+ T cells coated with RV144-induced IgG antibodies. We show that monomeric Env-specific IgA, as part of postvaccination polyclonal antibody response, may modulate vaccine-induced immunity by diminishing ADCC effector function. PMID:23661056

  15. HIV

    PubMed Central

    Chawla, Sumit; Sahoo, Soumya Swaroop; Jain, Rambilas; Khanna, Pardeep; Mehta, Bharti; Singh, Inderjeet

    2014-01-01

    Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. PMID:24056755

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

    PubMed

    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

  17. Infection by HIV-1 blocked by binding of dextrin 2-sulphate to the cell surface of activated human peripheral blood mononuclear cells and cultured T-cells.

    PubMed Central

    Shaunak, S; Gooderham, N J; Edwards, R J; Payvandi, N; Javan, C M; Baggett, N; MacDermot, J; Weber, J N; Davies, D S

    1994-01-01

    1. Structural analogues of a sulphated polysaccharide, dextrin sulphate, were synthesized and tested for their ability to block infection by HIV-1. Using the T-cell lines, C8166 and HPB-ALL, and the laboratory adapted strains of HIV-1.MN, HIV-1.IIIb and HIV-1.RF, dextrin 2-sulphate (D2S) combined the best combination of high anti-HIV-1 activity (95% inhibitory concentration (IC95) = 230 nM) and low anticoagulant activity. It also blocked infection of activated peripheral blood mononuclear (PBMN) cells by five primary viral isolates at an IC95 of 230-3700 nM depending upon the primary viral isolate tested. 2. In saturation binding studies, [3H]-D2S bound to a cell surface protein on HPB-ALL cells in a specific and saturable manner with a Kd of 82 +/- 14 nM and a Bmax of 4.8 +/- 0.3 pmol/10(6) cells. It bound to other human T-cell lines in a similar manner. 3. There was very little binding of [3H]-D2S to freshly isolated PBMN cells (Bmax 0.18 +/- 0.03 pmol/10(6) cells) and these cells could not be infected by HIV-1. Culture of PBMN cells in lymphocyte growth medium (LGM) containing IL-2 did not significantly change the Bmax of [3H]-D2S. In contrast, PBMN cells which had been cultured with phytohaemagglutinin (PHA; 5 micrograms ml-1) for 72 h had a Bmax of [3H]-D2S binding of 7.2 +/- 0.1 pmol/10(6) cells and these cells could be infected by HIV-1. Removal of the PHA and further culture of the PBMN cells in LGM containing IL-2 resulted in a fall in the Bmax to 2.0 +/- 0.1 pmol/10(6) cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812605

  18. Monoclonal And Single Domain Antibodies Targeting β-Integrin Subunits Block Sexual Transmission of HIV-1 in in vitro and in vivo Model Systems

    PubMed Central

    Guedon, Janet Tai; Luo, Kun; Zhang, Hong; Markham, Richard B.

    2015-01-01

    Background Poor adherence to prevention regimens for gel-based anti-HIV-1 microbicides has been a major obstacle to more effective pre-exposure prophylaxis. Concern persists that the antiretroviral drug containing microbicides might promote development of antiretroviral resistance. Methods Using in vitro transwell systems and a humanized mouse model of HIV-1 sexual transmission, we examined, as candidate microbicides, antibodies targeting the heterodimeric leukocyte function associated antigen 1 (LFA-1), a non-virally encoded protein acquired by the virus that also plays a critical role cell movement across endothelial and epithelial barriers. LFA-1 specific single domain variable regions from alpaca heavy-chain only antibodies (VHH) were identified and evaluated for their ability to inhibit HIV-1 transmission in the in vitro transwell system. Results Monoclonal antibodies targeting the CD11a and CD18 components of LFA-1 significantly reduced cell-free and cell-associated HIV-1 transmission in the in vitro transwell culture system and prevented virus transmission in the humanized mouse model of vaginal transmission. The broadly neutralizing monoclonal antibody b12 was unable to block transmission of cell-free virus. CD11a-specific VHH were isolated and expressed and the purified variable region protein domains reduced in vitro transepithelial transmission with an efficacy comparable to that of the CD11a monoclonal antibody. Conclusions Targeting integrins acquired by HIV-1 during budding and which are critical to interactions between epithelial cells and lymphocytes can reduce viral movement across epithelial barriers and prevent transmission in a humanized mouse model of sexual transmission. VHH capable of being produced by transformed bacteria can significantly reduce transepithelial virus transmission in in vitro model systems. PMID:25828964

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

    PubMed

    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

  20. α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy.

    PubMed

    Lakritz, Jessica R; Thibault, Derek M; Robinson, Jake A; Campbell, Jennifer H; Miller, Andrew D; Williams, Kenneth C; Burdo, Tricia H

    2016-07-01

    Traffic of activated monocytes into the dorsal root ganglia (DRG) is critical for pathology in HIV peripheral neuropathy. We have shown that accumulation of recently recruited (bromodeoxyuridine(+) MAC387(+)) monocytes is associated with severe DRG pathology and loss of intraepidermal nerve fibers in SIV-infected macaques. Herein, we blocked leukocyte traffic by treating animals with natalizumab, which binds to α4-integrins. SIV-infected CD8-depleted macaques treated with natalizumab either early (the day of infection) or late (28 days after infection) were compared with untreated SIV-infected animals sacrificed at similar times. Histopathology showed diminished DRG pathology with natalizumab treatment, including decreased inflammation, neuronophagia, and Nageotte nodules. Natalizumab treatment resulted in a decrease in the number of bromodeoxyuridine(+) (early), MAC387(+) (late), CD68(+) (early and late), and SIVp28(+) (late) macrophages in DRG tissues. The number of CD3(+) T lymphocytes in DRGs was not affected by natalizumab treatment. Vascular cell adhesion molecule 1, an adhesion molecule that mediates leukocyte traffic, was diminished in DRGs of all natalizumab-treated animals. These data show that blocking monocyte, but not T lymphocyte, traffic to the DRG results in decreased inflammation and pathology, supporting a role for monocyte traffic and activation in HIV peripheral neuropathy. PMID:27157989

  1. Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... heart block. Doctors use a test called an EKG (electrocardiogram) to help diagnose heart block. This test ...

  2. FDA-Approved HIV Medicines

    MedlinePlus

    ... 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 ...

  3. Drugs That Fight HIV-1

    MedlinePlus

    ... 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, ...

  4. Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: Implications for HIV-1 susceptibility to channel blocking drugs

    PubMed Central

    Park, Sang Ho; Opella, Stanley J.

    2007-01-01

    The channel-forming trans-membrane domain of Vpu (Vpu TM) from HIV-1 is known to enhance virion release from the infected cells and is a potential target for ion-channel blockers. The substitution of alanine at position 18 by a histidine (A18H) has been shown to render HIV-1 infections susceptible to rimantadine, a channel blocker of M2 protein from the influenza virus. In order to describe the influence of the mutation on the structure and rimantadine susceptibility of Vpu, we determined the structure of A18H Vpu TM, and compared it to those of wild-type Vpu TM and M2 TM. Both isotropic and orientationally dependent NMR frequencies of the backbone amide resonance of His18 were perturbed by rimantadine, and those of Ile15 and Trp22 were also affected, suggesting that His18 is the key residue for rimantadine binding and that residues located on the same face of the TM helix are also involved. A18H Vpu TM has an ideal, straight α-helix spanning residues 6–27 with an average tilt angle of 41° in C14 phospholipid bicelles, indicating that the tilt angle is increased by 11° compared to that of wild-type Vpu TM. The longer helix formed by the A18H mutation has a larger tilt angle to compensate for the hydrophobic mismatch with the length of the phospholipids in the bilayer. These results demonstrate that the local change of the primary structure plays an important role in secondary and tertiary structures of Vpu TM in lipid bilayers and affects its ability to interact with channel blockers. PMID:17766368

  5. Population Blocks.

    ERIC Educational Resources Information Center

    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…

  6. HIV Symptoms

    MedlinePlus

    ... 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 ...

  7. Ionic Blocks

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; Gamble, Rex; Martinez, Elizabet; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    "Ionic Blocks" is a teaching tool designed to help middle school students visualize the concepts of ions, ionic compounds, and stoichiometry. It can also assist high school students in reviewing their subject mastery. Three dimensional blocks are used to represent cations and anions, with color indicating charge (positive or negative) and size…

  8. HIV Prevention

    MedlinePlus

    ... to treat HIV infection (called antiretroviral therapy, or ART) the right way, every day and his or ... way, every day, the medicine to treat HIV (ART) reduces the amount of HIV (called “viral ...

  9. Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay.

    PubMed Central

    Urabe, T; Sano, K; Nakano, T; Odawara, F; Lee, M H; Otake, T; Okubo, S; Hayami, M; Misaki, H; Baba, M

    1994-01-01

    We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay. Images PMID:7527425

  10. Advances in HIV Microbicide Development

    PubMed Central

    Olsen, Joanna S.; Easterhoff, David; Dewhurst, Stephen

    2014-01-01

    There is an urgent need for a way to control the spread of the global HIV pandemic. A microbicide, or topical drug applied to the mucosal environment to block transmission, is a promising HIV prevention strategy. The development of a safe and efficacious microbicide requires a thorough understanding of the mucosal environment and it's role in HIV transmission. Knowledge of the key events in viral infection identifies points at which the virus might be most effectively targeted by a microbicide. The cervicovaginal and rectal mucosa play an important role in the innate defense against HIV, and microbicides must not interfere with these functions. In this review we discuss the current research on HIV microbicide development. PMID:22098355

  11. Women and HIV

    MedlinePlus

    ... 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 ...

  12. TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core

    PubMed Central

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

    2012-01-01

    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 HIV-1 infection after nuclear import. PMID:22398280

  13. Get Tested for HIV

    MedlinePlus

    ... Print This Topic En español Get Tested for HIV Browse Sections The Basics Overview What Is HIV? ... 1 of 7 sections The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency ...

  14. HIV Treatment: The Basics

    MedlinePlus

    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- ...

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

    PubMed

    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

  16. HIV Transmission

    MedlinePlus

    ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ...

  17. 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

    PubMed Central

    Banks, Lauren B.; Iyer, Shilpa S.; Pfaff, Jennifer M.; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Decker, Julie M.; Parrish, Erica H.; Berg, Anna; Hopper, Jennifer; Hora, Bhavna; Kumar, Amit; Mahlokozera, Tatenda; Yuan, Sally; Coleman, Charl; Vermeulen, Marion; Ding, Haitao; Ochsenbauer, Christina; Tilton, John C.; Permar, Sallie R.; Kappes, John C.; Betts, Michael R.; Busch, Michael P.; Gao, Feng; Montefiori, David; Haynes, Barton F.; Shaw, George M.; Hahn, Beatrice H.; Doms, Robert W.

    2012-01-01

    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. PMID:22693444

  18. HIV Medication Adherence

    MedlinePlus

    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 ...

  19. HIV among Transgender People

    MedlinePlus

    ... of transgender Virginians . Richmond, VA: Virginia HIV Community Planning Committee and Virginia Department of Health; 2007. Accessed April 14, 2016. Additional ... HIV/AIDS CDC HIV CDC HIV/AIDS ...

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

    SciTech Connect

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    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.

  1. TIM-family proteins inhibit HIV-1 release

    PubMed Central

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

    2014-01-01

    Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV-1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors. PMID:25136083

  2. Types of Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... the P and the R waves on the EKG (electrocardiogram). First-degree heart block may not cause ...

  3. Screening and diagnosis for HIV

    MedlinePlus

    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 ...

  4. HIV among Women

    MedlinePlus

    ... testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS ... HIV infection—National HIV Behavioral Surveillance, 20 U.S. cities, 2013 . HIV Surveillance Special Report 13 . Accessed January ...

  5. Potentiation of the immune response in HIV-1+ individuals.

    PubMed

    Schmitz, T; Underwood, R; Khiroya, R; Bachovchin, W W; Huber, B T

    1996-03-15

    T cells from HIV-1+ individuals have a defect in mounting an antigen specific response. HIV-1 Tat has been implicated as the causative agent of this immunosuppression. We have previously shown that HIV-1 Tat inhibits antigen specific proliferation of normal T cells in vitro by binding to the accessory molecule CD26, a dipeptidase expressed on the surface of activated T cells. We now demonstrate that the defective in vitro recall antigen response in HIV-1 infected individuals can be restored by the addition of soluble CD26, probably by serving as a decoy receptor for HIV-1 Tat. The restored response is comparable to that of an HIV-1- individual, suggesting that early in HIV infection there is a block in the memory cell response, rather than deletion of these cells. PMID:8617888

  6. HIV / AIDS

    MedlinePlus

    ... Marketing Share this: Main Content Area Understanding HIV/AIDS AIDS was first reported in the United States in ... and has since become a major worldwide epidemic. AIDS is caused by the human immunodeficiency virus, or ...

  7. Kinase Control of Latent HIV-1 Infection: PIM-1 Kinase as a Major Contributor to HIV-1 Reactivation

    PubMed Central

    Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C.; Wagner, Frederic; Bosque, Alberto; Shishido, Takao; Jones, Jennifer; Planelles, Vicente; Willey, Christopher; Cron, Randall Q.

    2014-01-01

    Despite the clinical relevance of latent HIV-1 infection as a block to HIV-1 eradication, the molecular biology of HIV-1 latency remains incompletely understood. We recently demonstrated the presence of a gatekeeper kinase function that controls latent HIV-1 infection. Using kinase array analysis, we here expand on this finding and demonstrate that the kinase activity profile of latently HIV-1-infected T cells is altered relative to that of uninfected T cells. A ranking of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key switch involved in HIV-1 latency control. Using genetic and pharmacologic perturbation strategies, we demonstrate that PIM-1 activity is indeed required for HIV-1 reactivation in T cell lines and primary CD4 T cells. The presented results thus confirm that kinases are key contributors to HIV-1 latency control. In addition, through mutational studies we link the inhibitory effect of PIM-1 inhibitor IV (PIMi IV) on HIV-1 reactivation to an AP-1 motif in the CD28-responsive element of the HIV-1 long terminal repeat (LTR). The results expand our conceptual understanding of the dynamic interactions of the host cell and the latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel molecular mechanisms that can eventually be targeted to therapeutically trigger HIV-1 reactivation. PMID:24155393

  8. Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation.

    PubMed

    Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C; Wagner, Frederic; Bosque, Alberto; Shishido, Takao; Jones, Jennifer; Planelles, Vicente; Willey, Christopher; Cron, Randall Q; Kutsch, Olaf

    2014-01-01

    Despite the clinical relevance of latent HIV-1 infection as a block to HIV-1 eradication, the molecular biology of HIV-1 latency remains incompletely understood. We recently demonstrated the presence of a gatekeeper kinase function that controls latent HIV-1 infection. Using kinase array analysis, we here expand on this finding and demonstrate that the kinase activity profile of latently HIV-1-infected T cells is altered relative to that of uninfected T cells. A ranking of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key switch involved in HIV-1 latency control. Using genetic and pharmacologic perturbation strategies, we demonstrate that PIM-1 activity is indeed required for HIV-1 reactivation in T cell lines and primary CD4 T cells. The presented results thus confirm that kinases are key contributors to HIV-1 latency control. In addition, through mutational studies we link the inhibitory effect of PIM-1 inhibitor IV (PIMi IV) on HIV-1 reactivation to an AP-1 motif in the CD28-responsive element of the HIV-1 long terminal repeat (LTR). The results expand our conceptual understanding of the dynamic interactions of the host cell and the latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel molecular mechanisms that can eventually be targeted to therapeutically trigger HIV-1 reactivation. PMID:24155393

  9. Testing block subdivision algorithms on block designs

    NASA Astrophysics Data System (ADS)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

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

    NASA Astrophysics Data System (ADS)

    Jiang, Shibo; Radigan, Lin; Zhang, Li

    2000-03-01

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

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

    SciTech Connect

    Armand-Ugon, Mercedes; Clotet-Codina, Imma; Tintori, Cristina; Manetti, Fabrizio; Clotet, Bonaventura; Botta, Maurizio; Este, Jose A. . E-mail: jaeste@irsicaixa.es

    2005-12-05

    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.

  12. Geography Should Not Be Destiny: Focusing HIV/AIDS Implementation Research and Programs on Microepidemics in US Neighborhoods

    PubMed Central

    Yolken, Annajane; Cutler, Blayne; Trooskin, Stacey; Wilson, Phill; Little, Susan; Mayer, Kenneth

    2014-01-01

    African Americans and Hispanics are disproportionately affected by the HIV/AIDS epidemic. Within the most heavily affected cities, a few neighborhoods account for a large share of new HIV infections. Addressing racial and economic disparities in HIV infection requires an implementation program and research agenda that assess the impact of HIV prevention interventions focused on increasing HIV testing, treatment, and retention in care in the most heavily affected neighborhoods in urban areas of the United States. Neighborhood-based implementation research should evaluate programs that focus on community mobilization, media campaigns, routine testing, linkage to and retention in care, and block-by-block outreach strategies. PMID:24716570

  13. HIV Life Cycle

    MedlinePlus

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

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

    PubMed

    Chaves Valadão, Ana Luiza; Abreu, Celina Monteiro; Dias, Juliana Zanatta; Arantes, Pablo; Verli, Hugo; Tanuri, Amilcar; de Aguiar, Renato Santana

    2015-01-01

    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. PMID:26111177

  15. Neutralizing antibodies to HIV-1 induced by immunization

    PubMed Central

    McCoy, Laura E.

    2013-01-01

    Most neutralizing antibodies act at the earliest steps of viral infection and block interaction of the virus with cellular receptors to prevent entry into host cells. The inability to induce neutralizing antibodies to HIV has been a major obstacle to HIV vaccine research since the early days of the epidemic. However, in the past three years, the definition of a neutralizing antibody against HIV has been revolutionized by the isolation of extremely broad and potent neutralizing antibodies from HIV-infected individuals. Considerable hurdles remain for inducing neutralizing antibodies to a protective level after immunization. Meanwhile, novel technologies to bypass the induction of antibodies are being explored to provide prophylactic antibody-based interventions. This review addresses the challenge of inducing HIV neutralizing antibodies upon immunization and considers notable recent advances in the field. A greater understanding of the successes and failures for inducing a neutralizing response upon immunization is required to accelerate the development of an effective HIV vaccine. PMID:23401570

  16. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells.

    PubMed Central

    Mayaux, J F; Bousseau, A; Pauwels, R; Huet, T; Hénin, Y; Dereu, N; Evers, M; Soler, F; Poujade, C; De Clercq, E

    1994-01-01

    A series of triterpene compounds characterized by a stringent structure-activity relationship were identified as potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. Currently studied botulinic derivatives have 50% inhibitory concentrations (IC50) against HIV-1 strain IIIB/LAI in the 10 nM range in several cellular infection assays but are inactive against HIV-2. These compounds did not significantly inhibit the in vitro activities of several purified HIV-1 enzymes. Rather, they appeared to block virus infection at a postbinding, envelope-dependent step involved in the fusion of the virus to the cell membrane. PMID:8170948

  17. Block That Pain!

    MedlinePlus

    ... combination produces a unique effect, blocking pain-sensing neurons without impairing signals from other cells. In contrast, ... surgical procedures block activity in all types of neurons. This can cause numbness, paralysis, and other nervous ...

  18. The Block Scheduling Handbook.

    ERIC Educational Resources Information Center

    Queen, J. Allen

    Block scheduling encourages increased comprehensive immersion into subject matter, improved teacher-student relationships, and decreased disciplinary problems. While block scheduling may offer many advantages, moving to a block schedule from conventional scheduling can be a major adjustment for both students and teachers. This guide is intended to…

  19. Block Scheduling. Research Brief

    ERIC Educational Resources Information Center

    Muir, Mike

    2003-01-01

    What are the effects of block scheduling? Results of transitioning from traditional to block scheduling are mixed. Some studies indicate no change in achievement results, nor change in teachers' opinions about instructional strategies. Other studies show that block scheduling doesn't work well for Advanced Placement or Music courses, that "hard to…

  20. HIV Testing

    MedlinePlus

    ... the right way, every day. If you have health insurance, your insurer is required to cover some medicines ... to treat HIV. If you don’t have health insurance, or you’re unable to afford your co- ...

  1. HIV/AIDS

    MedlinePlus

    ... at risk for serious infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most often spreads through unprotected sex with ...

  2. Preventing HIV with Medicine

    MedlinePlus

    ... information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

  3. HIV/AIDS

    MedlinePlus

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

  4. How HIV Causes AIDS

    MedlinePlus

    ... 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 ...

  5. HIV/AIDS Basics

    MedlinePlus

    ... Enter ZIP code or city Follow Act Against AIDS Act Against AIDS @talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

  6. HIV-AIDS Connection

    MedlinePlus

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

  7. HIV/AIDS

    MedlinePlus

    ... HIV infections. HIV infection is often diagnosed through rapid diagnostic tests (RDTs), which detect the presence or absence of ... accuracy. It is important to note that serological tests detect antibodies produced ... pathogens, rather than direct detection of HIV itself. Most ...

  8. Older People and HIV

    MedlinePlus

    ... common than they were before the use of anti-HIV drugs. It is difficult to know what is causing mental problems in older people with HIV. Is it normal aging, or is it HIV disease? Research studies have ...

  9. Blocking Delaunay triangulations

    PubMed Central

    Aichholzer, Oswin; Fabila-Monroy, Ruy; Hackl, Thomas; van Kreveld, Marc; Pilz, Alexander; Ramos, Pedro; Vogtenhuber, Birgit

    2013-01-01

    Given a set B of n black points in general position, we say that a set of white points W blocks B if in the Delaunay triangulation of B∪W there is no edge connecting two black points. We give the following bounds for the size of the smallest set W blocking B: (i) 3n/2 white points are always sufficient to block a set of n black points, (ii) if B is in convex position, 5n/4 white points are always sufficient to block it, and (iii) at least n−1 white points are always necessary to block a set of n black points. PMID:23483043

  10. Blocking Delaunay triangulations.

    PubMed

    Aichholzer, Oswin; Fabila-Monroy, Ruy; Hackl, Thomas; van Kreveld, Marc; Pilz, Alexander; Ramos, Pedro; Vogtenhuber, Birgit

    2013-02-01

    Given a set B of n black points in general position, we say that a set of white points W blocks B if in the Delaunay triangulation of [Formula: see text] there is no edge connecting two black points. We give the following bounds for the size of the smallest set W blocking B: (i) [Formula: see text] white points are always sufficient to block a set of n black points, (ii) if B is in convex position, [Formula: see text] white points are always sufficient to block it, and (iii) at least [Formula: see text] white points are always necessary to block a set of n black points. PMID:23483043

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

    PubMed Central

    Posch, Wilfried; Steger, Marion; Knackmuss, Ulla; Blatzer, Michael; Baldauf, Hanna-Mari; Doppler, Wolfgang; White, Tommy E.; Hörtnagl, Paul; Diaz-Griffero, Felipe; Lass-Flörl, Cornelia; Hackl, Hubert; Moris, Arnaud; Keppler, Oliver T.; Wilflingseder, Doris

    2015-01-01

    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. PMID:26121641

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

    PubMed

    Posch, Wilfried; Steger, Marion; Knackmuss, Ulla; Blatzer, Michael; Baldauf, Hanna-Mari; Doppler, Wolfgang; White, Tommy E; Hörtnagl, Paul; Diaz-Griffero, Felipe; Lass-Flörl, Cornelia; Hackl, Hubert; Moris, Arnaud; Keppler, Oliver T; Wilflingseder, Doris

    2015-06-01

    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. PMID:26121641

  13. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

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

    PubMed

    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

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

    PubMed Central

    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

  16. HIV-1 propagates in human neuroblastoma cells.

    PubMed

    Shapshak, P; Sun, N C; Resnick, L; Thornthwaite, J T; Schiller, P; Yoshioka, M; Svenningsson, A; Tourtellotte, W W; Imagawa, D T

    1991-01-01

    A major question in the pathogenesis of AIDS encephalopathy and dementia is whether HIV-1 directly infects cells of the central nervous system (CNS). The propagation of HIV was attempted in six cell lines: three related and three unrelated to the nervous system. HIV was able to propagate in two human neuroblastoma cell lines and a lymphocytic cell line control but did not result in infections of African green monkey kidney cells, human cervix carcinoma cells, and one human brain astrocytoma cell line. Neuroblastoma cell lines infected with HIV showed peaks of reverse transcriptase activity at 10-14 days postinfection. After prolonged growth in cell cultures, one of the neuroblastoma cell lines showed multiphasic virus production, additional high peaks of reverse transcriptase activity, 20-fold greater than the first, lasting from 36 to 74 days and 110 to 140 days postinfection. The presence of HIV was confirmed by p24 antigen capture. The neuroblastoma cell lines had weak but detectable levels of CD4 immunoreactivity by immunoperoxidase and flow immunocytometric analysis. Although no T4-specific RNA sequences were detected by hybridization of Northern blots of total and poly A-selected RNA extracted from the two neuroblastoma cell lines by using a T4 specific complimentary DNA probe, monoclonal antibodies to the CD4 receptor blocked HIV infection in both neuroblastoma cell lines. Thus, the infection of neuroblastoma cells by HIV occurs in part by a CD4-dependent mechanism. Passaging the neuroblastoma cell lines weekly and bimonthly resulted in similar cell cycle-DNA content patterns for the more permissive cell line and with significant numbers of cells in the S phase. HIV-infected neuroblastoma cell lines provide an in vitro model for the evaluation of virus-host cell interactions and may be useful in addressing the issue of the persistence of HIV in the human CNS. PMID:1704060

  17. Blocked randomization with randomly selected block sizes.

    PubMed

    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

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

    PubMed

    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

  19. Protein based Block Copolymers

    PubMed Central

    Rabotyagova, Olena S.; Cebe, Peggy; Kaplan, David L.

    2011-01-01

    Advances in genetic engineering have led to the synthesis of protein-based block copolymers with control of chemistry and molecular weight, resulting in unique physical and biological properties. The benefits from incorporating peptide blocks into copolymer designs arise from the fundamental properties of proteins to adopt ordered conformations and to undergo self-assembly, providing control over structure formation at various length scales when compared to conventional block copolymers. This review covers the synthesis, structure, assembly, properties, and applications of protein-based block copolymers. PMID:21235251

  20. HIV and AIDS

    MedlinePlus

    ... I Help a Friend Who Cuts? HIV and AIDS KidsHealth > For Teens > HIV and AIDS Print A A A Text Size What's in ... in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type ...

  1. HIV Structural Database

    National Institute of Standards and Technology Data Gateway

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

  2. The hunt for HIV-1 integrase inhibitors.

    PubMed

    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

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

    PubMed Central

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

    2008-01-01

    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. PMID:18197976

  4. Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication.

    PubMed Central

    Romero, D L; Busso, M; Tan, C K; Reusser, F; Palmer, J R; Poppe, S M; Aristoff, P A; Downey, K M; So, A G; Resnick, L

    1991-01-01

    Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection. Images PMID:1717988

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

    MedlinePlus

    ... medlineplus/news/fullstory_158039.html Doctors Report Groundbreaking HIV-to-HIV Organ Transplants One donor supplied a kidney to ... News) -- Trailblazing liver and kidney transplants from an HIV-positive donor to HIV-positive recipients were announced ...

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

    MedlinePlus

    ... 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 ...

  7. High Relief Block Printing.

    ERIC Educational Resources Information Center

    Foster, Michael

    1989-01-01

    Explains a method of block printing using styrofoam shapes to make high relief. Describes the creation of the block design as well as the actual printing process. Uses a range of paper types for printing so children can see the results of using different media. (LS)

  8. Surviving Block Scheduling.

    ERIC Educational Resources Information Center

    Haley, Marjorie

    A discussion of block scheduling for second language instruction looks at the advantages and disadvantages and offers some suggestions for classroom management and course organization. It is argued that block scheduling may offer a potential solution to large classes, insufficient time for labs, too little individualized instruction; few…

  9. Block Scheduling Revisited.

    ERIC Educational Resources Information Center

    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…

  10. Thermally actuated wedge block

    DOEpatents

    Queen, Jr., Charles C.

    1980-01-01

    This invention relates to an automatically-operating wedge block for maintaining intimate structural contact over wide temperature ranges, including cryogenic use. The wedging action depends on the relative thermal expansion of two materials having very different coefficients of thermal expansion. The wedge block expands in thickness when cooled to cryogenic temperatures and contracts in thickness when returned to room temperature.

  11. A cell-intrinsic inhibitor of HIV-1 reverse transcription in CD4(+) T cells from elite controllers.

    PubMed

    Leng, Jin; Ho, Hsin-Pin; Buzon, Maria J; Pereyra, Florencia; Walker, Bruce D; Yu, Xu G; Chang, Emmanuel J; Lichterfeld, Mathias

    2014-06-11

    HIV-1 reverse transcription represents the predominant target for pharmacological inhibition of viral replication, but cell-intrinsic mechanisms that can block HIV-1 reverse transcription in a clinically significant way are poorly defined. We find that effective HIV-1 reverse transcription depends on the phosphorylation of viral reverse transcriptase by host cyclin-dependent kinase (CDK) 2 at a highly conserved Threonine residue. CDK2-dependent phosphorylation increased the efficacy and stability of viral reverse transcriptase and enhanced viral fitness. Interestingly, p21, a cell-intrinsic CDK inhibitor that is upregulated in CD4(+) T cells from "elite controllers," potently inhibited CDK2-dependent phosphorylation of HIV-1 reverse transcriptase and significantly reduced the efficacy of viral reverse transcription. These data suggest that p21 can indirectly block HIV-1 reverse transcription by inhibiting host cofactors supporting HIV-1 replication and identify sites of viral vulnerability that are effectively targeted in persons with natural control of HIV-1 replication. PMID:24922574

  12. HIV binding, penetration, and primary infection in human cervicovaginal tissue

    PubMed Central

    Maher, Diane; Wu, Xiaoyun; Schacker, Timothy; Horbul, Julie; Southern, Peter

    2005-01-01

    We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3–4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against β1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract. PMID:16061810

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

    ERIC Educational Resources Information Center

    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…

  14. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    PubMed Central

    Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

    2015-01-01

    HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

  15. Cell block eleven (left) and cell block fifteen, looking from ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Cell block eleven (left) and cell block fifteen, looking from cell block two into the "Death Row" exercise yard - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  16. View of cell block eight (left), cell block seven, and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of cell block eight (left), cell block seven, and southwest guard tower, looking from cell block eight roof - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  17. Blocked tear duct

    MedlinePlus

    ... your baby may have an eye infection called conjunctivitis . ... increase the chance of other infections, such as conjunctivitis. ... be prevented. Proper treatment of nasal infections and conjunctivitis may reduce the risk of having a blocked ...

  18. RX for Writer's Block.

    ERIC Educational Resources Information Center

    Tompkins, Gail E.; Camp, Donna J.

    1988-01-01

    Describes four prewriting techniques that elementary and middle grade students can use to gather and organize ideas for writing, and by so doing, cure writer's block. Techniques discussed are: (1) brainstorming; (2) clustering; (3) freewriting; and (4) cubing.

  19. Superalloy Lattice Block Structures

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  20. Block copolymer battery separator

    DOEpatents

    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.

  1. Reliable Genotypic Tropism Tests for the Major HIV-1 Subtypes

    PubMed Central

    Cashin, Kieran; Gray, Lachlan R.; Harvey, Katherine L.; Perez-Bercoff, Danielle; Lee, Guinevere Q.; Sterjovski, Jasminka; Roche, Michael; Demarest, James F.; Drummond, Fraser; Harrigan, P. Richard; Churchill, Melissa J.; Gorry, Paul R.

    2015-01-01

    Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic “tropism tests” to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic. PMID:25712827

  2. Enhanced HIV-1 neutralization by antibody heteroligation

    PubMed Central

    Mouquet, Hugo; Warncke, Malte; Scheid, Johannes F.; Seaman, Michael S.; Nussenzweig, Michel C.

    2012-01-01

    Passive transfer of broadly neutralizing human antibodies against HIV-1 protects macaques against infection. However, HIV-1 uses several strategies to escape antibody neutralization, including mutation of the gp160 viral surface spike, a glycan shield to block antibody access to the spike, and expression of a limited number of viral surface spikes, which interferes with bivalent antibody binding. The latter is thought to decrease antibody apparent affinity or avidity, thereby interfering with neutralizing activity. To test the idea that increasing apparent affinity might enhance neutralizing activity, we engineered bispecific anti–HIV-1 antibodies (BiAbs) that can bind bivalently by virtue of one scFv arm that binds to gp120 and a second arm to the gp41 subunit of gp160. The individual arms of the BiAbs preserved the binding specificities of the original anti-HIV IgG antibodies and together bound simultaneously to gp120 and gp41. Heterotypic bivalent binding enhanced neutralization compared with the parental antibodies. We conclude that antibody recognition and viral neutralization of HIV can be improved by heteroligation. PMID:22219363

  3. Testing for HIV

    MedlinePlus

    ... 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. HIV/AIDS

    MedlinePlus

    ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ... cancers. When that happens, the illness is called AIDS. Once a person has the virus, it stays ...

  5. HIV and AIDS

    MedlinePlus

    ... that causes the disease AIDS. HIV Hurts the Immune System People who are HIV positive have been tested ... to everyone in the world. When the person's immune system has weakened and more of the blood's T ...

  6. Microbiome in HIV infection

    PubMed Central

    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 inflammation are associated with increased risks of HIV acquisition, suggesting the role of microbiome in HIV transmission. In this review, we will focus on microbiome in HIV infection at various mucosal compartments. Understanding the relationship between microbiome and HIV may offer insights into development of better strategies for HIV prevention and treatment. PMID:25439273

  7. HIV and Cardiovascular Disease

    MedlinePlus

    ... CVD. ART can increase blood fats (cholesterol and triglycerides, see fact sheet 123.) It can also help ... disease. HIV infection decreases good cholesterol and increases triglycerides. HIV causes inflammation. This can also contribute to ...

  8. Older People and HIV

    MedlinePlus

    ... Many older people believe that HIV only affects younger people Most older people get little training in ... diseases among older people, as they do for younger people. Physicians may not diagnose HIV infection in ...

  9. Smoking and HIV

    MedlinePlus

    ... 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 ...

  10. HIV and Pregnancy

    MedlinePlus

    ... Pregnancy Patient Education FAQs HIV and Pregnancy Patient Education Pamphlets - Spanish HIV and Pregnancy FAQ113, December 2012 PDF Format ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  11. Immunogenetics of HIV and HIV associated tuberculosis.

    PubMed

    Raghavan, S; Alagarasu, K; Selvaraj, P

    2012-01-01

    Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected patients, and is the leading cause of mortality among HIV-infected patients. Genetic susceptibility to TB in HIV negative subjects is well documented. Since coinfections can influence the way in which immune system respond to different pathogens, genetic susceptibility to TB in HIV patients might also change. Studies from India and other parts of the world have shown that genetic susceptibility to TB is influenced by HIV infection. In the present review, we emphasize the role of genetic factors in determining susceptibility to HIV infection, disease progression and development of TB in HIV-infected patients. Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients. However, the results are inconclusive and larger well-defined studies with precise clinical data are required to validate these associations. Apart from candidate gene approach, genome-wide association studies are also needed to unravel the unknown or to establish the previously reported genetic associations with HIV associated TB. Despite the preliminary status of the reported associations, it is becoming clear that susceptibility to development of TB in HIV patients is influenced by both environmental and genetic components. Understanding the genetic and immunologic factors that influence susceptibility to TB in HIV patients could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease. PMID:21943869

  12. Reduce HIV Risk

    MedlinePlus

    ... are increasing among younger people from 13 to 30 years of age. The key to defeating HIV lies ... Control and Prevention (CDC) has used them as models, and Dr. Jemmott was invited to South Africa to help decrease HIV/AIDS there. "For the past 15 years, I have observed how the HIV/AIDS epidemic ...

  13. HIV and the menopause.

    PubMed

    Fan, Maria D; Maslow, Bat-Sheva; Santoro, Nanette; Schoenbaum, Ellie

    2008-12-01

    Dramatic improvement in the survival of the HIV population has occurred with the ascendance of highly active antiretroviral therapy (HAART). In the foreseeable future, HIV-infected women who acquired disease during the peak years of the epidemic are expected to survive to experience menopause and even years beyond. The HIV epidemic may be viewed as 'mature', as its earlier victims become part of the geriatric population. Research about the process of menopause in HIV-infected women and, conversely, about HIV infection in women undergoing menopause is currently limited. Existing research suggests that the process of menopause is affected by HIV infection, inasmuch as infected women appear to experience menopause at an earlier age, with greater symptomatology, and with different reproductive hormone profiles compared with HIV-uninfected women. HIV infection also appears to affect bone mineral density, cardiovascular disease and cognition, with some age-related interactions. Lifestyle and demographic factors have pervasive importance for both HIV infection and the menopause in women. This article reviews the current state of knowledge about the menopausal process in HIV-infected women, and the common conditions in postmenopausal women that are likely to be affected by HIV infection. Clinicians should appreciate the potential role of HIV infection in caring for menopause-aged women. PMID:19037065

  14. HIV Disease: Current Concepts.

    ERIC Educational Resources Information Center

    Keeling, Richard P.

    1993-01-01

    Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…

  15. Impression block with orientator

    NASA Astrophysics Data System (ADS)

    Brilin, V. I.; Ulyanova, O. S.

    2015-02-01

    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.

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

    PubMed

    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

  17. Bactericidal block copolymer micelles.

    PubMed

    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

  18. Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2

    PubMed Central

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

    2016-01-01

    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

  19. Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2.

    PubMed

    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

  20. A Place for Block Play.

    ERIC Educational Resources Information Center

    Moore, Gary T.

    1997-01-01

    Discusses the importance of block play--including its contributions to perceptual, fine motor, and cognitive development--and components of a good preschool block play area. Recommends unit blocks complemented by stacking blocks, toys, beads, cubes, and Brio wooden toys. Makes recommendations for space, size, locations and connections to other…

  1. Tuberculosis and HIV Coinfection.

    PubMed

    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

  2. Basic HIV/AIDS Statistics

    MedlinePlus

    ... 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 | ... Collapse All How many people are diagnosed with HIV each year in the United States? In 2014, ...

  3. HIV Medicines and Side Effects

    MedlinePlus

    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 ...

  4. 2000 CENSUS BLOCK BOUNDARIES

    EPA Science Inventory

    This data set is a polygon shapefile of the boundaries of Census Blocks in New England derived from U.S. Census Bureau 2000 TIGER/Line data. Numerous attributes pertaining to population are included. TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau o...

  5. Confinement of block copolymers

    SciTech Connect

    1995-12-31

    The following were studied: confinement of block copolymers, free surface confinement, effects of substrate interactions, random copolymers at homopolymer interfaces, phase separation in thin film polymer mixtures, buffing of polymer surfaces, and near edge x-ray absorption fine structure spectroscopy.

  6. A Fluid Block Schedule

    ERIC Educational Resources Information Center

    Ubben, Gerald C.

    1976-01-01

    Achieving flexibility without losing student accountability is a challenge that faces every school. With a fluid block schedule, as described here, accountability is maintained without inhibiting flexibility. An additional advantage is that three levels of schedule decision making take some of the pressure off the principal. (Editor)

  7. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  8. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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

  10. Antiviral activity of CYC202 in HIV-1-infected cells.

    PubMed

    Agbottah, Emmanuel; de La Fuente, Cynthia; Nekhai, Sergie; Barnett, Anna; Gianella-Borradori, Athos; Pumfery, Anne; Kashanchi, Fatah

    2005-01-28

    There are currently 40 million individuals in the world infected with human immunodeficiency virus (HIV). The introduction of highly active antiretroviral therapy (HAART) has led to a significant reduction in AIDS-related morbidity and mortality. Unfortunately, up to 25% of patients discontinue their initial HAART regimen. Current HIV-1 inhibitors target the fusion of the virus to the cell and two viral proteins, reverse transcriptase and protease. Here, we examined whether other targets, such as an activated transcription factor, could be targeted to block HIV-1 replication. We specifically asked whether we could target a cellular kinase needed for HIV-1 transcription using CYC202 (R-roscovitine), a pharmacological cyclin-dependent kinase inhibitor. We targeted the cdk2-cyclin E complex in HIV-1-infected cells because both cdk2 and cyclin E are nonessential during mammalian development and are likely replaced by other kinases. We found that CYC202 effectively inhibits wild type and resistant HIV-1 mutants in T-cells, monocytes, and peripheral blood mononuclear cells at a low IC(50) and sensitizes these cells to enhanced apoptosis resulting in a dramatic drop in viral titers. Interestingly, the effect of CYC202 is independent of cell cycle stage and more specific for the cdk2-cyclin E complex. Finally, we show that cdk2-cyclin E is loaded onto the HIV-1 genome in vivo and that CYC202 is able to inhibit the uploading of this cdk-cyclin complex onto HIV-1 DNA. Therefore, targeting cellular enzymes necessary for HIV-1 transcription, which are not needed for cell survival, is a compelling strategy to inhibit wild type and mutant HIV-1 strains. PMID:15531588

  11. [Masquerading bundle branch block].

    PubMed

    Kukla, Piotr; Baranchuk, Adrian; Jastrzębski, Marek; Bryniarski, Leszek

    2014-01-01

    We here describe a surface 12-lead electrocardiogram (ECG) of a 72-year-old female with a prior history of breast cancer and chemotherapy-induced cardiomyopathy. An echocardiogram revealed left ventricular dysfunction, ejection fraction of 23%, with mild enlarged left ventricle. The 12-lead ECG showed atrial fibrillation with a mean heart rate of about 100 bpm, QRS duration 160 ms, QT interval 400 ms, right bundle branch block (RBBB) and left anterior fascicular block (LAFB). The combination of RBBB features in the precordial leads and LAFB features in the limb leads is known as ''masquerading bundle branch block''. In most cases of RBBB and LAFB, the QRS axis deviation is located between - 80 to -120 degrees. Rarely, when predominant left ventricular forces are present, the QRS axis deviation is near about -90 degrees, turning the pattern into an atypical form. In a situation of RBBB associated with LAFB, the S wave can be absent or very small in lead I. Such a situation is the result of not only purely LAFB but also with left ventricular hypertrophy and/or focal block due to scar (extensive anterior myocardial infarction) or fibrosis (cardiomyopathy). Sometimes, this specific ECG pattern is mistaken for LBBB. RBBB with LAFB may imitate LBBB either in the limb leads (known as 'standard masquerading' - absence of S wave in lead I), or in the precordial leads (called 'precordial masquerading' - absence of S wave in leads V₅ and V₆). Our ECG showed both these types of masquerading bundle branch block - absence of S wave in lead I and in leads V₅ and V₆. PMID:24469750

  12. Probing Multidrug-Resistance and Protein-Ligand Interactions with Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors

    SciTech Connect

    Ghosh, Arun K.; Xu, Chun-Xiao; Rao, Kalapala V.; Baldridge, Abigail; Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.; Aoki, Manabu; Miguel, Salcedo Pedro; Amano, Masayuki; Mitsuya, Hiroaki

    2010-10-29

    We report the design, synthesis, biological evaluation, and X-ray crystallographic analysis of a new class of HIV-1 protease inhibitors. Compound 4 proved to be an extremely potent inhibitor toward various multidrug-resistant HIV-1 variants, representing a near 10-fold improvement over darunavir (DRV). Compound 4 also blocked protease dimerization with at least 10-fold greater potency than DRV.

  13. Side Effects of HIV Medicines: HIV and Osteoporosis

    MedlinePlus

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

  14. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  15. Topical application of entry inhibitors as "virustats" to prevent sexual transmission of HIV infection

    PubMed Central

    Lederman, Michael M; Jump, Robin; Pilch-Cooper, Heather A; Root, Michael; Sieg, Scott F

    2008-01-01

    With the continuing march of the AIDS epidemic and little hope for an effective vaccine in the near future, work to develop a topical strategy to prevent HIV infection is increasingly important. This stated, the track record of large scale "microbicide" trials has been disappointing with nonspecific inhibitors either failing to protect women from infection or even increasing HIV acquisition. Newer strategies that target directly the elements needed for viral entry into cells have shown promise in non-human primate models of HIV transmission and as these agents have not yet been broadly introduced in regions of highest HIV prevalence, they are particularly attractive for prophylaxis. We review here the agents that can block HIV cellular entry and that show promise as topical strategies or "virustats" to prevent mucosal transmission of HIV infection PMID:19094217

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    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

  19. Vaginal microbicides and the prevention of HIV transmission

    PubMed Central

    Cutler, Blayne; Justman, Jessica

    2009-01-01

    Worldwide, nearly half of all individuals living with HIV are now women, who acquire the virus largely by heterosexual exposure. With an HIV vaccine likely to be years away, topical microbicide formulations applied vaginally or rectally are being investigated as another strategy for HIV prevention. A review of preclinical and clinical research on the development of microbicides formulated to prevent vaginal HIV transmission yielded 118 studies: 73 preclinical and 45 clinical. Preclinical research included in-vitro assays and cervical explant models, as well as animal models. Clinical research included phase I and II/IIb safety studies, and phase III efficacy studies. Whereas most phase I and phase II clinical trials have found microbicide compounds to be safe and well tolerated, phase III trials completed to date have not demonstrated efficacy in preventing HIV transmission. Topical microbicides are grouped into five classes of agents, based on where they disrupt the pathway of sexual transmission of HIV. These classes include surfactants/membrane disruptors, vaginal milieu protectors, viral entry inhibitors, reverse transcriptase inhibitors, and a fifth group whose mechanism is unknown. The trajectory of microbicide development has been toward agents that block more specific virus—host cell interactions. Microbicide clinical trials face scientifically and ethically complex issues, such as the choice of placebo gel, the potential for viral resistance, and the inclusion of HIV-infected participants. Assessment of combination agents will most likely advance this field of research. PMID:18992405

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

    PubMed

    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

  1. Identification of potent maturation inhibitors against HIV-1 clade C.

    PubMed

    Timilsina, Uddhav; Ghimire, Dibya; Timalsina, Bivek; Nitz, Theodore J; Wild, Carl T; Freed, Eric O; Gaur, Ritu

    2016-01-01

    Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic. PMID:27264714

  2. RNA interference directed to CDK2 inhibits HIV-1 transcription.

    PubMed

    Ammosova, Tatyana; Berro, Reem; Kashanchi, Fatah; Nekhai, Sergei

    2005-10-25

    We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In the present study, CDK2-specific RNA interference in cultured HEK293T cells inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells and potently blocked TNFalpha-induced HIV-1 viral replication in OM10.1 cells. CDK2-specific RNA interference did not have an effect on cell cycle progression, but it augmented TNFalpha-induced apoptosis of OM10.1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target. PMID:16085226

  3. Identification of potent maturation inhibitors against HIV-1 clade C

    PubMed Central

    Timilsina, Uddhav; Ghimire, Dibya; Timalsina, Bivek; Nitz, Theodore J.; Wild, Carl T.; Freed, Eric O.; Gaur, Ritu

    2016-01-01

    Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic. PMID:27264714

  4. Integrin α4β7 expression increases HIV susceptibility in activated cervical CD4+ T cells via an HIV attachment-independent mechanism

    PubMed Central

    Ding, Jian; Tasker, Carley; Lespinasse, Pierre; Dai, Jihong; Fitzgerald-Bocarsly, Patricia; Lu, Wuyuan; Heller, Debra; Chang, Theresa L.

    2015-01-01

    Background CD4+ T cells, the principal target in acute SIV and HIV infection, are crucial for the establishment and dissemination of HIV infection in mucosal tissues. Studies indicate that α4β7 CD4+ T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7+ CD4+ T cells. In vitro all-trans retinoic acid differentiated peripheral CD4+ T cells (at-RA differentiated cells) were included as a comparison. Results In both peripheral and cervical cells, the majority of HIV p24+ cells were activated CD4+ T cells expressing integrin α4β7. Among infected at-RA differentiated cells, the frequency of CCR5 expression was higher in HIV p24+ cells than in HIV p24- cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusion Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells. PMID:26167616

  5. HIV, AIDS, and the Future

    MedlinePlus

    ... 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, ...

  6. HIV / AIDS: An Unequal Burden

    MedlinePlus

    ... 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 ...

  7. HIV/AIDS and Alcohol

    MedlinePlus

    ... 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, ...

  8. HIV, AIDS, and the Future

    MedlinePlus

    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 ...

  9. Women and HIV/AIDS

    MedlinePlus

    ... action on HIV/AIDS National Women and Girls HIV/AIDS Awareness Day – March 10 Programs Share your story Anonymous from Illinois says... Although I am HIV negative, I would like to share my story. ...

  10. HIV/AIDS in Women

    MedlinePlus

    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. HIV often ...

  11. HIV-Positive-to-HIV-Positive Liver Transplantation.

    PubMed

    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

  12. Syndecan-Fc Hybrid Molecule as a Potent In Vitro Microbicidal Anti-HIV-1 Agent▿

    PubMed Central

    Bobardt, Michael D.; Chatterji, Udayan; Schaffer, Lana; de Witte, Lot; Gallay, Philippe A.

    2010-01-01

    In the absence of a vaccine, there is an urgent need for the development of safe and effective topical microbicides to prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1). In this study, we proposed to develop a novel class of microbicides using syndecan as the antiviral agent. Specifically, we generated a soluble syndecan-Fc hybrid molecule by fusing the ectodomain of syndecan-1 to the Fc domain of a human IgG. We then tested the syndecan-Fc hybrid molecule for various in vitro microbicidal anti-HIV-1 properties. Remarkably, the syndecan-Fc hybrid molecule possesses multiple attractive microbicidal properties: (i) it blocks HIV-1 infection of primary targets including T cells, macrophages, and dendritic cells (DC); (ii) it exhibits a broad range of antiviral activity against primary HIV-1 isolates, multidrug resistant HIV-1 isolates, HIV-2, and simian immunodeficiency virus (SIV); (iii) it prevents transmigration of HIV-1 through human primary genital epithelial cells; (iv) it prevents HIV-1 transfer from dendritic cells to CD4+ T cells; (v) it is potent when added 2 h prior to addition of HIV-1 to target cells; (vi) it is potent at a low pH; (vii) it blocks HIV-1 infectivity when diluted in genital fluids; and (viii) it prevents herpes simplex virus infection. The heparan sulfate chains of the syndecan-Fc hybrid molecule are absolutely required for HIV-1 neutralization. Several lines of evidence suggest that the highly conserved Arg298 in the V3 region of gp120 serves as the locus for the syndecan-Fc hybrid molecule neutralization. In conclusion, this study suggests that the syndecan-Fc hybrid molecule represents the prototype of a new generation of microbicidal agents that may have promise for HIV-1 prevention. PMID:20439611

  13. NCCN Evidence Blocks.

    PubMed

    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

  14. Intraocular radiation blocking

    SciTech Connect

    Finger, P.T.; Ho, T.K.; Fastenberg, D.M.; Hyman, R.A.; Stroh, E.M.; Packer, S.; Perry, H.D. )

    1990-09-01

    Iodine-based liquid radiographic contrast agents were placed in normal and tumor-bearing (Greene strain) rabbit eyes to evaluate their ability to block iodine-125 radiation. This experiment required the procedures of tumor implantation, vitrectomy, air-fluid exchange, and 125I plaque and thermoluminescent dosimetry (TLD) chip implantation. The authors quantified the amount of radiation attenuation provided by intraocularly placed contrast agents with in vivo dosimetry. After intraocular insertion of a blocking agent or sham blocker (saline) insertion, episcleral 125I plaques were placed across the eye from episcleral TLD dosimeters. This showed that radiation attenuation occurred after blocker insertion compared with the saline controls. Then computed tomographic imaging techniques were used to describe the relatively rapid transit time of the aqueous-based iohexol compared with the slow transit time of the oil-like iophendylate. Lastly, seven nontumor-bearing eyes were primarily examined for blocking agent-related ocular toxicity. Although it was noted that iophendylate induced intraocular inflammation and retinal degeneration, all iohexol-treated eyes were similar to the control eyes at 7 and 31 days of follow-up. Although our study suggests that intraocular radiopaque materials can be used to shield normal ocular structures during 125I plaque irradiation, a mechanism to keep these materials from exiting the eye must be devised before clinical application.

  15. HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2

    PubMed Central

    Fernández-Oliva, Alberto; Finzi, Andrés; Haim, Hillel; Menéndez-Arias, Luis; Sodroski, Joseph

    2015-01-01

    ABSTRACT Previous studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed in gag, vif, env, and nef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors. IMPORTANCE HIV-1 can infect only humans and chimpanzees. The main reason for this narrow tropism is the presence in many species of dominant-acting factors, known as restriction factors, that block viral replication in a species-specific way. We have been exploring the blocks to HIV-1 in common marmosets, with the ultimate goal of developing a new animal model of HIV-1 infection in these monkeys. In this study, we observed that common marmoset APOBEC3G and BST2, two known restriction factors, are able to block HIV-1 in cell cultures. We have adapted HIV-1 to replicate in the presence of these restriction factors and have characterized the mechanisms of escape. These studies can help in the

  16. Block 3. This photograph depicts the northern view of Block ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Block 3. This photograph depicts the northern view of Block 2 towards the May D & F Tower from the main path along the western facades - Skyline Park, 1500-1800 Arapaho Street, Denver, Denver County, CO

  17. SAMHD1 restricts HIV-1 infection in resting CD4+ T cells

    PubMed Central

    Baldauf, Hanna-Mari; Pan, Xiaoyu; Erikson, Elina; Schmidt, Sarah; Daddacha, Waaqo; Burggraf, Manja; Schenkova, Kristina; Ambiel, Ina; Wabnitz, Guido; Gramberg, Thomas; Panitz, Sylvia; Flory, Egbert; Landau, Nathaniel R; Sertel, Serkan; Rutsch, Frank; Lasitschka, Felix; Kim, Baek; König, Renate; Fackler, Oliver T; Keppler, Oliver T

    2013-01-01

    Unlike activated CD4+ T cells, resting CD4+ T cells are highly resistant to productive HIV-1 infection1–8. Early after HIV-1 entry, a major block limits reverse transcription of incoming viral genomes. Here we show that the deoxynucleoside triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1 RNA in resting CD4+ T cells. SAMHD1 is abundantly expressed in resting CD4+ T cells circulating in peripheral blood and residing in lymphoid organs. The early restriction to infection in unstimulated CD4+ T cells is overcome by HIV-1 or HIV-2 virions into which viral Vpx is artificially or naturally packaged, respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide pools precede successful infection by Vpx-carrying HIV. Resting CD4+ T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Goutières syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4+ T cells in vivo. Bypassing SAMHD1 was insufficient for the release of viral progeny, implicating other barriers at later stages of HIV replication. Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1. PMID:22972397

  18. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    PubMed Central

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  19. The Urgency Of Providing Comprehensive And Integrated Treatment For Substance Abusers With HIV

    PubMed Central

    Volkow, Nora D.; Montaner, Julio

    2011-01-01

    Substance abuse is linked to many new cases of HIV infection. Barriers such as the myth that drug users cannot adhere to HIV/AIDS treatment block progress in curbing the spread of HIV in that population. In this article we explain the need to aggressively seek out high-risk, hard-to-reach substance abusers and to offer them HIV testing, access to treatment, and the necessary support to remain in treatment—both for HIV and for substance abuse. We summarize evidence showing that injection drug users can successfully undergo HIV treatment; that many substance abusers adhere to antiretroviral therapy as well as do people who don’t inject drugs; and that injection drug users who undergo substance abuse treatment are more likely to obtain and stay in treatment for their HIV infection. This evidence makes a strong case for integrating substance abuse treatment with HIV treatment programs and providing substance abusers with universal access to HIV treatment. But an integrated strategy will require changes in the health care system to overcome lingering obstacles that inhibit the merging of substance abuse treatment with HIV programs. PMID:21821558

  20. Barriers to HIV Cure.

    PubMed

    Stein, J; Storcksdieck Genannt Bonsmann, M; Streeck, H

    2016-10-01

    Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers. PMID:27620852

  1. Stimulation of HIV-1 Replication in Immature Dendritic Cells in Contact with Primary CD4 T or B Lymphocytes ▿

    PubMed Central

    Holl, Vincent; Xu, Ke; Peressin, Maryse; Lederle, Alexandre; Biedma, Marina Elizabeth; Delaporte, Maryse; Decoville, Thomas; Schmidt, Sylvie; Laumond, Géraldine; Aubertin, Anne-Marie; Moog, Christiane

    2010-01-01

    Sexual transmission is the major route of HIV-1 infection worldwide. Dendritic cells (DCs) from the mucosal layers are considered to be the initial targets of HIV-1 and probably play a crucial role in HIV-1 transmission. We investigated the role of cell-to-cell contact between HIV-1-exposed immature DCs and various lymphocyte subsets in the stimulation of HIV-1 replication. We found that HIV-1 replication and production in DCs were substantially enhanced by the coculture of DCs with primary CD4 T or nonpermissive B lymphocytes but not with primary activated CD8 T lymphocytes or human transformed CD4 T lymphocytes. Most of the new virions released by cocultures of HIV-1-exposed immature DCs and primary B lymphocytes expressed the DC-specific marker CD1a and were infectious for both immature DCs and peripheral blood mononuclear cells (PBMCs). Cocultured DCs thus produced large numbers of infectious viral particles under these experimental conditions. The soluble factors present in the supernatants of the cocultures were not sufficient to enhance HIV-1 replication in DCs, for which cell-to-cell contact was required. The neutralizing monoclonal antibody IgG1b12 and polyclonal anti-HIV-1 sera efficiently blocked HIV-1 transfer to CD4 T lymphocytes but did not prevent the increase in viral replication in DCs. Neutralizing antibodies thus proved to be more efficient at blocking HIV-1 transfer than previously thought. Our findings show that HIV-1 exploits DC-lymphocyte cross talk to upregulate replication within the DC reservoir. We provide evidence for a novel mechanism that may facilitate HIV-1 replication and transmission. This mechanism may favor HIV-1 pathogenesis, immune evasion, and persistence. PMID:20147388

  2. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.301 Blocked...

  3. View southeast of caps for blocks for JFK; blocks are ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View southeast of caps for blocks for JFK; blocks are used to support ship when it is repositioned to paint inaccessible areas masked by original support blocks. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Carpentry Shop, League Island, Philadelphia, Philadelphia County, PA

  4. HIV Evolution and Escape.

    PubMed Central

    Richman, Douglas D.; Little, Susan J.; Smith, Davey M.; Wrin, Terri; Petropoulos, Christos; Wong, Joseph K.

    2004-01-01

    Human immunodeficiency virus (HIV) exemplifies the principles of Darwinian evolution with a telescoped chronology. Because of its high mutation rate and remarkably high rates of replication, evolution can be appreciated over periods of days in contrast to the durations conceived of by Darwin. Certain selective pressures that drive the evolution of HIV include chemotherapy, anatomic compartmentalization and the immune response. Examples of these selective forces on HIV evolution are described. Images Fig. 5 PMID:17060974

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

    PubMed Central

    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

  6. HIV Associated Opportunistic Pneumonias.

    PubMed

    Ismail, T; Lee, C

    2011-03-01

    Opportunistic pneumonias are major causes of morbidity and mortality in HIV infected individuals. The majority of new HIV infections in Malaysia are adults aged 20 to 39 years old and many are unaware of their HIV status until they present with an opportunistic infection. HIV associated opportunistic pneumonias can progress rapidly without appropriate therapy. Therefore a proper diagnostic evaluation is vital and prompt empiric treatment of the suspected diagnosis should be commenced while waiting for the results of the diagnostic studies. Tuberculosis, Pneumocystis pneumonia (PCP) and recurrent bacterial pneumonias are common causes of AIDS-defining diseases and are discussed in this article. PMID:23765154

  7. Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection

    PubMed Central

    Hanauske-Abel, Hartmut M.; Saxena, Deepti; Palumbo, Paul E.; Hanauske, Axel-Rainer; Luchessi, Augusto D.; Cambiaghi, Tavane D.; Hoque, Mainul; Spino, Michael; Gandolfi, Darlene D'Alliessi; Heller, Debra S.; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M.; Tricta, Fernando; Connelly, John; Popowicz, Anthony M.; Cone, Richard A.; Holland, Bart; Pe’ery, Tsafi; Mathews, Michael B.

    2013-01-01

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

  8. Ear - blocked at high altitudes

    MedlinePlus

    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 ...

  9. Porous block nanofiber composite filters

    DOEpatents

    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).

  10. Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line

    PubMed Central

    Kumar, Amit; Abbas, Wasim; Colin, Laurence; Khan, Kashif Aziz; Bouchat, Sophie; Varin, Audrey; Larbi, Anis; Gatot, Jean-Stéphane; Kabeya, Kabamba; Vanhulle, Caroline; Delacourt, Nadège; Pasquereau, Sébastien; Coquard, Laurie; Borch, Alexandra; König, Renate; Clumeck, Nathan; De Wit, Stephane; Rohr, Olivier; Rouzioux, Christine; Fulop, Tamas; Van Lint, Carine; Herbein, Georges

    2016-01-01

    Akt signaling plays a central role in many biological processes, which are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. We found that Akt interacts with HIV-1 Nef protein. In primary T cells treated with exogenous Nef or acutely infected with Nef-expressing HIV-1 in vitro, Akt became phosphorylated on serine473 and threonine308. In vitro, Akt activation mediated by Nef in T-cells was blocked by HIV protease inhibitors (PI), but not by reverse transcriptase inhibitors (RTI). Ex vivo, we found that the Akt pathway is hyperactivated in peripheral blood lymphocytes (PBLs) from cART naïve HIV-1-infected patients. PBLs isolated from PI-treated patients, but not from RTI-treated patients, exhibited decreased Akt activation, T-cell proliferation and IL-2 production. We found that PI but not RTI can block HIV-1 reactivation in latently infected J-Lat lymphoid cells stimulated with various stimuli. Using luciferase measurement, we further confirmed that Nef-mediated reactivation of HIV-1 from latency in 1G5 cells was blocked by PI parallel to decreased Akt activation. Our results indicate that PI-mediated blockade of Akt activation could impact the HIV-1 reservoir and support the need to further assess the therapeutic use of HIV-1 PI in order to curtail latently infected cells in HIV-1-infected patients. PMID:27076174

  11. Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line.

    PubMed

    Kumar, Amit; Abbas, Wasim; Colin, Laurence; Khan, Kashif Aziz; Bouchat, Sophie; Varin, Audrey; Larbi, Anis; Gatot, Jean-Stéphane; Kabeya, Kabamba; Vanhulle, Caroline; Delacourt, Nadège; Pasquereau, Sébastien; Coquard, Laurie; Borch, Alexandra; König, Renate; Clumeck, Nathan; De Wit, Stephane; Rohr, Olivier; Rouzioux, Christine; Fulop, Tamas; Van Lint, Carine; Herbein, Georges

    2016-01-01

    Akt signaling plays a central role in many biological processes, which are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. We found that Akt interacts with HIV-1 Nef protein. In primary T cells treated with exogenous Nef or acutely infected with Nef-expressing HIV-1 in vitro, Akt became phosphorylated on serine(473) and threonine(308). In vitro, Akt activation mediated by Nef in T-cells was blocked by HIV protease inhibitors (PI), but not by reverse transcriptase inhibitors (RTI). Ex vivo, we found that the Akt pathway is hyperactivated in peripheral blood lymphocytes (PBLs) from cART naïve HIV-1-infected patients. PBLs isolated from PI-treated patients, but not from RTI-treated patients, exhibited decreased Akt activation, T-cell proliferation and IL-2 production. We found that PI but not RTI can block HIV-1 reactivation in latently infected J-Lat lymphoid cells stimulated with various stimuli. Using luciferase measurement, we further confirmed that Nef-mediated reactivation of HIV-1 from latency in 1G5 cells was blocked by PI parallel to decreased Akt activation. Our results indicate that PI-mediated blockade of Akt activation could impact the HIV-1 reservoir and support the need to further assess the therapeutic use of HIV-1 PI in order to curtail latently infected cells in HIV-1-infected patients. PMID:27076174

  12. Using Attribute Blocks with Children

    ERIC Educational Resources Information Center

    Huntsberger, John P.

    1978-01-01

    The classroom use of attribute blocks to develop thinking skills is defended in this article. Divergent-productive thinking is identified as an important skill that can be developed by using these blocks. However, teacher commitment and involvement in the program is considered necessary. Suggestions for using these blocks are included. (MA)

  13. Building Curriculum during Block Play

    ERIC Educational Resources Information Center

    Andrews, Nicole

    2015-01-01

    Blocks are not just for play! In this article, Nicole Andrews describes observing the interactions of three young boys enthusiastically engaged in the kindergarten block center of their classroom, using blocks in a building project that displayed their ability to use critical thinking skills, physics exploration, and the development of language…

  14. Property Blocks: Games and Activities.

    ERIC Educational Resources Information Center

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

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

  15. CORE SATURATION BLOCKING OSCILLATOR

    DOEpatents

    Spinrad, R.J.

    1961-10-17

    A blocking oscillator which relies on core saturation regulation to control the output pulse width is described. In this arrangement an external magnetic loop is provided in which a saturable portion forms the core of a feedback transformer used with the thermionic or semi-conductor active element. A first stationary magnetic loop establishes a level of flux through the saturation portion of the loop. A second adjustable magnet moves the flux level to select a saturation point giving the desired output pulse width. (AEC)

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

    PubMed Central

    Shen, Ruizhong; Achenbach, Jenna; Shen, Yue; Palaia, Jana; Rahkola, Jeremy T.; Nick, Heidi J.; Smythies, Lesley E.; McConnell, Michelle; Fowler, Mary G.; Smith, Phillip D.; Janoff, Edward N.

    2015-01-01

    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. PMID:26680219

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

    PubMed

    Shen, Ruizhong; Achenbach, Jenna; Shen, Yue; Palaia, Jana; Rahkola, Jeremy T; Nick, Heidi J; Smythies, Lesley E; McConnell, Michelle; Fowler, Mary G; Smith, Phillip D; Janoff, Edward N

    2015-01-01

    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. PMID:26680219

  18. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    MedlinePlus

    Side Effects of HIV Medicines HIV and Hepatotoxicity (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Hepatotoxicity means damage to the ... the liver can be life-threatening. What HIV medicines can cause hepatotoxicity? HIV medicines in the following ...

  19. [HIV and reproductive choices].

    PubMed

    Boer, K; de Vries, J W; de Beaufort, I E

    1995-05-13

    It is estimated that there are about 120-150 hemophilic men infected with HIV in the Netherlands as well as 1000 men infected via intravenous drug use. The majority of them are in reproductive age with relationships with seronegative women. In the event they want to have a child, artificial insemination with donor sperm (KID) is an option. In 1994 there were 147 instances of insemination of 66 women with the processed semen of HIV-positive men and no infection resulted. The annual risk of HIV infection was 7.2% of a woman engaging in unprotected intercourse, according to a prospective Italian study. The risk of HIV infection per contact was estimated at 0.1-5.6%. However, it is not yet proven that processed sperm of an HIV-seropositive man can produce a pregnancy without the risk of infecting the woman. The risk of transmission of HIV to the fetus is higher in artificial insemination of a seropositive woman with the sperm of her partner. In vitro fertilization is not a sure method either for the prevention of HIV infection of the mother because of the possibility of an egg cell being infected before fertilization. HIV-infected pregnant women face the problems of caring for HIV-infected offspring. For HIV discordant couples the advice is to use both condoms for the prevention of infection and oral contraceptives for the prevention of pregnancy. In the case of a lesbian relationship, if the partners want to have a child, HIV infection is still a factor because of previous heterosexual contacts. PMID:7753239

  20. Productive Replication of vif-Chimeric HIV-1 in Feline Cells▿

    PubMed Central

    Stern, Melissa A.; Hu, Chunling; Saenz, Dyana T.; Fadel, Hind J.; Sims, Olivia; Peretz, Mary; Poeschla, Eric M.

    2010-01-01

    Nonprimate animal models of HIV-1 infection are prevented by missing cellular cofactors and by antiviral actions of species-specific host defense factors. These blocks are profound in rodents but may be less abundant in certain Carnivora. Here, we enabled productive, spreading replication and passage of HIV-1 in feline cells. Feline fibroblasts, T-cell lines, and primary peripheral blood mononuclear cells supported early and late HIV-1 life cycle phases in a manner equivalent to that of human cells, except that produced virions had low infectivity. Stable expression of feline immunodeficiency virus (FIV) Vif-green fluorescent protein (GFP) in HIV-1 entry receptor-complemented feline (CrFK) cells enabled robust spreading HIV-1 replication. FIV Vif colocalized with feline APOBEC3 (fA3) proteins, targeted them for degradation, and prevented G→A hypermutation of the HIV-1 cDNA by fA3CH and fA3H. HIV-1 Vif was inactive against fA3s as expected and even paradoxically augmented restriction in some assays. In an interesting contrast, simian immunodeficiency virus SIVmac Vif had substantial anti-fA3 activities, which were complete against fA3CH and partial against fA3H. Moreover, both primate lentiviral Vifs colocalized with fA3s and could be pulled down from cell lysates by fA3CH. HIV-1 molecular clones that encode FIV Vif or SIVmac Vif (HIV-1VF and HIV-1VS) were then constructed. These viruses replicated productively in HIV-1 receptor-expressing CrFK cells and could be passaged serially to uninfected cells. Thus, with the exception of entry receptors, the cat genome can supply the dependency factors needed by HIV-1, and a main restriction can be countered by vif chimerism. The results raise the possibility that the domestic cat could yield an animal model of HIV-1 infection. PMID:20463079

  1. Eikonalization of conformal blocks

    SciTech Connect

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

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

  2. Eikonalization of conformal blocks

    DOE PAGESBeta

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the t-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the 'eikonalization' of conformal blocks. We show that when an operator T appears in the OPE Ο(x)Ο(0), then the large spin Fock space states [TT···T]ℓ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an correlator build the classical 'T field' in the dual AdS description. In some limits the sum of all Fock spacemore » exchanges can be represented as the exponential of a single T exchange in the 4-pt correlator of O. Our results should be useful for systematizing 1/ℓ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading log ℓ dependence of Fock space conformal block coefficients, and we directly compute the OPE coefficients of the simplest ‘triple-trace’ operators.« less

  3. Nerve blocks for chronic pain.

    PubMed

    Hayek, Salim M; Shah, Atit

    2014-10-01

    Nerve blocks are often performed as therapeutic or palliative interventions for pain relief. However, they are often performed for diagnostic or prognostic purposes. When considering nerve blocks for chronic pain, clinicians must always consider the indications, risks, benefits, and proper technique. Nerve blocks encompass a wide variety of interventional procedures. The most common nerve blocks for chronic pain and that may be applicable to the neurosurgical patient population are reviewed in this article. This article is an introduction and brief synopsis of the different available blocks that can be offered to a patient. PMID:25240668

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

    PubMed

    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

  5. Living with HIV/AIDS

    MedlinePlus

    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. ...

  6. Positive: HIV Affirmative Counseling.

    ERIC Educational Resources Information Center

    Kain, Craig D.

    At the end of the 1980s, counselors largely lacked an integrated approach to counseling people living with HIV disease. This book describes the experience of counseling this group of persons. The major premise here is that counselors who counsel HIV-positive clients must come to understand and affirm their clients' experiences. The text defines a…

  7. Psychoneuroimmunology and HIV-1.

    ERIC Educational Resources Information Center

    Antoni, Michael H.; And Others

    1990-01-01

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

  8. HIV and Communication

    ERIC Educational Resources Information Center

    McNeilly, L.G.

    2005-01-01

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

  9. Overview of HIV.

    PubMed

    Klimas, Nancy; Koneru, Anne O'Brien; Fletcher, Mary Ann

    2008-06-01

    This article provides an overview and reviews the HIV pandemic, the basic biology and immunology of the virus (e.g., genetic diversity of HIV and the viral life cycle), the phases of disease progression, modes of HIV transmission, HIV testing, immune response to the infection, and current therapeutic strategies. HIV is occurring in epidemic proportions, especially in Sub-Saharan Africa. In the US, men who have sex with men account for over half of AIDS diagnoses; racial and ethnic minorities are disproportionally affected. Factors influencing the progression and severity of HIV infection include type of immune response, coinfection (e.g., another sexually transmitted infection, including hepatitis B or C), age and behavioral and psychosocial factors. Antiretroviral therapies can achieve reduction in blood levels of the HIV virus below the limits of detection by current technology. However, effective treatment requires adherence to therapy. Patient failure to adhere to treatment regimens results in detectible circulating virus and in HIV disease progression, and is the primary cause of drug resistance. In addition to research on the immunology and virology of the disease, other studies focus on behavioral and psychosocial factors that may affect medication adherence and risk behaviors. PMID:18541903

  10. Smart HIV testing system.

    PubMed

    El Kateeb, Ali; Law, Peter; Chan, King

    2005-06-01

    The quick HIV testing method called "MiraWell Rapid HIV Test" uses a specialized testing kit to determine whether an individual's blood is contaminated with the HIV virus or not. When a drop of blood is placed on the center of the testing kit, a simple pattern will appear in the middle of the kit to indicate the test status, i.e., positive or negative. This HIV test should be done in a small clinic or in a lab and the test must be conducted by a trained technician. A smart HIV testing system was developed through this research to eliminate the human error that is associated with the use of the quick HIV testing kits. Also, the smart HIV system will improve the testing productivity in comparison to those achieved by the trained technicians. In this research, we have developed a cost-effective system that analyzes the image produced by the HIV kits. We have used a System-On-Chip (SOC) design approach based on the Field Programmable Gate Array (FPGA) technology and the Xilinx Virtex SOC chip in building the system's prototype. The system used a CMOS digital camera to capture the image and an FPGA chip to process the captured image and send the testing results to the display unit. The system can be used in small clinics and pharmacies and eliminates the need for trained technicians. The system has been tested successfully and 98% of the tests were correct. PMID:16078623

  11. Women and HIV

    MedlinePlus

    ... The impact of HIV is especially great among young women of color. More than one third of new ... legs. Abnormal pre-cancerous cell types related to cervical cancer are more frequent and severe in women who are HIV-positive. See fact sheet 510 ...

  12. Blocks database and its applications.

    PubMed

    Henikoff, J G; Henikoff, S

    1996-01-01

    Protein blocks consist of multiply aligned sequence segments without gaps that represent the most highly conserved regions of protein families. A database of blocks has been constructed by successive application of the fully automated PROTOMAT system to lists of protein family members obtained from Prosite documentation. Currently, Blocks 8.0 based on protein families documented in Prosite 12 consists of 2884 blocks representing 770 families. Searches of the Blocks Database are carried out using protein or DNA sequence queries, and results are returned with measures of significance for both single and multiple block hits. The databse has also proved useful for derivation of amino acid substitution matrices (the Blosum series) and other sets of parameters. WWW and E-mail servers provide access to the database and associated functions, including a block maker for sequences provided by the user. PMID:8743679

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

    PubMed Central

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

    2015-01-01

    The ‘Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database’, available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein–human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12 786 protein–protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14 102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set. PMID:25378338

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

    PubMed Central

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

    2014-01-01

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

  15. HIV Infection Upregulates Caveolin 1 Expression To Restrict Virus Production▿

    PubMed Central

    Lin, Shanshan; Wang, Xiao Mei; Nadeau, Peter E.; Mergia, Ayalew

    2010-01-01

    Caveolin 1 (Cav-1) is a major protein of a specific membrane lipid raft known as caveolae. Cav-1 interacts with the gp41 of the human immunodeficiency virus (HIV) envelope, but the role of Cav-1 in HIV replication and pathogenesis is not known. In this report, we demonstrate that HIV infection in primary human monocyte-derived macrophages (MDMs), THP-1 macrophages, and U87-CD4 cells results in a dramatic upregulation of Cav-1 expression mediated by HIV Tat. The activity of p53 is essential for Tat-induced Cav-1 expression, as our findings show enhanced phosphorylation of serine residues at amino acid positions 15 and 46 in the presence of Tat with a resulting Cav-1 upregulation. Furthermore, inhibition of p38 mitogen-activated protein kinase (MAPK) blocked phosphorylation of p53 in the presence of Tat. Infection studies of Cav-1-overexpressing cells reveal a significant reduction of HIV production. Taken together, these results suggest that HIV infection enhances the expression of Cav-1, which subsequently causes virus reduction, suggesting that Cav-1 may contribute to persistent infection in macrophages. PMID:20610713

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

    PubMed Central

    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

  17. HIV disclosure among adults living with HIV.

    PubMed

    Mayfield Arnold, E; Rice, E; Flannery, D; Rotheram-Borus, M J

    2008-01-01

    Research on disclosure among heterosexual adult person(s) living with HIV (PLH) was reviewed, omitting disclosure of parental HIV to children. Disclosure has been studied within five additional relational contexts: with partners, family members, friends, healthcare professionals and in work settings. Disclosure is higher among women than men, among Latino and white compared to African-American families, and among younger compared to older HIV-positive adults. Most PLH disclose to their sexual partners and family members, yet there is a significant minority who do not disclose. Similarly, rates of disclosure to employers range from 27-68%, suggesting broad variability in perceived consequences of employment disclosures. Of concern, 40% of PLH do not consistently disclose to their healthcare professionals. Rather than examine HIV disclosures in the context of relationships, it is possible to understand disclosures around personal identity. Disclosure decisions are often made to tell everyone (making HIV status a central attribute of one's identity), no one (requiring strategies for securing social support while remaining anonymous) or some people (requiring strategic decisions based on context). Given that disclosure decisions are central to personal identity, future data on disclosure and interventions designed to increase disclosure or comfort with disclosure must focus on communication strategies adopted by PLH to present a coherent identity. PMID:18278618

  18. HIV-Associated Tuberculosis.

    PubMed

    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

  19. Ethical issues in HIV.

    PubMed

    Dhai, Amaboo; Noble, Ray

    2005-04-01

    The number of people with HIV/AIDS continues to increase globally. Women, who represent the subgroup with the fastest rate of increase, are usually informed of their serostatus by the obstetrician/gynaecologist. As treatment of infected women raises a number of ethical issues, an understanding of the theoretical background for ethical decision making is requisite to ensure these problems are resolved within a morally appropriate framework. Vigorous debate has arisen from the tensions between the competing goals of HIV testing, third party disclosure, management of the critically ill HIV-infected woman, infertility management in the background of HIV/AIDS, and gender-based violence as cause or result of acquiring HIV infection. Women may be differently empowered economically, socially and culturally. What may be a satisfactory solution in the context of the USA and Europe may be far from ideal in that of the developing world. PMID:15778114

  20. HIV and neurocognitive dysfunction.

    PubMed

    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

  1. Block copolymer investigations

    NASA Astrophysics Data System (ADS)

    Yufa, Nataliya A.

    The research presented in this thesis deals with various aspects of block copolymers on the nanoscale: their behavior at a range of temperatures, their use as scaffolds, or for creation of chemically striped surfaces, as well as the behavior of metals on block copolymers under the influence of UV light, and the healing behavior of copolymers. Invented around the time of World War II, copolymers have been used for decades due to their macroscopic properties, such as their ability to be molded without vulcanization, and the fact that, unlike rubber, they can be recycled. In recent years, block copolymers (BCPs) have been used for lithography, as scaffolds for nano-objects, to create a magnetic hard drive, as well as in photonic and other applications. In this work we used primarily atomic force microscopy (AFM) and transmission electron microscopy (TEM), described in Chapter II, to conduct our studies. In Chapter III we demonstrate a new and general method for positioning nanoparticles within nanoscale grooves. This technique is suitable for nanodots, nanocrystals, as well as DNA. We use AFM and TEM to demonstrate selective decoration. In Chapters IV and V we use AFM and TEM to study the structure of polymer surfaces coated with metals and self-assembled monolayers. We describe how the surfaces were created, exhibit their structure on the nanoscale, and prove that their macroscopic wetting properties have been altered compared to the original polymer structures. Finally, Chapters VI and VII report out in-situ AFM studies of BCP at high temperatures, made possible only recently with the invention of air-tight high-temperature AFM imaging cells. We locate the transition between disordered films and cylinders during initial ordering. Fluctuations of existing domains leading to domain coarsening are also described, and are shown to be consistent with reptation and curvature minimization. Chapter VII deals with the healing of PS-b-PMMA following AFM-tip lithography or

  2. [Epidemiology of HIV].

    PubMed

    Ledergerber, Bruno; Battegay, Manuel

    2014-08-01

    Globally, an estimated 35 million people were living with HIV in 2012; of these, 69 % in sub-Saharan Africa. There were 2.3 million new HIV infections globally and 1.6 million AIDS deaths in 2012. As a result of large roll-out programs with integrated voluntary counselling and testing and prevention programs in resource limited settings, sexual transmission of HIV decreased substantially over the last years. However, the world is not on track to reduced HIV transmission among people who inject drugs. Especially in Eastern Europe and Asia prevention coverage for people who inject drugs remains low. In addition, effective prevention among these people is undermined by stigmatisation, discrimination, punitive policy frameworks and law enforcement practices, which discourage people from seeking the health and social services they need. Antiretroviral coverage among pregnant women living with HIV reached 62 % in 2012 resulting in a reduction of newly infected children by 35 % from 2009. In 2012, 9.7 million people in low and middle-income countries received antiretroviral therapy, representing 61 % of all who were eligible under the 2010 WHO HIV treatment guidelines. Under the 2013 guidelines, this represents only 34 % of the 28.3 million people eligible in 2013. A new concept to curb the HIV epidemic is "Test and Treat" which involves population-wide HIV tests with immediate initiation of antiretroviral therapy among all HIV infected individuals. However, there are concerns regarding the sustainability of such treatment programs for decades due to lost to follow up and insufficient adherence and the danger of a large increase of resistant HIV which jeopardize the effectiveness of affordable treatments. PMID:25093307

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

    PubMed Central

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

    2015-01-01

    SUMMARY The C-C chemokine receptor type 5 (CCR5) is a receptor expressed by T-cells and macrophages that serves as a co-receptor for macrophage-tropic HIV-1. Loss of CCR5 is associated with resistance to HIV-1. Here we combine the live cell-based SELEX with high throughput sequencing technology to generate CCR5 RNA aptamers capable of specifically targeting HIV-1 susceptible cells (as siRNA delivery agent) and inhibiting HIV-1 infectivity (as antiviral agent) via block of the CCR5 required for HIV-1 to enter cells. One of the best candidates, G-3, efficiently bound and was internalized into human CCR5 expressing cells. The G-3 specifically neutralized R5 virus infection in primary peripheral blood mononuclear cells, and in vivo generated human CD4+ T cells with a nanomolar IC50. G-3 was also capable of transferring functional siRNAs to CCR5 expressing cells. Collectively, the cell-specific, internalizing, CCR5-targeted aptamers and aptamer-siRNA conjugates offer promise for overcoming some of the current challenges of drug resistance in HIV-1 by providing cell-type- or tissue-specific delivery of various therapeutic moieties. PMID:25754473

  4. Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix.

    PubMed Central

    Freed, E O; Martin, M A

    1995-01-01

    Incorporation of envelope glycoproteins into a budding retrovirus is an essential step in the formation of an infectious virus particle. By using site-directed mutagenesis, we identified specific amino acid residues in the matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein that are critical to the incorporation of HIV-1 envelope glycoproteins into virus particles. Pseudotyping analyses were used to demonstrate that two heterologous envelope glycoproteins with short cytoplasmic tails (the envelope of the amphotropic murine leukemia virus and a naturally truncated HIV-2 envelope) are efficiently incorporated into HIV-1 particles bearing the matrix mutations. Furthermore, deletion of the cytoplasmic tail of HIV-1 transmembrane envelope glycoprotein gp41 from 150 to 7 or 47 residues reversed the incorporation block imposed by the matrix mutations. These results suggest the existence of a specific functional interaction between the HIV-1 matrix and the gp41 cytoplasmic tail. PMID:7853546

  5. STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier.

    PubMed

    Chaudhuri, Anathbandhu; Yang, Bo; Gendelman, Howard E; Persidsky, Yuri; Kanmogne, Georgette D

    2008-02-15

    The relationship among neuroinflammation, blood-brain barrier (BBB) dysfunction, and progressive HIV-1 infection as they affect the onset and development of neuroAIDS is incompletely understood. One possible link is signal transducers and activators of transcription (STATs) pathways. These respond to proinflammatory and regulatory factors and could affect neuroinflammatory responses induced from infected cells and disease-affected brain tissue. Our previous works demonstrated that HIV-1 activates pro-inflammatory and interferon-alpha-inducible genes in human brain microvascular endothelial cells (HBMECs) and that these genes are linked to the Janus kinase (JAK)/STAT pathway. We now demonstrate that HIV-1 activates STAT1, induces IL-6 expression, and diminishes expression of claudin-5, ZO-1, and ZO-2 in HBMECs. The STAT1 inhibitor, fludarabine, blocked HIV-1-induced IL-6, diminished HIV-1-induced claudin-5 and ZO-1 down-regulation, and blocked HIV-1- and IL-6-induced monocyte migration across a BBB model. Enhanced expression and activation of STAT1 and decreased claudin-5 were observed in microvessels from autopsied brains of patients with HIV-1-associated dementia. These data support the notion that STAT1 plays an integral role in HIV-1-induced BBB damage and is relevant to viral neuropathogenesis. Inhibition of STAT1 activation could provide a unique therapeutic strategy to attenuate HIV-1-induced BBB compromise and as such improve clinical outcomes. PMID:18003888

  6. Rotating ice blocks

    NASA Astrophysics Data System (ADS)

    Dorbolo, Stephane; Adami, Nicolas; Grasp Team

    2014-11-01

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

  7. Interpleural block - part 1.

    PubMed

    Dravid, R M; Paul, R E

    2007-10-01

    Interpleural blockade is effective in treating unilateral surgical and nonsurgical pain from the chest and upper abdomen in both the acute and chronic settings. It has been shown to provide safe, high-quality analgesia after cholecystectomy, thoracotomy, renal and breast surgery, and for certain invasive radiological procedures of the renal and hepatobiliary systems. It has also been used successfully in the treatment of pain from multiple rib fractures, herpes zoster, complex regional pain syndromes, thoracic and abdominal cancer, and pancreatitis. The technique is simple to learn and has both few contra-indications and a low incidence of complications. In the first of two reviews, the authors cover the history, taxonomy and anatomical considerations, the spread of local anaesthetic, and the mechanism of action, physiological, pharmacological and technical considerations in the performance of the block. PMID:17845657

  8. Radiation Blocking Lenses

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Biomedical Optical Company of America's Eagle 475 lens absorbs 100 percent of all photowavelengths considered hazardous to eye tissue, including ultraviolet and blue light, which are considered contributors to cataract and age-related macular degeneration. The lens absorbs hazardous wavelengths, but allows a higher percentage of visually useful areas of the spectrum to pass through. Polarization blocks out irritating glint and glare and heightens visual acuity. The Eagle 475 sunglasses are the latest in a series of spinoffs that originated at the Jet Propulsion Laboratory where two scientists developed a protective, welding curtain that filtered out harmful irradiance. The result was a commercial curtain that absorbs filters and scatters light, providing protection for personnel in welding areas. Further research focused on protective industrial glasses and later on consumer products.

  9. Blanket integrated blocking diodes

    NASA Astrophysics Data System (ADS)

    Uebele, P.; Kasper, C.; Rasch, K.-D.

    1986-11-01

    Two types of large area protection diodes for integration in solar arrays were developed in planar technology. For application in a bus voltage concept of V sub bus = 80 V a p-doped blanket integrated blocking diode (p-IBD) was developed with V sub rev = 120 V, whereas for the high voltage concept of V sub bus = 160 V a n-IBD with V sub rev = 250 V was developed. Application as blanket integrated shunt diodes is recommended. The optimized rearside diffusion provides a low forward voltage drop in the temperature range of minus 100 to plus 150 C. As a consequence of planar technology metallized coverglasses have to be used to minimize the photocurrent.

  10. Spintronics: Conceptual Building Blocks

    NASA Astrophysics Data System (ADS)

    Ansermet, J.-Ph.

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

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

    PubMed Central

    2011-01-01

    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. PMID:22145853

  12. HIV treatment for prevention.

    PubMed

    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

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

    SciTech Connect

    McClure, Janela; Margineantu, Daciana H.; Sweet, Ian R.; Polyak, Stephen J.

    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.

  14. Large Block Test Final Report

    SciTech Connect

    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

  15. The HIV-1 transgenic rat model of neuroHIV

    PubMed Central

    Vigorito, Michael; Connaghan, Kaitlyn P.; Chang, Sulie L.

    2016-01-01

    Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse. PMID:25733103

  16. Improved ultrasonic standard reference blocks

    NASA Technical Reports Server (NTRS)

    Eitzen, D. G.; Sushinsky, G. F.; Chwirut, D. J.; Bechtoldt, C. J.; Ruff, A. W.

    1976-01-01

    A program to improve the quality, reproducibility and reliability of nondestructive testing through the development of improved ASTM-type ultrasonic reference standards is described. Reference blocks of aluminum, steel, and titanium alloys are to be considered. Equipment representing the state-of-the-art in laboratory and field ultrasonic equipment was obtained and evaluated. RF and spectral data on ten sets of ultrasonic reference blocks have been taken as part of a task to quantify the variability in response from nominally identical blocks. Techniques for residual stress, preferred orientation, and micro-structural measurements were refined and are applied to a reference block rejected by the manufacturer during fabrication in order to evaluate the effect of metallurgical condition on block response. New fabrication techniques for reference blocks are discussed and ASTM activities are summarized.

  17. What Are Nerve Blocks for Headache?

    MedlinePlus

    ... nerve blocks for headache? Print Email What are nerve blocks for headache? ACHE Newsletter Sign up for ... entering your e-mail address below. What are nerve blocks for headache? A nerve block is the ...

  18. Flazinamide, a novel {beta}-carboline compound with anti-HIV actions

    SciTech Connect

    Wang Yunhua; Tang Jianguo; Wang Ruirui; Yang Liumeng; Dong Zejun; Du Li; Shen Xu; Liu Jikai; Zheng Yongtang . E-mail: zhengyt@mail.kiz.ac.cn

    2007-04-20

    A {beta}-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)-{beta}-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 {mu}M, 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 {mu}M, 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 {mu}M, 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.

  19. Covariant approaches to superconformal blocks

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    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 -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.

  20. HIV Molecular Immunology 2014

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.

    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.

  1. HIV infections in otolaryngology

    PubMed Central

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

    2012-01-01

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

  2. 31 CFR 589.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 589.301 Section 589.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY UKRAINE RELATED SANCTIONS...

  3. 31 CFR 544.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 544.301 Section 544.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION...

  4. 31 CFR 544.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 544.301 Section 544.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION...

  5. 31 CFR 544.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 544.301 Section 544.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION...

  6. 31 CFR 544.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 544.301 Section 544.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION...

  7. 31 CFR 544.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 544.301 Section 544.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS...

  8. 31 CFR 576.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 576.301 Section 576.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY...

  9. 31 CFR 576.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 576.301 Section 576.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY...

  10. 31 CFR 576.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 576.301 Section 576.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY...

  11. 31 CFR 576.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 576.301 Section 576.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY...

  12. 31 CFR 558.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 558.301 Section 558.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOUTH SUDAN SANCTIONS REGULATIONS...

  13. 31 CFR 545.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 545.301 Section 545.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN)...

  14. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  15. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  16. 31 CFR 552.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 552.301 Section 552.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY YEMEN SANCTIONS REGULATIONS...

  17. 31 CFR 552.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 552.301 Section 552.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY YEMEN SANCTIONS REGULATIONS...

  18. 31 CFR 594.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 594.301 Section 594.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM...

  19. 31 CFR 541.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 541.301 Section 541.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS...

  20. 31 CFR 562.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 562.301 Section 562.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES...

  1. 31 CFR 562.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 562.301 Section 562.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General Definitions §...

  2. 31 CFR 562.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 562.301 Section 562.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES...

  3. 31 CFR 562.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 562.301 Section 562.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General Definitions §...

  4. 31 CFR 548.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 548.301 Section 548.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS...

  5. Block 3. Central view of Block 3 observed from the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Block 3. Central view of Block 3 observed from the west to the east. This photograph reveals the alignment of trees within the central path of the park. In addition, this photograph exposes broken bricks aligning tree beds - Skyline Park, 1500-1800 Arapaho Street, Denver, Denver County, CO

  6. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES...

  7. 31 CFR 549.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 549.301 Section 549.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY LEBANON SANCTIONS REGULATIONS...

  8. 31 CFR 549.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 549.301 Section 549.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY LEBANON SANCTIONS REGULATIONS...

  9. 31 CFR 549.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 549.301 Section 549.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY LEBANON SANCTIONS REGULATIONS...

  10. 31 CFR 549.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 549.301 Section 549.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY LEBANON SANCTIONS REGULATIONS...

  11. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS...

  12. 31 CFR 541.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 541.301 Section 541.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS REGULATIONS...

  13. 31 CFR 541.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 541.301 Section 541.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS REGULATIONS...

  14. 31 CFR 541.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 541.301 Section 541.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS REGULATIONS...

  15. 31 CFR 541.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 541.301 Section 541.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS REGULATIONS...

  16. HIV-negative and HIV-positive gay men's attitudes to medicines, HIV treatments and antiretroviral-based prevention.

    PubMed

    Holt, Martin; Murphy, Dean; Callander, Denton; Ellard, Jeanne; Rosengarten, Marsha; Kippax, Susan; de Wit, John

    2013-07-01

    We assessed attitudes to medicines, HIV treatments and antiretroviral-based prevention in a national, online survey of 1,041 Australian gay men (88.3% HIV-negative and 11.7% HIV-positive). Multivariate analysis of variance was used to identify the effect of HIV status on attitudes. HIV-negative men disagreed with the idea that HIV drugs should be restricted to HIV-positive people. HIV-positive men agreed and HIV-negative men disagreed that taking HIV treatments was straightforward and HIV-negative men were more sceptical about whether HIV treatment or an undetectable viral load prevented HIV transmission. HIV-negative and HIV-positive men had similar attitudes to pre-exposure prophylaxis but divergent views about 'treatment as prevention'. PMID:23001412

  17. HIV transmission biology: translation for HIV prevention.

    PubMed

    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

  18. Characterizing the inverses of block tridiagonal, block Toeplitz matrices

    NASA Astrophysics Data System (ADS)

    Boffi, Nicholas M.; Hill, Judith C.; Reuter, Matthew G.

    2015-01-01

    We consider the inversion of block tridiagonal, block Toeplitz matrices and comment on the behaviour of these inverses as one moves away from the diagonal. Using matrix Möbius transformations, we first present an O(1) representation (with respect to the number of block rows and block columns) for the inverse matrix and subsequently use this representation to characterize the inverse matrix. There are four symmetry-distinct cases where the blocks of the inverse matrix (i) decay to zero on both sides of the diagonal, (ii) oscillate on both sides, (iii) decay on one side and oscillate on the other and (iv) decay on one side and grow on the other. This characterization exposes the necessary conditions for the inverse matrix to be numerically banded and may also aid in the design of preconditioners and fast algorithms. Finally, we present numerical examples of these matrix types.

  19. A Shifted Block Lanczos Algorithm 1: The Block Recurrence

    NASA Technical Reports Server (NTRS)

    Grimes, Roger G.; Lewis, John G.; Simon, Horst D.

    1990-01-01

    In this paper we describe a block Lanczos algorithm that is used as the key building block of a software package for the extraction of eigenvalues and eigenvectors of large sparse symmetric generalized eigenproblems. The software package comprises: a version of the block Lanczos algorithm specialized for spectrally transformed eigenproblems; an adaptive strategy for choosing shifts, and efficient codes for factoring large sparse symmetric indefinite matrices. This paper describes the algorithmic details of our block Lanczos recurrence. This uses a novel combination of block generalizations of several features that have only been investigated independently in the past. In particular new forms of partial reorthogonalization, selective reorthogonalization and local reorthogonalization are used, as is a new algorithm for obtaining the M-orthogonal factorization of a matrix. The heuristic shifting strategy, the integration with sparse linear equation solvers and numerical experience with the code are described in a companion paper.

  20. BCL11B is a General Transcriptional Repressor of the HIV-1 Long Terminal Repeat in T Lymphocytes through recruitment of the NuRD Complex

    PubMed Central

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

    2008-01-01

    In this study we provide evidence that the transcription factor BCL11B represses expression from the HIV-1 long terminal repeat (LTR) in T lymphocytes through direct association with the HIV-1 LTR. We also demonstrate that the NuRD corepressor complex mediates BCL11B transcriptional repression of the HIV-1 LTR. In addition, BCL11B and the NuRD complex repressed TAT-mediated transactivation of the HIV-1 LTR in T lymphocytes, pointing to a potential role in initiation of silencing. In support of all the above results, we demonstrate that BCL11B affects HIV-1 replication and virus production, most likely by blocking LTR transcriptional activity. BCL11B showed specific repression for the HIV-1 LTR sequences isolated from seven different HIV-1 subtypes, demonstrating that it is a general transcriptional repressor for all LTRs. PMID:18768194

  1. HIV Genotypic Resistance Testing

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? HIV Antiretroviral Drug Resistance Testing, Genotypic Share this page: Was this page helpful? Also known as: Anti-retroviral Drug Resistance Testing; ARV Resistance Testing Formal name: ...

  2. Travelers' Health: HIV Infection

    MedlinePlus

    ... 448-4911 ( www.nccc.ucsf.edu ). HIV TESTING REQUIREMENTS FOR US TRAVELERS ENTERING FOREIGN COUNTRIES International travelers ... extended stay should review that country’s policies and requirements. This information is usually available from the consular ...

  3. HIV/AIDS Medicines

    MedlinePlus

    ... few years. But today, there are many effective medicines to fight the infection, and people with HIV ... healthier lives. There are five major types of medicines: Reverse transcriptase (RT) inhibitors - interfere with a critical ...

  4. [HIV infection and immigration].

    PubMed

    Monge, Susana; Pérez-Molina, José A

    2016-01-01

    Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care. PMID:27016136

  5. Get Tested for HIV

    MedlinePlus

    ... Why Get Tested? 4 of 7 sections Take Action! Take Action: Get Tested Take these steps to protect yourself ... section Testing Options 5 of 7 sections Take Action: Protect Yourself Protect yourself from HIV. The best ...

  6. Get Tested for HIV

    MedlinePlus

    ... Beware: Online you can buy several HIV home test kits that are not approved by the FDA. Many ... This publication explains how the FDA-approved home test kit works, and warns consumers about purchasing home tests ...

  7. HIV and Viral Hepatitis

    MedlinePlus

    ... prevalent among blacks as among whites. Viral Hepatitis Transmission People can be infected with the three most ... risk for HAV. • • New data suggest that sexual transmission of HCV among MSM with HIV occurs more ...

  8. HIV and Kidney Disease

    MedlinePlus

    ... FOR KIDNEY DISEASE? HIV MEDICATIONS AND THE KIDNEYS DIALYSIS AND KIDNEY TRANSPLANTATION THE BOTTOM LINE WHY SHOULD ... disease (ESRD) or kidney failure. This can require dialysis or a kidney transplant. The rate of kidney ...

  9. HIV Antibody Test

    MedlinePlus

    ... despite the fact that the person is infected ( false negative ). If an HIV antibody test is negative ... infection (around 28 days) and may give a false-negative result. ^ Back to top Is there anything ...

  10. Reduce HIV Risk

    MedlinePlus

    ... incidence could be reduced if people changed their sexual behaviors. Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Spring 2008 ...

  11. Mouth Problems and HIV

    MedlinePlus

    ... orientation. This information is for people who have mouth (oral) problems related to HIV infection. It explains ... look like. It also describes where in the mouth they occur and how they are treated. They ...

  12. Children and HIV

    MedlinePlus

    ... have a different response to HIV infection. CD4 cell counts (see fact sheet 124) and viral load counts ( ... to ARVs. They have larger increases in CD4 cell counts and more diverse CD4 cells. They seem to ...

  13. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  14. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  15. HIV/AIDS

    MedlinePlus

    ... approved by the FDA. Follow instructions on the packaging to ensure the results are as accurate as ... sex practices , such as using latex condoms, are effective in preventing the spread of HIV. But there ...

  16. Classical Virasoro irregular conformal block

    NASA Astrophysics Data System (ADS)

    Rim, Chaiho; Zhang, Hong

    2015-07-01

    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.

  17. MISR Center Block Time Tool

    Atmospheric Science Data Center

    2013-04-01

      MISR Center Block Time Tool The misr_time tool calculates the block center times for MISR Level 1B2 files. This is ... version of the IDL package or by using the IDL Virtual Machine application. The IDL Virtual Machine is bundled with IDL and is ...

  18. Blocking in multirate interconnection networks

    NASA Astrophysics Data System (ADS)

    Valdimarsson, Einir

    1994-02-01

    We present an extension of the classical methods used to evaluate blocking probability. This method is applicable to multirate circuit and fast packet/ATM switching systems. The analytical methods are presented and compared with simulation results using Benes networks as an example. Extensive simulation has been performed focusing on ways to reduce blocking to acceptable levels.

  19. Adjustable-Angle Drill Block

    NASA Technical Reports Server (NTRS)

    Gallimore, F. H.

    1986-01-01

    Adjustable angular drill block accurately transfers hole patterns from mating surfaces not normal to each other. Block applicable to transfer of nonperpendicular holes in mating contoured assemblies in aircraft industry. Also useful in general manufacturing to transfer mating installation holes to irregular and angular surfaces.

  20. Block Transfer Agreement Evaluation Project

    ERIC Educational Resources Information Center

    Bastedo, Helena

    2010-01-01

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

  1. Targeting IκB proteins for HIV latency activation: the role of individual IκB and NF-κB proteins.

    PubMed

    Fernandez, Guerau; Zaikos, Thomas D; Khan, Sohrab Z; Jacobi, Ashley M; Behlke, Mark A; Zeichner, Steven L

    2013-04-01

    Latently infected cell reservoirs represent the main barrier to HIV eradication. Combination antiretroviral therapy (cART) effectively blocks viral replication but cannot purge latent provirus. One approach to HIV eradication could include cART to block new infections plus an agent to activate latent provirus. NF-κB activation induces HIV expression, ending latency. Before activation, IκB proteins sequester NF-κB dimers in the cytoplasm. Three canonical IκBs, IκBα, IκBβ, and IκBε, exist, but the IκB proteins' role in HIV activation regulation is not fully understood. We studied the effects on HIV activation of targeting IκBs by single and pairwise small interfering RNA (siRNA) knockdown. After determining the relative abundance of the IκBs, the relative abundance of NF-κB subunits held by the IκBs, and the kinetics of IκB degradation and resynthesis following knockdown, we studied HIV activation by IκB knockdown, in comparison with those of known HIV activators, tumor necrosis factor alpha (TNF-α), tetradecanoyl phorbol acetate (TPA), and trichostatin A (TSA), in U1 monocytic and J-Lat 10.6 lymphocytic latently infected cells. We found that IκBα knockdown activated HIV in both U1 and J-Lat 10.6 cells, IκBβ knockdown did not activate HIV, and, surprisingly, IκBε knockdown produced the most HIV activation, comparable to TSA activation. Our data show that HIV reactivation can be triggered by targeting two different IκB proteins and that IκBε may be an effective target for HIV latency reactivation in T-cell and macrophage lineages. IκBε knockdown may offer attractive therapeutic advantages for HIV activation because it is not essential for mammalian growth and development and because new siRNA delivery strategies may target siRNAs to HIV latently infected cells. PMID:23365428

  2. Improved ultrasonic standard reference blocks

    NASA Technical Reports Server (NTRS)

    Eitzen, D. G.

    1975-01-01

    A program to improve the quality, reproducibility and reliability of nondestructive testing through the development of improved ASTM-type ultrasonic reference standards is described. Reference blocks of aluminum, steel, and titanium alloys were considered. Equipment representing the state-of-the-art in laboratory and field ultrasonic equipment was obtained and evaluated. Some RF and spectral data on ten sets of ultrasonic reference blocks were taken as part of a task to quantify the variability in response from nominally identical blocks. Techniques for residual stress, preferred orientation, and microstructural measurements were refined and are applied to a reference block rejected by the manufacturer during fabrication in order to evaluate the effect of metallurgical condition on block response.

  3. Nutrition and HIV.

    PubMed

    Highleyman, Liz

    2006-01-01

    Good nutrition is key to a healthy lifestyle, regardless of whether one is living with HIV/AIDS. Optimal nutrition can help boost immune function, maximize the effectiveness of antiretroviral therapy, reduce the risk of chronic illnesses such as diabetes and cardiovascular disease, and contribute to a better overall quality of life. In the early years of the AIDS epidemic, many people with HIV were dealing with wasting and opportunistic infections (OIs) linked to unsafe food or water. While these problems are less common today in developed countries with widespread access to highly active antiretroviral therapy (HAART), many HIV positive people have traded these concerns for worries about body shape changes, elevated blood lipids, and other metabolic complications associated with antiretroviral therapy. Fortunately, maintaining a healthy diet can help address these problems. As HIV positive people live longer thanks to effective treatment, good nutrition can also help prevent problems (such as bone loss) associated with normal aging. But there is no single, optimal eating regimen appropriate for every person living with HIV/AIDS. Instead, HIV positive people should adopt a sensible balanced diet and consult an experienced nutrition specialist for individualized recommendations. PMID:16610116

  4. HIV in Europe.

    PubMed

    Põder, Airi; Haldre, Madli

    2014-01-01

    In 2011, the estimated number of people living with HIV in Europe and Central Asia was 2.3 million. This is more than twice the 2001 figure. At the same time, approximately 50% of the infected people may not know their HIV status. The Europe/Central Asia region is one of only two regions in which HIV infections continue to increase. The estimated prevalence rate in the west and center of the region, however, has remained stable at 0.2%. The HIV epidemics in Eastern Europe and Central Asia are typically driven by unsafe drug injection and by onward transmission to the sexual partners of people who inject drugs. In the western part of the region, the epidemic remains concentrated among men who have sex with men and migrants from countries with generalized epidemics. Means of preventing and fighting HIV should, first and foremost, be directed to those parts of the population that are most exposed to the risk of the infection. Proceeding from the data presented, recommendations are given for ways of decreasing HIV prevalence in the region, such as promoting dialogue and awareness among multistakeholders, including policy makers, donors, and population groups most exposed to the infection. PMID:24559564

  5. Microbial exposure alters HIV-1-induced mucosal CD4+ T cell death pathways Ex vivo

    PubMed Central

    2014-01-01

    Background Early HIV-1 infection causes massive CD4+ T cell death in the gut and translocation of bacteria into the circulation. However, the programmed cell death (PCD) pathways used by HIV-1 to kill CD4+ T cells in the gut, and the impact of microbial exposure on T cell loss, remain unclear. Understanding mucosal HIV-1 triggered PCD could be advanced by an ex vivo system involving lamina propria mononuclear cells (LPMCs). We therefore modeled the interactions of gut LPMCs, CCR5-tropic HIV-1 and a commensal gut bacterial species, Escherichia coli. In this Lamina Propria Aggregate Culture (LPAC) model, LPMCs were infected with HIV-1BaL by spinoculation and cultured in the presence or absence of heat killed E.coli. CD4+ T cell numbers derived from flow cytometry and viable cell counts were reported relative to mock infection. Viable cells were identified by viability dye exclusion (AqVi), and intracellular HIV-1 Gag p24 protein was used to identify infected cells. Annexin V and AqVi were used to identify apoptotic versus necrotic cells. Caspase-1 and Caspase-3 activities were blocked using specific inhibitors YVAD and DEVD, respectively. Results CD4+ T cell depletion following HIV-1 infection was reproducibly observed by 6 days post infection (dpi). Depletion at 6 dpi strongly correlated with infection frequency at 4 dpi, was significantly blocked by Efavirenz treatment, and was primarily driven by p24-negative cells that were predominantly necrotic. HIV-1 infection significantly induced CD4+ T-cell intrinsic Caspase-1 activity, whereas Caspase-1 inhibition, but not Caspase-3 inhibition, significantly blocked CD4+ T cell depletion. Exposure to E.coli enhanced HIV-1 infection and CD4+ T depletion, and significantly increased the number of apoptotic p24+ cells. Notably, CD4+ T cell depletion in the presence of E.coli was partially blocked by Caspase-3, but not by Caspase-1 inhibition. Conclusions In the LPAC model, HIV-1 induced Caspase-1 mediated pyroptosis in

  6. Atrioventricular block after ASD closure

    PubMed Central

    Asakai, Hiroko; Weskamp, Sofia; Eastaugh, Lucas; d'Udekem, Yves; Pflaumer, Andreas

    2016-01-01

    Objective Secundum atrial septal defect (ASD) is a common congenital heart defect. There is limited data on both early and late atrioventricular (AV) block post ASD closure. The aim of this study was to determine the incidence and risk factors of AV block associated with ASD closure. Methods A retrospective analysis of all patients who underwent ASD closure either with a device or surgical method at the Royal Children's Hospital Melbourne between 1996 and 2010 was performed. Baseline demographics, procedural details and follow-up data were collected from medical records. Results A total of 378 patients were identified; 242 in the device group and 136 in the surgical group. Fourteen patients (3.7%) had AV block (1 with second degree and 13 with first degree) at a median follow-up of 28 months; 11/242 (4.5%) in the device group and 3/135 (2.2%) in the surgical group (p=0.39). Six patients had new-onset AV block after ASD closure. In the device subgroup, patients with AV block at follow-up had a larger indexed device size compared with those without (22 (15–31) vs 18(7–38), p=0.02). Multivariate analysis revealed the presence of AV block either pre procedure or post procedure to be the only variables associated with late AV block. Conclusions Late AV block in patients with repaired ASD is rare and most likely independent of the technique used. In the device subgroup, the only risk factor identified to be associated with late AV block was the presence of either preprocedural or postprocedural AV block, so long-term follow-up for these patients should be provided. PMID:27540418

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

    PubMed

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

    2014-01-01

    Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs. PMID:24489923

  8. The Root Extract of the Medicinal Plant Pelargonium sidoides Is a Potent HIV-1 Attachment Inhibitor

    PubMed Central

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

    2014-01-01

    Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs. PMID:24489923

  9. Coping with Viral Diversity in HIV Vaccine Design

    PubMed Central

    Nickle, David C; Rolland, Morgane; Jensen, Mark A; Pond, Sergei L. Kosakovsky; Deng, Wenjie; Seligman, Mark; Heckerman, David; Mullins, James I; Jojic, Nebojsa

    2007-01-01

    The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus. PMID:17465674

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

    PubMed

    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. Curcumin inhibits HIV-1 by promoting Tat protein degradation

    PubMed Central

    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

  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. Student Guide.

    ERIC Educational Resources Information Center

    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…

  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. Instructor Guide.

    ERIC Educational Resources Information Center

    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…

  14. Side Effects of HIV Medicines: HIV and Rash

    MedlinePlus

    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 ... health care provider tells you to. What HIV medicines can cause a hypersensitivity reaction? Nevirapine (brand name: ...

  15. Side Effects of HIV Medicines: HIV and Lipodystrophy

    MedlinePlus

    Side Effects of HIV Medicines HIV and Lipodystrophy (Last updated 9/13/2016; last reviewed 1/7/2016) Key Points Lipodystrophy refers to the changes ... loss on the face and leg . Which HIV medicines are linked to lipodystrophy? Although more research is ...

  16. Side Effects of HIV Medicines: HIV and Diabetes

    MedlinePlus

    Side Effects of HIV Medicines HIV and Diabetes (Last updated 9/13/2016; last reviewed 1/7/2016) Key Points Diabetes is a disease in ... are also infected with hepatitis C. What HIV medicines increase the risk of type 2 diabetes? Some ...

  17. Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum

    PubMed Central

    Friedman, James; Alam, S. Munir; Shen, Xiaoying; Xia, Shi-Mao; Stewart, Shelley; Anasti, Kara; Pollara, Justin; Fouda, Genevieve G.; Yang, Guang; Kelsoe, Garnett; Ferrari, Guido; Tomaras, Georgia D.; Haynes, Barton F.; Liao, Hua-Xin

    2012-01-01

    Background Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. Methods We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). Results The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. Conclusions These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces. PMID:22624058

  18. Bioinformatic Analysis of HIV-1 Entry and Pathogenesis

    PubMed Central

    Aiamkitsumrit, Benjamas; Dampier, Will; Antell, Gregory; Rivera, Nina; Martin-Garcia, Julio; Pirrone, Vanessa; Nonnemacher, Michael R.; Wigdahl, Brian

    2015-01-01

    The evolution of human immunodeficiency virus type 1 (HIV-1) with respect to co-receptor utilization has been shown to be relevant to HIV-1 pathogenesis and disease. The CCR5-utilizing (R5) virus has been shown to be important in the very early stages of transmission and highly prevalent during asymptomatic infection and chronic disease. In addition, the R5 virus has been proposed to be involved in neuroinvasion and central nervous system (CNS) disease. In contrast, the CXCR4-utilizing (X4) virus is more prevalent during the course of disease progression and concurrent with the loss of CD4+ T cells. The dual-tropic virus is able to utilize both co-receptors (CXCR4 and CCR5) and has been thought to represent an intermediate transitional virus that possesses properties of both X4 and R5 viruses that can be encountered at many stages of disease. The use of computational tools and bioinformatic approaches in the prediction of HIV-1 co-receptor usage has been growing in importance with respect to understanding HIV-1 pathogenesis and disease, developing diagnostic tools, and improving the efficacy of therapeutic strategies focused on blocking viral entry. Current strategies have enhanced the sensitivity, specificity, and reproducibility relative to the prediction of co-receptor use; however, these technologies need to be improved with respect to their efficient and accurate use across the HIV-1 subtypes. The most effective approach may center on the combined use of different algorithms involving sequences within and outside of the env-V3 loop. This review focuses on the HIV-1 entry process and on co-receptor utilization, including bioinformatic tools utilized in the prediction of co-receptor usage. It also provides novel preliminary analyses for enabling identification of linkages between amino acids in V3 with other components of the HIV-1 genome and demonstrates that these linkages are different between X4 and R5 viruses. PMID:24862329

  19. What Is HIV/AIDS?

    MedlinePlus

    ... Video Games Video Sharing Sites Webcasts/ Webinars Widgets Wikis Follow Us on New Media Virtual Office Hours ... HIV currently exists, but with proper treatment and medical care, HIV can be controlled. The medicine used ...

  20. Research Report: HIV/AIDS

    MedlinePlus

    ... 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. ...

  1. HIV / AIDS: An Unequal Burden

    MedlinePlus

    ... If the person is HIV-negative, then it's critical to review the behaviors that might place him or her at risk. You have to go beyond that and explore the thinking that allows people to conclude that an HIV- ...

  2. HIV/AIDS in Women

    MedlinePlus

    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. ...

  3. Creating a National HIV Curriculum.

    PubMed

    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

  4. Answers about HIV Vaccine Research

    MedlinePlus

    ... a high risk for HIV. However, the heterosexual transmission of HIV is increasingly becoming a major source ... have a major impact on the rates of transmission and help in controlling the epidemic. A partially ...

  5. A case of HIV ulcer

    PubMed Central

    2015-01-01

    HIV-associated ulcers must be distinguished from idiopathic anal fissures in HIV-positive patients and from other sexually transmitted diseases that cause anogenital ulcers as the treatments differ. PMID:26266040

  6. 31 CFR 560.322 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... name of the Government of Iran, any Iranian financial institution, or any other person whose property and interests in property are blocked pursuant to § 560.211, or in which the Government of Iran,...

  7. 31 CFR 560.322 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... name of the Government of Iran, any Iranian financial institution, or any other person whose property and interests in property are blocked pursuant to § 560.211, or in which the Government of Iran,...

  8. Fluvial entrainment of low density peat blocks (block carbon)

    NASA Astrophysics Data System (ADS)

    Warburton, Jeff

    2014-05-01

    In many fluvial environments low density materials are transported in significant quantities and these form an important part of the stream load and /or have a distinct impact on sedimentation in these environments. However, there are significant gaps in understanding of how these materials are entrained and transported by streams and rivers. Eroding upland peatland environments in particular, frequently have fluvial systems in which large eroded peat blocks, often exceeding 1 m in length; form an important component of the stream material flux. Transport of this material is significant in determining rates of erosion but also has important impacts in terms of damage to infrastructure and carbon loss. This paper describes a field experiment designed to establish for the first time the conditions under which large peat blocks (c. > 0.1 m b axis) are initially entrained from a rough gravel bed. The field site is Trout Beck, in the North Pennines, Northern England which is an upland wandering river channel with occasional lateral and mid channel bars. Mean low flow stage is typically 0.2 m but during flood can rapidly rise, in one to two hours, to over 1.5 m. To study peat block entrainment a bespoke data acquisition system consisting of two pressure transducers, four release triggers and time lapse camera was set up. The pressure transducers provided a record of local depth and the release triggers were embedded in peat blocks to record initial motion and arranged on the rough stream bed. The time lapse camera provided verification of timing of block entrainment (during daylight hours) and also provided information on the mechanism of initial movement. Peat blocks were cut from a local source and were equidimensional, ranging in size from 0.1 to 0.7 m. The derived entrainment function is related to a critical depth of entrainment. Results demonstrate that peat blocks are entrained when the local depth approximates the height of the peat block. Blocks frequently shift

  9. Directly Infected Resting CD4+T Cells Can Produce HIV Gag without Spreading Infection in a Model of HIV Latency

    PubMed Central

    Pace, Matthew J.; Graf, Erin H.; Agosto, Luis M.; Mexas, Angela M.; Male, Frances; Brady, Troy; Bushman, Frederic D.; O'Doherty, Una

    2012-01-01

    Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response. PMID:22911005

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

    PubMed Central

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

    2015-01-01

    Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (AnkGAG1D4) and the zinc finger protein (2LTRZFP) have recently been characterized as intracellular antivirals, but these molecules, used individually, do not completely block HIV-1 replication and propagation. The capsid-binder AnkGAG1D4, which inhibits HIV-1 assembly, does not prevent the genome integration of newly incoming viruses. 2LTRZFP, designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1 integration, would have no antiviral effect on HIV-1-infected cells. However, simultaneous expression of these two molecules should combine the advantage of preventive and curative treatments. To test this hypothesis, the genes encoding the N-myristoylated Myr(+)AnkGAG1D4 protein and the 2LTRZFP were introduced into human T-cells, using a third-generation lentiviral vector. SupT1 cells stably expressing 2LTRZFP alone or with Myr(+)AnkGAG1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)AnkGAG1D4 vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral effect. Resistance to viral infection was also observed in primary human CD4+ T-cells stably expressing Myr(+)AnkGAG1D4, and challenged with HIV-1, SIVmac, or SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are promising antiviral agents for anti-HIV-1 gene therapy. PMID:26305555

  11. Treatments for HIV/AIDS

    MedlinePlus

    ... AIDS HIV medicines are giving women longer, healthier futures and new strength. While there's no cure for HIV, the treatments today allow women to live longer, fuller lives. The U.S. Food and Drug Administration (FDA) has approved many drugs for treating HIV. ...

  12. Clinical performance of the Multispot HIV-1/HIV-2 rapid test to correctly differentiate HIV-2 from HIV-1 infection in screening algorithms using third and fourth generation assays and to identify cross reactivity with the HIV-1 Western Blot

    PubMed Central

    Ramos, Eric M.; Harb, Socorro; Dragavon, Joan; Coombs, Robert W.

    2014-01-01

    Background An accurate and rapid serologic method to differentiate HIV-2 from HIV-1 infection is required since the confirmatory HIV-1 Western Blot (WB) may demonstrate cross-reactivity with HIV-2 antibodies. Objectives To evaluate the performance of the Bio-Rad Multispot HIV-1/HIV-2 rapid assay as a supplemental test to correctly identify HIV-2 infection and identify HIV-1 WB cross-reactivity with HIV-2 in clinical samples tested at an academic medical center. Study design Between August 2008 and July 2012, clinical samples were screened for HIV using either 3rd-or 4th-generation HIV-1/2 antibody or combination antibody and HIV-1 p24 antigen assays, respectively. All repeatedly reactive samples were reflexed for Multispot rapid testing. Multispot HIV-2 and HIV-1 and HIV-2-reactive samples were further tested using an HIV-2 immunoblot assay and HIV-1 or HIV-2 RNA assays when possible. The HIV-1 WB was performed routinely for additional confirmation and to assess for HIV-2 antibody cross-reactivity. Results Of 46,061 samples screened, 890 (89.6%) of 993 repeatedly reactive samples were also Multispot-reactive: 882 for HIV-1; three for only HIV-2; and five for both HIV-1 and HIV-2. All three HIV-2-only Multispot-positives along with a single dually reactive HIV-1/2 Multispot-positive were also HIV-2 immunoblot-positive; the latter was HIV-1 RNA negative and HIV-2 RNA positive. Conclusions The Multispot rapid test performed well as a supplemental test for HIV-1/2 diagnostic testing. Four new HIV-2 infections (0.45%) were identified from among 890 Multispot-reactive tests. The use of HIV-1 WB alone to confirm HIV-1/2 screening assays may underestimate the true prevalence of HIV-2 infection in the United States. PMID:24342468

  13. HIV sequence compendium 2002

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Freed, Eric; Hahn, Beatrice; Marx, Preston; McCutchan, Francine; Mellors, John; Wolinsky, Steven; Korber, Bette

    2002-12-31

    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. Traditionally, we present the sequence data themselves in the form of alignments: Section II, an alignment of a selection of HIV-1/SIVcpz full-length genomes (a lot of LAI-like sequences, for example, have been omitted because they are so similar that they bias the alignment); Section III, a combined HIV-1/HIV-2/SIV whole genome alignment; Sections IV–VI, amino acid alignments for HIV-1/SIV-cpz, HIV-2/SIV, and SIVagm. The HIV-2/SIV and SIVagm amino acid alignments are separate because the genetic distances between these groups are so great that presenting them in one alignment would make it very elongated because of the large number of gaps that have to be inserted. As always, tables with extensive background information gathered from the literature accompany the whole genome alignments. The collection of whole-gene sequences in the database is now large enough that we have abundant representation of most subtypes. For many subtypes, and especially for subtype B, a large number of sequences that span entire genes were not included in the printed alignments to conserve space. A more complete version of all alignments is available on our website, http://hiv-web.lanl.gov/content/hiv-db/ALIGN_CURRENT/ALIGN-INDEX.html. Importantly, all these alignments have been edited to include only one sequence per person, based on phylogenetic trees that were created for all of them, as well as on the literature. Because of the number of sequences available, we have decided to use a different selection principle this year, based on the epidemiological importance of the subtypes. Subtypes A–D and CRFs 01 and 02 are by far the most widespread variants, and for these (when available) we have included 8–10 representatives in the alignments. The other

  14. The Building Blocks of Geology.

    ERIC Educational Resources Information Center

    Gibson, Betty O.

    2001-01-01

    Discusses teaching techniques for teaching about rocks, minerals, and the differences between them. Presents a model-building activity that uses plastic building blocks to build crystal and rock models. (YDS)

  15. Carbon-carbon cylinder block

    NASA Technical Reports Server (NTRS)

    Ransone, Philip O. (Inventor)

    1998-01-01

    A lightweight cylinder block composed of carbon-carbon is disclosed. The use of carbon-carbon over conventional materials, such as cast iron or aluminum, reduces the weight of the cylinder block and improves thermal efficiency of the internal combustion reciprocating engine. Due to the negligible coefficient of thermal expansion and unique strength at elevated temperatures of carbon-carbon, the piston-to-cylinder wall clearance can be small, especially when the carbon-carbon cylinder block is used in conjunction with a carbon-carbon piston. Use of the carbon-carbon cylinder block has the effect of reducing the weight of other reciprocating engine components allowing the piston to run at higher speeds and improving specific engine performance.

  16. Standard Missile Block IV battery

    SciTech Connect

    Martin, J.

    1996-11-01

    During the 1980`s a trend in automatic primary battery technologies was the replacement of silver-zinc batteries by thermal battery designs. The Standard missile (SM 2) Block IV development is a noteworthy reversal of this trend. The SM2, Block IV battery was originally attempted as a thermal battery with multiple companies attempting to develop a thermal battery design. These attempts resulted in failure to obtain a production thermal battery. A decision to pursue a silver-zinc battery design resulted in the development of a battery to supply the SM 2, Block IV (thermal battery design goal) and also the projected power requirements of the evolving SM 2, Block IVA in a single silver-zinc battery design. Several advancements in silver-zinc battery technology were utilized in this design that improve the producibility and extend the boundaries of silver-zinc batteries.

  17. Ear - blocked at high altitudes

    MedlinePlus

    ... ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... the middle ear and the back of the nose and upper throat. ... down from high altitudes. Chewing gum the entire time you are ...

  18. Silibinin Inhibits HIV-1 Infection by Reducing Cellular Activation and Proliferation

    PubMed Central

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

    2012-01-01

    Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL), a major component of silymarin, displays anti-HCV effects in humans and also inhibits T-cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+ cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4 and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest that SIL attenuated cellular functions involved in T-cell activation, proliferation, and HIV-1 infection. Silymarin-derived compounds provide cytoprotection by suppressing virus infection, immune activation, and inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV co-infected subjects. PMID:22848626

  19. Microbicides for HIV prevention

    PubMed Central

    Ramjee, Gita

    2011-01-01

    Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV-specific compounds such as surfactants and polyanionic entry inhibitors. However, proof of the microbicide concept as a viable prevention strategy was not provided until the CAPRISA 004 trial of a microbicide containing the HIV-specific antiretroviral tenofovir was completed in mid-2010. Confirmation of the proof of concept provided by CAPRISA 004 by at least two major trials will hopefully lead to licensure of the product by 2018. Parallel studies are planned to ascertain the feasibility of implementation of these products in the public sector with subsequent research focussed on appropriate and acceptable methods of delivery of the active ingredient, and to increase adherence through other delivery systems such as vaginal rings. PMID:22310825

  20. HIV Sequence Compendium 2015

    SciTech Connect

    Foley, Brian Thomas; Leitner, Thomas Kenneth; Apetrei, Cristian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette Tina Marie

    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.

  1. Liposomes for HIV prophylaxis

    PubMed Central

    Malavia, Nikita; Zurakowski, David; Schroeder, Avi; Princiotto, Amy; Laury, Anna Ray; Epstein-Barash, Hila; Sodroski, Joseph; Langer, Robert; Madani, Navid; Kohane, Daniel S.

    2012-01-01

    There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intravaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intravaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women. PMID:21862123

  2. HIV in Southeast Asia.

    PubMed

    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

  3. Modulation of HIV Binding to Epithelial Cells and HIV Transfer from Immature Dendritic Cells to CD4 T Lymphocytes by Human Lactoferrin and its Major Exposed LF-33 Peptide

    PubMed Central

    Carthagena, Laetitia; Becquart, Pierre; Hocini, Hakim; Kazatchkine, Michel D; Bouhlal, Hicham; Belec, Laurent

    2011-01-01

    Lactoferrin (LF), a multifunctional molecule present in human secretions, has potent inhibitory activities against human immunodeficiency virus (HIV). The aim of the study was to evaluate whether human LF (hLF) and its exposed domain LF-33 represented by the peptide (LF-33-GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGP) involved in LF-HIV gag binding and endotoxines neutralization, may inhibit early steps of HIV mucosal transmission. Human LF and the peptide LF-33 inhibited the attachment of primary X4-tropic HIV-1NDK and R5-tropic HIV-1JR-CSF strains to human endometrial (HEC-1) and colorectal (HT-29) CD4-negative epithelial cells, the purified hLF being more potent (up to 80%) than the LF-33 peptide. In addition, the hLF, but not the LF-33 peptide, inhibited up to 40% the transfer in trans of HIV-1JR-CSF and HIV-1NDK, from immature dendritic cells to CD4 T lymphocytes, likely in a DC-SIGN-dependent manner. Altogether, these findings demonstrate that hLF can interfere with HIV-1 mucosal transmission by blocking virus attachment to epithelial cells and by inhibiting virus transfer from dendritic cells to CD4 T cells, two crucial steps of HIV dissemination from mucosae to lymphoid tissue. PMID:21660187

  4. Two Case Studies in the Scientific Method: Antisense Experiments and HIV Vaccination Studies.

    ERIC Educational Resources Information Center

    Guilfoile, Patrick

    1999-01-01

    Presents two recent cases that can be used in the classroom to illustrate the application of scientific methods in biological research: (1) the use of a complementary RNA or DNA molecule to block the production or translation of an mRNA molecule; and (2) the development of HIV trial vaccines. Contains 20 references. (WRM)

  5. 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

    PubMed Central

    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

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

    PubMed Central

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

    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 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, TRIM5αrh RING domain variants also prevented the degradation of TRIM5αrh 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 TRIM5αrh blocks HIV-1 reverse transcription by inducing premature viral uncoating in target cells. PMID:22114335

  7. RING domain mutations uncouple TRIM5α restriction of HIV-1 from inhibition of reverse transcription and acceleration of uncoating.

    PubMed

    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

  8. Skin delivery by block copolymer nanoparticles (block copolymer micelles).

    PubMed

    Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Valour, Jean-Pierre; Rovère, Marie-Rose; Smatti, Batoule; Chevalier, Yves

    2015-12-30

    Block copolymer nanoparticles often referred to as "block copolymer micelles" have been assessed as carriers for skin delivery of hydrophobic drugs. Such carriers are based on organic biocompatible and biodegradable materials loaded with hydrophobic drugs: poly(lactide)-block-poly(ethylene glycol) copolymer (PLA-b-PEG) nanoparticles that have a solid hydrophobic core made of glassy poly(d,l-lactide), and poly(caprolactone)-block-poly(ethylene glycol) copolymer (PCL-b-PEG) nanoparticles having a liquid core of polycaprolactone. In vitro skin absorption of all-trans retinol showed a large accumulation of retinol in stratum corneum from both block copolymer nanoparticles, higher by a factor 20 than Polysorbate 80 surfactant micelles and by a factor 80 than oil solution. Additionally, skin absorption from PLA-b-PEG nanoparticles was higher by one order of magnitude than PCL-b-PEG, although their sizes (65nm) and external surface (water-swollen PEG layer) were identical as revealed by detailed structural characterizations. Fluorescence microscopy of histological skin sections provided a non-destructive picture of the storage of Nile Red inside stratum corneum, epidermis and dermis. Though particle cores had a different physical states (solid or liquid as measured by (1)H NMR), the ability of nanoparticles for solubilization of the drug assessed from their Hildebrand solubility parameters appeared the parameter of best relevance regarding skin absorption. PMID:26602293

  9. Revisiting HIV-1 uncoating.

    PubMed

    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

  10. HIV/AIDS Clinical Trials Fact Sheet

    MedlinePlus

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

  11. Advancing Biosocial Pedagogy for HIV Education

    ERIC Educational Resources Information Center

    Davis, Mark David McGregor

    2011-01-01

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

  12. [Immunopathogenesis of HIV infection].

    PubMed

    Alcamí, José; Coiras, Mayte

    2011-03-01

    Killing of CD4 lymphocytes and systemic immune suppression are the hallmarks of HIV infection. These milestones are produced by different mechanisms that draw a complex picture of AIDS immunopathogenesis. The role of the GALT system as a preferential target for HIV, chronic activation of the immune system and viral escape mechanisms are recent challenges that have changed our current view on the mechanisms leading to immune destruction and development of AIDS. In this article, the mechanisms of immune suppression, the evolution of immune response throughout the infection and the mechanisms of viral escape are analysed. PMID:21388715

  13. HIV: A Chronic Condition.

    PubMed

    Zimmerman, Daniel D

    2015-01-01

    By virtue of the success of anti-retroviral therapy (ART), human immunodeficiency virus (HIV) infection has evolved into a chronic disease in which the typical complications of acquired immune deficiency syndrome (AIDS) are no longer the dominant problem. Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that, in the absence of a cure, will persist for many decades. (1) This review will focus on the longer term sequelae and consequences of chronic HIV infection. PMID:27584920

  14. A mathematical model and CD4+ lymphocyte dynamics in HIV infection.

    PubMed Central

    Hraba, T.; Dolezal, J.

    1996-01-01

    The paper presents a model of CD4 + lymphocyte dynamics in HIV-infected persons. The model incorporates a feedback mechanism regulating the production of T lymphocytes and simulates the dynamics of CD8 + lymphocytes, whose production is assumed to be closely linked to that of CD4 + cells. Because CD4 + lymphocyte counts are a good prognostic indicator of HIV infection, the model was used to simulate such therapeutic interventions as chemotherapy and active and passive immunization. The model also simulated the therapeutic administration of anti-CD8 antibodies; this intervention was assumed to activate T-cell production by activating a feedback mechanism blocked by the high numbers of CD8 + lymphocytes present in HIV-infected persons. The character and implications of the model are discussed in the context of other mathematical models used in HIV infection. PMID:8969246

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    2011-01-01

    Natural antibodies constitute a first-line of defence against pathogens; they may also play other roles in immune regulation and homeostasis, through their ability to bind host antigens, surface molecules and receptors. Natural anti-CCR5 antibodies can be decisive in preventing HIV infection in mucosal tissues and offer prompt and effective protection just at major sites of virus entry. Among natural anti-CCR5 antibodies, IgG and IgA to the ECL1 domain have been shown to block HIV effectively and durably without causing harm to the host. Their biological properties and their uncommon generation in subsets of HIV-infected and HIV-exposed individuals (so called ESN) will be introduced and discussed, with the aim at exploiting their potential in therapy and prevention. PMID:21284903

  17. Importance of an Early HIV Antibody Differentiation Immunoassay for Detection of Dual Infection with HIV-1 and HIV-2

    PubMed Central

    Zbinden, Andrea; Dürig, Roland; Shah, Cyril; Böni, Jürg; Schüpbach, Jörg

    2016-01-01

    Background HIV-2 is primarily endemic in West Africa and India, however, in time of global migration, a possible HIV-2 infection or co-infection with HIV-1 should be recognized right at the time of HIV diagnosis, in order to enable optimized antiretroviral treatment. Laboratory HIV testing consists of a combined HIV1/2/O antibody + antigen screening test and subsequent confirmation and type differentiation by a serological test formatted as a multi-line or multi-spot assay. CDC has proposed a revised alternative HIV diagnostic strategy which, in case of a reactive result in a combined HIV1/2/O antibody + antigen screening test, comprises an HIV-1 nucleic acid test (NAT) for HIV confirmation instead of an antibody differentiation immunoassay (ADI). Only a negative NAT must be further investigated by an ADI, thus saving expenses for ADI in most instances. We have investigated this alternative strategy with respect to its recognition of dual HIV-1 and HIV-2 infection. Methods and Results Anonymized data of HIV notifications of patients newly diagnosed with HIV in Switzerland between 2007 and 2014 were analysed retrospectively. In a total of 4'679 notifications, we found 35 HIV-2 infections, 9 (25.7%) of which were dually infected with HIV-1. In 7 of the 9 dual HIV-1 and HIV-2 infections, HIV-1 RNA testing at the time of HIV diagnosis was positive with concentrations from 102 to 94'300 copies/mL plasma. HIV-1 RNA data were not available for the other two cases. Conclusions The alternative CDC strategy would have missed the concomitant HIV-2 infection in at least 7, but probably even more, of the 9 dually infected patients, as the detectable HIV-1 RNA would have precluded a supplemental ADI. Early ADI is mandatory for diagnosis of dual HIV-1/HIV-2 infection and guidance of appropriate therapy. PMID:27310138

  18. Experiences of HIV Positive Mothers From Rural South India during Intra-Natal Period

    PubMed Central

    Subramaniyan, Anbarasi; Sarkar, Sonali; Roy, Gautam; Lakshminarayanan, Subitha

    2013-01-01

    Context: Tamil Nadu comes under group I high prevalence state, with less than 1% prevalence of HIV infection in antenatal women but above 5% prevalence in high risk group. One of the ways to control HIV/AIDS in India is through Prevention of Parent to Child Transmission (PPTCT), the success of which lies in identifying pregnant women with HIV infection. But due to the stigma against HIV/AIDS among health care providers, HIV positive patients face discrimination in the health sector. Aims: To explore the difficulties faced by rural HIV positive mothers during the intra-natal period. Methods: A descriptive qualitative study was conducted among HIV positive mothers, in Gingee block of Villupuram district, Tamil Nadu, India. All the mothers who tested positive between June 2006 and May 2010 were interviewed in-depth using an interview guide. Results: There were 21 HIV positive mothers during this period, 19 of whom gave consent. Majority of the mothers were <30 years of age from families belonging to lower socio-economic class. The discriminations faced from the health staff was avoidance of physical examination, rude behaviour like throwing of records on the face, discriminatory comments, unnecessary referrals and even refusal to provide intra-partum services. The negative attitude of the staff made a few mothers to deliver in some other institution without disclosing their HIV status. Conclusion: Stigma among health care providers towards HIV positive pregnant women acts as a barrier for improving access to PPTCT services in India and it poses high risk to the mothers, babies and also the health care providers. There is a pressing need to improve access to quality PPTCT services especially during the intranatal period. PMID:24298476

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

    The northwest border city of Tijuana is Mexico's fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006-2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p=0.001). HIV cases at baseline (n=47) most strongly clustered by drug injection sites (Z-Score -6.173; p < 0.001), with a 16 km(2) hotspot near the Mexico/U.S. border, encompassing the red-light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July-December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs. PMID:23606753

  1. HIV peripheral neuropathy.

    PubMed

    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

  2. Development of HIV vectors for anti-HIV gene therapy.

    PubMed Central

    Poeschla, E; Corbeau, P; Wong-Staal, F

    1996-01-01

    Current gene therapy protocols for HIV infection use transfection or murine retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+ progenitor cells ex vivo, followed by infusion of the gene altered cells into autologous or syngeneic/allogeneic recipients. While these studies are essential for safety and feasibility testing, several limitations remain: long-term reconstitution of the immune system is not effected for lack of access to the macrophage reservoir or the pluripotent stem cell population, which is usually quiescent, and ex vivo manipulation of the target cells will be too expensive and impractical for global application. In these regards, the lentivirus-specific biologic properties of the HIVs, which underlie their pathogenetic mechanisms, are also advantageous as vectors for gene therapy. The ability of HIV to specifically target CD4+ cells, as well as non-cycling cells, makes it a promising candidate for in vivo gene transfer vector on one hand, and for transduction of non-cycling stem cells on the other. Here we report the use of replication-defective vectors and stable vector packaging cell lines derived from both HIV-1 and HIV-2. Both HIV envelopes and vesicular stomatitis virus glycoprotein G were effective in mediating high-titer gene transfer, and an HIV-2 vector could be cross-packaged by HIV-1. Both HIV-1 and HIV-2 vectors were able to transduce primary human macrophages, a property not shared by murine retroviruses. Vesicular stomatitis virus glycoprotein G-pseudotyped HIV vectors have the potential to mediate gene transfer into non-cycling hematopoietic stem cells. If so, HIV or other lentivirus-based vectors will have applications beyond HIV infection. Images Fig. 1 PMID:8876146

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

    SciTech Connect

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie . E-mail: v.bosch@dkfz.de

    2007-05-10

    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-Env767{sup stop}, which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752{sup N750K}) 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-Tr752{sup N750K} 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.

  4. A standardized block fabrication technique

    SciTech Connect

    Famiglietti, R.; Noriega, B.; Sanders, R. )

    1990-01-01

    The accuracy of delivered dose is a primary goal in every radiation therapy department. Improved imaging techniques now enable the radiation therapist to define more precisely the area of interest, which helps the sparing of normal surrounding tissue. Tray-mounted customized blocks are routinely used to define this treatment portal accurately and reproducibly. However, the level of accuracy is dependent on the block fabrication technique and the skill of the block cutter. We at Moffitt Cancer Center have standardized our system in a way that minimizes some of the human errors, while keeping the procedure fast and accurate. This system uses a tray template that simulates our blocking trays. The function of this tray is to position the styrofoam (and therefore the cerrobend block) on the tray in such a way as to insure proper alignment with the treatment machine. We also feel this improves upon some common designs using random holes or hole patterns, which may interfere with the treatment area. This system is not overly sophisticated and can be easily implemented in most radiation therapy departments.

  5. Block Matching for Object Tracking

    SciTech Connect

    Gyaourova, A; Kamath, C; Cheung, S

    2003-10-13

    Models which describe road traffic patterns can be helpful in detection and/or prevention of uncommon and dangerous situations. Such models can be built by the use of motion detection algorithms applied to video data. Block matching is a standard technique for encoding motion in video compression algorithms. We explored the capabilities of the block matching algorithm when applied for object tracking. The goal of our experiments is two-fold: (1) to explore the abilities of the block matching algorithm on low resolution and low frame rate video and (2) to improve the motion detection performance by the use of different search techniques during the process of block matching. Our experiments showed that the block matching algorithm yields good object tracking results and can be used with high success on low resolution and low frame rate video data. We observed that different searching methods have small effect on the final results. In addition, we proposed a technique based on frame history, which successfully overcame false motion caused by small camera movements.

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

    PubMed

    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

  7. APOBEC3G Inhibits HIV-1 RNA Elongation by Inactivating the Viral Trans-Activation Response Element

    PubMed Central

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

    2014-01-01

    Deamination of cytidine residues in viral DNA (vDNA) is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient 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 defence 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. Finally, we show that free 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, identifying A3G as an efficient mutator, and that deamination of (−)SSDNA results in an early block of HIV-1 transcription. PMID:24859335

  8. A beta-galactose-specific lectin isolated from the marine worm Chaetopterus variopedatus possesses anti-HIV-1 activity.

    PubMed

    Wang, Jian-Hua; Kong, Jing; Li, Wei; Molchanova, Valentina; Chikalovets, Irina; Belogortseva, Natalia; Luk'yanov, Pavel; Zheng, Yong-Tang

    2006-01-01

    A 30 kDa beta-galactose-specific lectin named CVL was isolated from the polychaete marine worm Chaetopterus variopedatus (Annelida) and its anti-HIV-1 activity in vitro was determined. Results showed that CVL inhibited cytopathic effect induced by HIV-1 and the production of viral p24 antigen. The EC(50) values were 0.0043 and 0.057 microM, respectively. Time-of-addition analysis of anti-HIV-1 activity indicated its action was at the early stage of virus replication. CVL could blocked the cell-to-cell fusion process of HIV infected and uninfected cells with an EC(50) of 0.073 microM. The inhibition of HIV-1 entry into host cells was demonstrated by using fluorescence-based real-time quantify PCR. At CVL concentration of 0.33 microM and 0.07 microM, 86% and 21% virus attachment were blocked, respectively. The anti-HIV-1 action of CVL might relate to blockade of HIV-1 entry into cells. PMID:16316787

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

    PubMed

    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

    2015-09-21

    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. PMID:26274532

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Uwah, Chijioke

    2014-01-01

    The need to effectively communicate HIV/AIDS messages in South Africa, given the high prevalence of the pandemic, cannot be overemphasised. Communication scholars have long emphasised the need to recognise adherence to cultural norms of target communities as catalyst for effective HIV/AIDS communication. Unfortunately this call has not been totally heeded by the designers of HIV/AIDS communication instruments. In the case of theatre, research has shown that in South Africa, theatre groups have gone into communities with pre-packaged plays without due cognisance of the cultural norms and beliefs of the target population. This research was conducted in KwaZulu-Natal (the province with the highest prevalence rate of HIV/AIDS infection in South Africa). Using a qualitative research methodology this paper investigated the inclusion/non-inclusion of the cultural norms of the target population in the design of the dramatic performance by the theatre group in its HIV/AIDS campaigns. The findings indicate that while the group did try to incorporate aspects of the cultural norms of the target population, it did so at a level that failed to effectively communicate the HIV/AIDS message to its audiences. This paper therefore seeks to show through empirical evidence that the non-inclusion of cultural norms and values of the target population has acted as a stumbling block in the effective communication of HIV/AIDS messages by theatre groups in the country. PMID:24697309

  12. Differential Effects of Tra2ß Isoforms on HIV-1 RNA Processing and Expression

    PubMed Central

    Platt, Craig; Calimano, Maria; Nemet, Josip; Bubenik, Jodi; Cochrane, Alan

    2015-01-01

    Balanced processing of HIV-1 RNA is critical to virus replication and is regulated by host factors. In this report, we demonstrate that overexpression of either Tra2α or Tra2β results in a marked reduction in HIV-1 Gag/ Env expression, an effect associated with changes in HIV-1 RNA accumulation, altered viral splice site usage, and a block to export of HIV-1 genomic RNA. A natural isoform of Tra2β (Tra2ß3), lacking the N-terminal RS domain, also suppressed HIV-1 expression but had different effects on viral RNA processing. The functional differences between the Tra2β isoforms were also observed in the context of another RNA substrate indicating that these factors have distinct functions within the cell. Finally, we demonstrate that Tra2ß depletion results in a selective reduction in HIV-1 Env expression as well as an increase in multiply spliced viral RNA. Together, the findings indicate that Tra2α/β can play important roles in regulating HIV-1 RNA metabolism and expression. PMID:25970345

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

    PubMed

    Uwah, Chijioke

    2013-01-01

    The need to effectively communicate HIV/AIDS messages in South Africa, given the high prevalence of the pandemic, cannot be overemphasised. Communication scholars have long emphasised the need to recognise adherence to cultural norms of target communities as catalyst for effective HIV/AIDS communication. Unfortunately this call has not been totally heeded by the designers of HIV/AIDS communication instruments. In the case of theatre, research has shown that in South Africa, theatre groups have gone into communities with pre-packaged plays without due cognisance of the cultural norms and beliefs of the target population. This research was conducted in KwaZulu-Natal (the province with the highest prevalence rate of HIV/AIDS infection in South Africa). Using a qualitative research methodology this paper investigated the inclusion/non-inclusion of the cultural norms of the target population in the design of the dramatic performance by the theatre group in its HIV/AIDS campaigns. The findings indicate that while the group did try to incorporate aspects of the cultural norms of the target population, it did so at a level that failed to effectively communicate the HIV/AIDS message to its audiences. This paper therefore seeks to show through empirical evidence that the non-inclusion of cultural norms and values of the target population has acted as a stumbling block in the effective communication of HIV/AIDS messages by theatre groups in the country. PMID:24697309

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

    PubMed Central

    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

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

    PubMed

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

  16. Synthesis of a Vpr-Binding Derivative for Use as a Novel HIV-1 Inhibitor

    PubMed Central

    Hagiwara, Kyoji; Ishii, Hideki; Murakami, Tomoyuki; Takeshima, Shin-nosuke; Chutiwitoonchai, Nopporn; Kodama, Eiichi N.; Kawaji, Kumi; Kondoh, Yasumitsu; Honda, Kaori; Osada, Hiroyuki; Tsunetsugu-Yokota, Yasuko; Suzuki, Masaaki; Aida, Yoko

    2015-01-01

    The emergence of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus type 1 (HIV-1) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. We previously identified a potential parent compound, hematoxylin, which suppresses the nuclear import of HIV-1 via the Vpr-importin α interaction and inhibits HIV-1 replication in a Vpr-dependent manner by blocking nuclear import of the pre-integration complex. However, it was unstable. Here, we synthesized a stable derivative of hematoxylin that bound specifically and stably to Vpr and inhibited HIV-1 replication in macrophages. Furthermore, like hematoxylin, the derivative inhibited nuclear import of Vpr in an in vitro nuclear import assay, but had no effect on Vpr-induced G2/M phase cell cycle arrest or caspase activity. Interestingly, this derivative bound strongly to amino acid residues 54–74 within the C-terminal α-helical domain (αH3) of Vpr. These residues are highly conserved among different HIV strains, indicating that this region is a potential target for drug-resistant HIV-1 infection. Thus, we succeeded in developing a stable hematoxylin derivative that bound directly to Vpr, suggesting that specific inhibitors of the interaction between cells and viral accessory proteins may provide a new strategy for the treatment of HIV-1 infection. PMID:26701275

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

    PubMed

    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

  18. Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells

    PubMed Central

    Lassen, Kara G; Ramyar, Kasra X; Bailey, Justin R; Zhou, Yan; Siliciano, Robert F

    2006-01-01

    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. PMID:16839202

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

    NASA Technical Reports Server (NTRS)

    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.

  20. SAMHD1 Limits HIV-1 Antigen Presentation by Monocyte-Derived Dendritic Cells

    PubMed Central

    Bruel, Timothée; Cardinaud, Sylvain; Porrot, Françoise; Prado, Julia G.; Moris, Arnaud

    2015-01-01

    ABSTRACT Monocyte-derived dendritic cells (MDDC) stimulate CD8+ cytotoxic T lymphocytes (CTL) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class I (MHC-I) molecules. MDDC are poorly susceptible to HIV-1, in part due to the presence of SAMHD1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dNTPs) and degrades viral RNA. Vpx, an HIV-2/SIVsm protein absent from HIV-1, antagonizes SAMHD1 by inducing its degradation. The impact of SAMHD1 on the adaptive cellular immune response remains poorly characterized. Here, we asked whether SAMHD1 modulates MHC-I-restricted HIV-1 antigen presentation. Untreated MDDC or MDDC pretreated with Vpx were exposed to HIV-1, and antigen presentation was examined by monitoring the activation of an HIV-1 Gag-specific CTL clone. SAMHD1 depletion strongly enhanced productive infection of MDDC as well as endogenous HIV-1 antigen presentation. Time-lapse microscopy analysis demonstrated that in the absence of SAMHD1, the CTL rapidly killed infected MDDC. We also report that various transmitted/founder (T/F) HIV-1 strains poorly infected MDDC and, as a consequence, did not stimulate CTL. Vesicular stomatitis virus glycoprotein (VSV-G) pseudotyping of T/F alleviated a block in viral entry and induced antigen presentation only in the absence of SAMHD1. Furthermore, by using another CTL clone that mostly recognizes incoming HIV-1 antigens, we demonstrate that SAMHD1 does not influence exogenous viral antigen presentation. Altogether, our results demonstrate that the antiviral activity of SAMHD1 impacts antigen presentation by DC, highlighting the link that exists between restriction factors and adaptive immune responses. IMPORTANCE Upon viral infection, DC may present antigens derived from incoming viral material in the absence of productive infection of DC or from newly synthesized viral proteins. In the case of HIV, productive infection of DC is blocked at an early

  1. A New Approach to Produce HIV-1 Envelope Trimers

    PubMed Central

    AlSalmi, Wadad; Mahalingam, Marthandan; Ananthaswamy, Neeti; Hamlin, Christopher; Flores, Dalia; Gao, Guofen; Rao, Venigalla B.

    2015-01-01

    The trimeric envelope spike of HIV-1 mediates virus entry into human cells. The exposed part of the trimer, gp140, consists of two noncovalently associated subunits, gp120 and gp41 ectodomain. A recombinant vaccine that mimics the native trimer might elicit entry-blocking antibodies and prevent virus infection. However, preparation of authentic HIV-1 trimers has been challenging. Recently, an affinity column containing the broadly neutralizing antibody 2G12 has been used to capture recombinant gp140 and prepare trimers from clade A BG505 that naturally produces stable trimers. However, this antibody-based approach may not be as effective for the diverse HIV-1 strains with different epitope signatures. Here, we report a new and simple approach to produce HIV-1 envelope trimers. The C terminus of gp140 was attached to Strep-tag II with a long linker separating the tag from the massive trimer base and glycan shield. This allowed capture of nearly homogeneous gp140 directly from the culture medium. Cleaved, uncleaved, and fully or partially glycosylated trimers from different clade viruses were produced. Extensive biochemical characterizations showed that cleavage of gp140 was not essential for trimerization, but it triggered a conformational change that channels trimers into correct glycosylation pathways, generating compact three-blade propeller-shaped trimers. Uncleaved trimers entered aberrant pathways, resulting in hyperglycosylation, nonspecific cross-linking, and conformational heterogeneity. Even the cleaved trimers showed microheterogeneity in gp41 glycosylation. These studies established a broadly applicable HIV-1 trimer production system as well as generating new insights into their assembly and maturation that collectively bear on the HIV-1 vaccine design. PMID:26088135

  2. Toy Blocks and Rotational Physics

    NASA Astrophysics Data System (ADS)

    Varieschi, Gabriele U.; Jully, Isabel R.

    2005-09-01

    Have you ever observed a child playing with toy blocks? A favorite game is to build towers and then make them topple like falling trees. To the eye of a trained physicist this should immediately look like an example of the physics of "falling chimneys," when tall structures bend and break in mid-air while falling to the ground. The game played with toy blocks can actually reproduce well what is usually seen in photographs of falling towers, such as the one that appeared on the cover of the September 1976 issue of The Physics Teacher. In this paper we describe how we performed and analyzed these simple but interesting experiments with toy blocks.

  3. Projectors, shadows, and conformal blocks

    NASA Astrophysics Data System (ADS)

    Simmons-Duffin, David

    2014-04-01

    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" 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.

  4. Pseudophakic pupillary-block glaucoma.

    PubMed Central

    Werner, D.; Kaback, M.

    1977-01-01

    Four cases of iris-supported pseudophakic pupillary-block glaucoma were presented. Pupillary-block glaucoma is the first postoperative complication seen following the implantation of an intraocular lens, and in our series occurred at an incidence of 3-8%. A short review was made of pupillary-block glaucoma with all types of intraocular lenses, with emphasis on the iris-supported lens. The role of inflammation, haemorrhage, and vitreous and lens material in obstructing aqueous flow at the pupil and peripheral iridectomy site was emphasised. Pitfalls in the diagnosis and management of this condition were reviewed. Methods of prevention and treatment were reviewed with emphasis on early mydriasis, along with carbonic anhydrase inhibitors and hyperosmotic agents as a primary medical treatment. Iridectomy, laser iridotomy, or transfixation of the iris was mentioned as a surgical treatment. PMID:871462

  5. Block-based neural networks.

    PubMed

    Moon, S W; Kong, S G

    2001-01-01

    This paper presents a novel block-based neural network (BBNN) model and the optimization of its structure and weights based on a genetic algorithm. The architecture of the BBNN consists of a 2D array of fundamental blocks with four variable input/output nodes and connection weights. Each block can have one of four different internal configurations depending on the structure settings, The BBNN model includes some restrictions such as 2D array and integer weights in order to allow easier implementation with reconfigurable hardware such as field programmable logic arrays (FPGA). The structure and weights of the BBNN are encoded with bit strings which correspond to the configuration bits of FPGA. The configuration bits are optimized globally using a genetic algorithm with 2D encoding and modified genetic operators. Simulations show that the optimized BBNN can solve engineering problems such as pattern classification and mobile robot control. PMID:18244385

  6. Tharsis block tectonics on Mars

    NASA Technical Reports Server (NTRS)

    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.

  7. Automatic blocking of nested loops

    NASA Technical Reports Server (NTRS)

    Schreiber, Robert; Dongarra, Jack J.

    1990-01-01

    Blocked algorithms have much better properties of data locality and therefore can be much more efficient than ordinary algorithms when a memory hierarchy is involved. On the other hand, they are very difficult to write and to tune for particular machines. The reorganization is considered of nested loops through the use of known program transformations in order to create blocked algorithms automatically. The program transformations used are strip mining, loop interchange, and a variant of loop skewing in which invertible linear transformations (with integer coordinates) of the loop indices are allowed. Some problems are solved concerning the optimal application of these transformations. It is shown, in a very general setting, how to choose a nearly optimal set of transformed indices. It is then shown, in one particular but rather frequently occurring situation, how to choose an optimal set of block sizes.

  8. HIV and development.

    PubMed

    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

  9. Women, drugs and HIV

    PubMed Central

    Azim, Tasnim; Bontell, Irene; Strathdee, Steffanie A.

    2014-01-01

    Women who inject drugs are among the most vulnerable to HIV through both unsafe injections and unprotected sex. They are also among the most hidden affected populations, as they are more stigmatized than their male counterparts. Many sell sex to finance their own and their partner’s drug habit and often their partner exerts a significant amount of control over their sex work, condom use and injection practices. Women who use drugs all over the world face many different barriers to HIV service access including police harassment, judgmental health personnel and a fear of losing their children. In order to enable these women to access life-saving services including needle-syringe and condom programs, opioid substitution therapy and HIV testing and treatment, it is essential to create a conducive environment and provide tailor-made services that are adapted to their specific needs. In this commentary, we explore the risks and vulnerabilities of women who use drugs as well as the interventions that have been shown to reduce their susceptibility to HIV infection. PMID:25277726

  10. Modeling HIV Cure

    NASA Astrophysics Data System (ADS)

    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.

  11. HIV Excess Cancers JNCI

    Cancer.gov

    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. The Science of HIV.

    ERIC Educational Resources Information Center

    DiSpezio, Michael

    This book is the first curriculum developed to bring cutting edge research on the HIV virus into science classrooms. The book and video are coordinated to provide a range of learning opportunities--labs, activities, readings, model design, guided discussions and, in the video, a way to see research in action. Both the book and video emphasize the…

  13. Block ground interaction of rockfalls

    NASA Astrophysics Data System (ADS)

    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.

  14. China update: HIV increasing.

    PubMed

    Gil, V E

    1993-01-01

    The HIV/AIDS case rate in China increased 117% over the period 1990-1992, from 446 to 957 HIV infections. While the majority of cases in 1990 were localized in Yunnan among minority farmers and manual laborers, infection is now found in 19 provinces, counties, and urban areas over a wider spectrum of society. The concentration of cases among IV-drug users has decreased from 83.4% to 72.6%. HIV monitoring and prevention stations have been in place in the country since 1986. The government also encouraged special zones and semiautonomous cities as well as the World Health Organization to take steps to monitor and prevent the spread of HIV. While these effort have served to augment the degree of sex education previously provided, low budgets, bureaucracy, and ambivalence have impeded control efforts. Only 1.25 million of the 1.16 billion population has been serosampled over 8 years and 100,000 fewer serosamples were taken in 1992 compared to in 1991. Neither the general population nor health workers have sufficient knowledge about HIV/AIDS to prevent its continued spread. While gay men sampled in Beijing were better informed about transmission means and risk groups, over two thirds believed they were not at risk if they avoided having sex with foreigners. Recent economic reform measures allowing large movements of population from rural to urban areas, increased disposable income available for prostitutes, and greater exposure to alternative sexual norms and behaviors through the media and music further increase the risk of HIV transmission, especially among the younger generation. To counter these risks, an AIDS hotline for information and referrals has been established in Beijing which openly reaches out to the homosexual community and fields 8-12 calls/day. Training programs for doctors, counselors, professors, and social workers have been attended by people from more than 30 provinces and regions. In addition, modest research into sexual behavior is also being

  15. Triggering TLR2, -3, -4, -5, and -8 Reinforces the Restrictive Nature of M1- and M2-Polarized Macrophages to HIV

    PubMed Central

    Schlaepfer, Erika; Rochat, Mary-Aude; Duo, Li

    2014-01-01

    ABSTRACT Macrophages must react to a large number of pathogens and their effects. In chronic HIV infection, the microenvironment changes with an influx of microbial products that trigger Toll-like receptors (TLRs). That dynamic nature can be replicated ex vivo by the proinflammatory (M1-polarized) and alternatively activated (M2-polarized) macrophages. Thus, we determined how polarized macrophages primed by various TLR agonists support HIV replication. Triggering of TLR2, -3, -4, -5, and -8 reinforced the low level of permissiveness in polarized macrophages. HIV was inhibited even more in M1-polarized macrophages than in macrophages activated only by TLR agonists. HIV was inhibited before its integration into the host chromosome. Polarization and triggering by various TLR agonists resulted in distinct cytokine profiles, endocytic activity, and distinct upregulation of restriction factors of HIV. Thus, different mechanisms likely contribute to the HIV-inhibitory effects. In chronic HIV infection, macrophages might become less permissive to HIV due to changes in the microenvironment. The high level of reactivity of polarized macrophages to TLR triggering may be exploited for immunotherapeutic strategies. IMPORTANCE Macrophages are a major target of HIV-1 infection. Different cell types in this very heterogeneous cell population respond differently to stimuli. In vitro, the heterogeneity is mimicked by their polarization into proinflammatory and alternatively activated macrophages. Here we explored the extent to which agonists triggering the TLR family affect HIV replication in polarized macrophages. We found that a number of TLR agonists blocked HIV replication substantially when given before infection. We also report the mechanisms of how TLR agonists exert their inhibitory action. Our findings may advance our understanding of which and how TLR agonists block HIV infection in polarized macrophages and may facilitate the design of novel immunotherapeutic approaches

  16. Block LancZos PACKage

    Energy Science and Technology Software Center (ESTSC)

    2005-05-01

    BLZPACK (for Block LancZos PACKage) is a standard Fortran 77 implementation of the block Lanczos algorithm intended for the solution of the standard eigenvalue problem Ax=ux or the generalized eigenvalue problem Ax=uBx, where A and B are real, sparse symmetric matrices, u and eigenvalue and x and eigenvector. The development of this eigensolver was motivated by the need to solve large, sparse, generalized problems from free vibration analyses in structural engineering. Several upgrades were performedmore » afterwards aiming at the solution of eigenvalues problems from a wider range of applications.« less

  17. HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel; Dumaop, Wilmar; Elueteri, Simona; Campos, Sofia; Serger, Elisabeth; Trejo, Margarita; Kosberg, Kori; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; He, Johnny J.

    2015-01-01

    Antiretroviral therapy has increased the life span of HIV+ individuals; however, HIV-associated neurocognitive disorder (HAND) occurrence is increasing in aging HIV patients. Previous studies suggest HIV infection alters autophagy function in the aging CNS and HIV-1 proteins affect autophagy in monocyte-derived cells. Despite these findings, the mechanisms leading to dysregulated autophagy in the CNS remain unclear. Here we sought to determine how HIV Tat dysregulates autophagy in neurons. Tat caused a dose-dependent decrease in autophagosome markers, microtubule-associated protein-1 light chain β II (LC3II), and sequestosome 1(SQSTM1), in a membrane-enriched fraction, suggesting Tat increases autophagic degradation. Bafilomycin A1 increased autophagosome number, LC3II, and SQSTM1 accumulation; Tat cotreatment diminished this effect. Tat had no effect when 3-methyladenine or knockdown of beclin 1 blocked early stages of autophagy. Tat increased numbers of LC3 puncta and resulted in the formation of abnormal autophagosomes in vitro. Likewise, in vivo studies in GFAP-Tat tg mice showed increased autophagosome accumulation in neurons, altered LC3II levels, and neurodegeneration. These effects were reversed by rapamycin treatment. Tat colocalized with autophagosome and lysosomal markers and enhanced the colocalization of autophagosome with lysosome markers. Furthermore, co-IP studies showed that Tat interacts with lysosomal-associated membrane protein 2A (LAMP2A) in vitro and in vivo, and LAMP2A overexpression reduces Tat-induced neurotoxicity. Hence, Tat protein may induce autophagosome and lysosome fusion through interaction with LAMP2A leading to abnormal neuronal autophagy function and dysregulated degradation of critical intracellular components. Therapies targeting Tat-mediated autophagy alterations may decrease neurodegeneration in aging patients with HAND. PMID:25653352

  18. HIV Sequence Compendium 2010

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Leitner, Thomas; Apetrei, Christian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette

    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.

  19. Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59.

    PubMed Central

    Schmitz, J; Zimmer, J P; Kluxen, B; Aries, S; Bögel, M; Gigli, I; Schmitz, H

    1995-01-01

    Various immune mechanisms have been reported to contribute to the progressive destruction of Th cells in HIV-1-infected patients. Among these, complement mediated lysis of infected cells has been suggested. An increased sensitivity of lymphocytes from HIV-1-infected patients to lysis by monoclonal antibodies directed to MHC class I antigen and complement has been directly correlated with a decreased expression of the decay accelerating factor (CD55). It also has been reported that the expression of the membrane inhibitor of reactive lysis (CD59) is decreased during HIV-1 infection. We examined the effect of antibodies in the serum of HIV-1-positive individuals and normal human serum (NHS) as source of complement on several HIV-1-infected cell lines differing in their expression of CD55 and CD59. When HIV-1-infected target cells without membrane expression of CD55 and CD59 were used, a highly significant cytotoxic effect was observed in the presence of heat inactivated anti-HIV-1-positive sera and NHS, while heat-inactivated anti-HIV-1-negative sera and NHS were unable to induce cytolysis. Similar results were obtained using purified IgG isolated from HIV-1-positive sera and either NHS or guinea pig serum as source of complement. Lysis of HIV-1-infected cells correlated with expression of viral antigens on the cell surface. HIV-1-infected CD55 and CD59 positive target cells showed specific lysis, when the function of these molecules was abrogated by blocking antibodies to CD55 and CD59. The finding of anti-HIV-1-specific cytotoxic antibodies in sera from HIV-1-infected patients should be considered in the pathogenesis of the HIV-1-infection. PMID:7544808

  20. Autophagy Restricts HIV-1 Infection by Selectively Degrading Tat in CD4+ T Lymphocytes

    PubMed Central

    Sagnier, Sophie; Daussy, Coralie F.; Borel, Sophie; Robert-Hebmann, Véronique; Faure, Mathias; Blanchet, Fabien P.; Beaumelle, Bruno; Biard-Piechaczyk, Martine

    2014-01-01

    ABSTRACT Autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. Autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. Upon human immunodeficiency virus type 1 (HIV-1) infection, viral envelope (Env) glycoproteins induce autophagy-dependent apoptosis of uninfected bystander CD4+ T lymphocytes, a mechanism likely contributing to the loss of CD4+ T cells. In contrast, in productively infected CD4+ T cells, HIV-1 is able to block Env-induced autophagy in order to avoid its antiviral effect. To date, nothing is known about how autophagy restricts HIV-1 infection in CD4+ T lymphocytes. Here, we report that autophagy selectively degrades the HIV-1 transactivator Tat, a protein essential for viral transcription and virion production. We demonstrated that this selective autophagy-mediated degradation of Tat relies on its ubiquitin-independent interaction with the p62/SQSTM1 adaptor. Taken together, our results provide evidence that the anti-HIV effect of autophagy is specifically due to the degradation of the viral transactivator Tat but that this process is rapidly counteracted by the virus to favor its replication and spread. IMPORTANCE Autophagy is recognized as one of the most ancient and conserved mechanisms of cellular defense against invading pathogens. Cross talk between HIV-1 and autophagy has been demonstrated depending on the virally challenged cell type, and HIV-1 has evolved strategies to block this process to replicate efficiently. However, the mechanisms by which autophagy restricts HIV-1 infection remain to be elucidated. Here, we report that the HIV-1 transactivator Tat, a protein essential for viral replication, is specifically degraded by autophagy in CD4+ T lymphocytes

  1. A molecular tweezer antagonizes seminal amyloids and HIV infection

    PubMed Central

    Lump, Edina; Castellano, Laura M; Meier, Christoph; Seeliger, Janine; Erwin, Nelli; Sperlich, Benjamin; Stürzel, Christina M; Usmani, Shariq; Hammond, Rebecca M; von Einem, Jens; Gerold, Gisa; Kreppel, Florian; Bravo-Rodriguez, Kenny; Pietschmann, Thomas; Holmes, Veronica M; Palesch, David; Zirafi, Onofrio; Weissman, Drew; Sowislok, Andrea; Wettig, Burkhard; Heid, Christian; Kirchhoff, Frank; Weil, Tanja; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Sanchez-Garcia, Elsa; Winter, Roland; Shorter, James; Münch, Jan

    2015-01-01

    Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses. DOI: http://dx.doi.org/10.7554/eLife.05397.001 PMID:26284498

  2. Harnessing the protective potential of HIV-1 neutralizing antibodies

    PubMed Central

    Smith, S Abigail; Derdeyn, Cynthia A

    2016-01-01

    Recent biological, structural, and technical advances are converging within the HIV-1 vaccine field to harness the power of antibodies for prevention and therapy. Numerous monoclonal antibodies with broad neutralizing activity against diverse HIV-1 isolates have now been identified, revealing at least five sites of vulnerability on the envelope (Env) glycoproteins. While there are practical and technological barriers blocking a clear path from broadly neutralizing antibodies (bNAb) to a protective vaccine, this is not a dead end. Scientists are revisiting old approaches with new technology, cutting new trails through unexplored territory, and paving new roads in the hopes of preventing HIV-1 infection. Other promising avenues to capitalize on the power of bNAbs are also being pursued, such as passive antibody immunotherapy and gene therapy approaches. Moreover, non-neutralizing antibodies have inhibitory activities that could have protective potential, alone or in combination with bNAbs. With a new generation of bNAbs, and a clinical trial that associated antibodies with reduced acquisition, the field is closer than ever to developing strategies to use antibodies against HIV-1. PMID:26918160

  3. Microbial translocation in the pathogenesis of HIV infection and AIDS.

    PubMed

    Marchetti, Giulia; Tincati, Camilla; Silvestri, Guido

    2013-01-01

    In pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species. In vivo studies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4(+) depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Direct in situ evidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS. PMID:23297256

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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

  6. Calibrator Blocks For Computerized Tomography (CT)

    NASA Technical Reports Server (NTRS)

    Engel, H. Peter

    1990-01-01

    Sets of calibrator blocks developed for use with industrial computerized tomography (CT) systems. Set of blocks (or number of stacked sets of blocks) placed on object table of CT system and scanned in usual way. Blocks include holes of known size, shape, and location. Appearance of holes in output image of CT system used to verify operation of system.

  7. Teaching Numeracy, Language, and Literacy with Blocks

    ERIC Educational Resources Information Center

    Newburger, Abigail; Vaughan, Elizabeth

    2006-01-01

    By enhancing the block play in classrooms, teachers can help children acquire the emerging skills they need--with numbers, vocabulary, and reading--for kindergarten readiness. Newburger and Vaughan provide a theoretical foundation describing why and how to use blocks, and give guidance on selecting blocks and block safety. With chapters on the…

  8. Unit Blocks: A Curriculum for Early Learning.

    ERIC Educational Resources Information Center

    Banta, Mary Ann

    Teachers can use unit blocks as tools for directed learning activities, or blocks can be reserved for children's discovery learning experiences. To use unit blocks for discovery learning, children need adequate, protected space and sufficient, uninterrupted time. Given opportunities for free play with unit blocks, children progress through seven…

  9. Block Scheduling's Missteps, Successes and Variables.

    ERIC Educational Resources Information Center

    Rettig, Michael D.; Canady, Robert Lynn

    2003-01-01

    Documents Virginia's history of adoption and implementation of block scheduling, highlights common forms of block scheduling, and describes mistakes that caused schools to abandon block scheduling. Describes three key variables (time, teachers, and students) in the use of block scheduling to improve student achievement. (PKP)

  10. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  11. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  12. HIV and homosexuality in Pakistan.

    PubMed

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

    2008-08-01

    In Pakistan, seven times more men are reported to be infected with HIV than women. Among the Pakistani population, modes of HIV transmission include infection through sexual contact, contaminated blood and blood products, injecting drug use, and mother-to-child transmission. Although most sexual transmission of HIV results from unsafe heterosexual contact, homosexual and bisexual contact also represent important modes of transmission. According to unpublished reports, the prevalence of HIV among homosexual and bisexual Pakistani men is reaching alarming proportions. We describe the Pakistani homosexual and bisexual culture, review statistics regarding HIV prevalence and risk behaviour, and identify areas of improvement in the HIV policy with specific focus on men who have sex with men. PMID:18652997

  13. What is a MISR block?

    Atmospheric Science Data Center

    2016-02-21

    ... and processing of these data, swathes are broken into a series of predefined, uniformly-sized boxes along the ground track called ... about 142 blocks will contain valid data at any particular time. A MISR Browse Tool is available to help determine MISR paths and ...

  14. Building Blocks for Personal Brands

    ERIC Educational Resources Information Center

    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.

  15. Preschoolers' Thinking during Block Play

    ERIC Educational Resources Information Center

    Piccolo, Diana L.; Test, Joan

    2010-01-01

    Children build foundations for mathematical thinking in early play and exploration. During the preschool years, children enjoy exploring mathematical concepts--such as patterns, shape, spatial relationships, and measurement--leading them to spontaneously engage in mathematical thinking during play. Block play is one common example that engages…

  16. The Federal Block Grant Experience.

    ERIC Educational Resources Information Center

    Levy, Seymour; Linster, Charles A.

    Block grants have been defined as programs through which funds are provided to governmental units, such as state or local governments, based upon a statutory formula. They are usually provided for use in a defined, but broad, area and at the recipient's discretion. This document describes the historical development of these grants and the role of…

  17. Kinetic model of HIV infection

    SciTech Connect

    Zhdanov, V. P.

    2007-10-15

    Recent experiments clarifying the details of exhaustion of CD8 T cells specific to various strains of human immunodeficiency virus (HIV) are indicative of slow irreversible (on a one-year time scale) deterioration of the immune system. The conventional models of HIV kinetics do not take this effect into account. Removing this shortcoming, we show the likely influence of such changes on the escape of HIV from control of the immune system.

  18. [Anal cancer in HIV patients].

    PubMed

    Quéro, Laurent; Duval, Xavier; Abramowitz, Laurent

    2014-11-01

    Despite effective highly active antiretroviral treatment, anal cancer incidence has recently strongly increased in HIV-infected population. Treatment strategy in HIV-infected patients does not differ from general population. HIV-infected patients treated by chemo-radiotherapy are exposed to high-grade toxicities and should be closely monitored to deliver the optimal treatment. Close collaboration between oncologist and infectiologist is highly recommended to adjust antiretroviral therapy if necessary. PMID:25418596

  19. HIV testing, staging, and evaluation.

    PubMed

    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

  20. Preventing HIV Infection in Women

    PubMed Central

    Adimora, Adaora A.; Ramirez, Catalina; Auerbach, Judith D.; Aral, Sevgi O.; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth Anne

    2014-01-01

    Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be done in order to implement scientific advancements and to resolve the many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities. PMID:23764631

  1. Immunology of Pediatric HIV Infection

    PubMed Central

    Tobin, Nicole H.; Aldrovandi, Grace M.

    2013-01-01

    Summary Most infants born to human immunodeficiency virus (HIV)-infected women escape HIV infection. Infants evade infection despite an immature immune system and, in the case of breastfeeding, prolonged repetitive, exposure. If infants become infected, the course of their infection and response to treatment differs dramatically depending upon the timing (in utero, intrapartum, or during breastfeeding) and potentially the route of their infection. Perinatally acquired HIV infection occurs during a critical window of immune development. HIV’s perturbation of this dynamic process may account for the striking age-dependent differences in HIV disease progression. HIV infection also profoundly disrupts the maternal immune system upon which infants rely for protection and immune instruction. Therefore, it is not surprising that infants who escape HIV infection still suffer adverse effects. In this review, we highlight the unique aspects of pediatric HIV transmission and pathogenesis with a focus on mechanisms by which HIV infection during immune ontogeny may allow discovery of key elements for protection and control from HIV. PMID:23772619

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

    SciTech Connect

    Pang, Wei; Wang Ruirui; Yang Liumeng; Liu Changmei; Tien Po Zheng Yongtang

    2008-07-20

    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-1{sub IIIB} entry and replication with EC{sub 50} values of 3.92 {+-} 0.62 and 6.59 {+-} 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1{sub KM018} with EC{sub 50} values of 44.44 {+-} 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC{sub 50} value of 3.04 {+-} 1.20 nM. It also inhibited HIV-2{sub ROD} and HIV-2{sub CBL-20} entry and replication in the {mu}M range. Notably, HR212 was highly effective against T20-resistant strains with EC{sub 50} 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.

  3. Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

    PubMed Central

    Chateau, Morgan L.; Denton, Paul W.; Swanson, Michael D.; McGowan, Ian; Garcia, J. Victor

    2013-01-01

    Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1JRCSF or the MSM-derived transmitted/founder (T/F) virus HIV-1THRO within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1JRCSF and HIV-1THRO, respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1JRCSF and 0% (0/6; log rank p = 0.02) for HIV-1THRO. This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides. PMID:23527295

  4. Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component

    PubMed Central

    O'Keefe, Barry R.; Vojdani, Fakhrieh; Buffa, Viviana; Shattock, Robin J.; Montefiori, David C.; Bakke, James; Mirsalis, Jon; d'Andrea, Anna-Lisa; Hume, Steven D.; Bratcher, Barry; Saucedo, Carrie J.; McMahon, James B.; Pogue, Gregory P.; Palmer, Kenneth E.

    2009-01-01

    To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing GRFT. Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, we also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes. PMID:19332801

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

    PubMed

    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

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

    SciTech Connect

    Boggiano, Cesar; Jiang Shibo; Lu Hong; Zhao Qian; Liu Shuwen; Binley, James; Blondelle, Sylvie E. . E-mail: sylvieb@burnham.org

    2006-09-08

    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-1{alpha} 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.

  7. ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells

    PubMed Central

    van Hamme, John L.; Jansen, Machiel H.; van Dort, Karel A.; Vanderver, Adeline; Rice, Gillian I.; Crow, Yanick J.; Kootstra, Neeltje A.; Kuijpers, Taco W.

    2015-01-01

    Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells. PMID:26629815

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

    PubMed Central

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

    2015-01-01

    Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site of viral production, storage of viral particles in immune complexes, and viral persistence. Whilst 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. A spatial dynamic model of persistent viral replication and spread explains why the development of drug resistance is not a foregone conclusion under conditions where drug concentrations are insufficient to completely block virus replication. These data provide fresh insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and refill the viral reservoir despite potent antiretroviral therapy. PMID:26814962

  9. Inhibiting the HIV Integration Process: Past, Present, and the Future

    PubMed Central

    2013-01-01

    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

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

    PubMed

    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

  11. HIV-1 Fusion Assay

    PubMed Central

    Cavrois, Marielle; Neidleman, Jason; Greene, Warner C.

    2016-01-01

    The HIV-1 fusion assay measures all steps in the HIV-1 life cycle up to and including viral fusion. It relies on the incorporation of a β-lactamase Vpr (BlaM-Vpr) protein chimera into the virion and the subsequent transfer of this chimera into the target cell by fusion (Figure 1). The transfer is monitored by the enzymatic cleavage of CCF2, a fluorescent dye substrate of β-lactamase, loaded into the target cells. Cleavage of the β-lactam ring in CCF2 by β-lactamase changes the fluorescence emission spectrum of the dye from green (520 nm) to blue (447 nm). This change reflects virion fusion and can be detected by flow cytometry (Figure 2).

  12. HIV in military.

    PubMed

    1996-05-31

    The House of Representatives approved a defense authorization bill that requires the Pentagon to discharge service members who test positive for HIV antibodies. This is the second measure of its kind. Last year, Rep. Robert K. Dornan (R-CA) pushed through Congress a similar measure that was repealed after encountering public opposition. President Clinton said he will veto the defense bill in its current form. The bill provides $13 billion in spending beyond the amount the Pentagon requested, resurrects plans for the Star Wars missile defense system, and rescinds Clinton's don't ask, don't tell policy toward gay men and lesbians in the military. Rep. Peter Torkildsen (R-MA) is confident that the HIV provision can be stricken when the bill goes to a House-Senate conference committee in a few weeks. PMID:11363494

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

    PubMed

    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

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

    ERIC Educational Resources Information Center

    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…

  15. HIV-infected mothers' experiences during their infants' HIV testing.

    PubMed

    Shannon, Maureen T

    2015-04-01

    Both survival with HIV and rates of perinatal HIV infection have significantly declined during the past decade, due to antiretroviral therapies that interrupt HIV transmission to the fetus and newborn. Although HIV is no longer routinely fatal to mothers or transmitted to fetuses, and the testing of newborns for HIV has been improved, evidence about HIV-infected mothers' experiences during the months of their infants' HIV testing predates these improvements. This qualitative study on 16 mothers was an analysis of interviews conducted several weeks after testing was completed and all infants had been determined to be uninfected. Mothers reported that their experiences evolved during the months of testing. Initial reactions included maternal trauma and guilt associated with infant testing. They then reported learning to cope with the roller coaster ride of repeated testing with the help of information from clinicians. By the end of the testing period, ambiguity began to resolve as they engaged in tentative maternal-infant attachment and expressed desire for a sense of normalcy. Need for support and fear of stigma persisted throughout. These findings expand current knowledge about this experience and suggest clinical strategies to guide HIV-infected women during this stressful period. PMID:25739368

  16. [Pneumocystosis during HIV infection].

    PubMed

    El Fane, M; Sodqi, M; Oulad Lahsen, A; Chakib, A; Marih, L; Marhoum El Filali, K

    2016-08-01

    Pneumocystosis is an opportunistic disease caused by invasion of unicellular fungus Pneumocystic jirovecii which is responsible for febrile pneumonia among patients with cellular immunodeficiency especially those HIV infected. Despite the decreasing of its incidence due to the introduction of antiretroviral therapy, as well as anti-Pneumocystis prophylaxis among these patients, Pneumocystis pneumonia remains the first AIDS-defining event and a leading cause of mortality among HIV-infected patients. The usual radiological presentation is that of diffuse interstitial pneumonia. The diagnosis is confirmed by the detection of trophozoides and/or cysts P. jirovecii in bronchoalveolar lavage (BAL) samples using several staining techniques. The use of polymerase chain reaction in the BAL samples in conjunction with standard immunofluorescent or colorimetric tests have allowed for more has allowed for more rapid and accurate diagnosis. The standard regimen of treatment is the association of trimethoprim-sulfamethoxazole which has been utilized as an effective treatment with a favourable recovery. Early HIV diagnosis and antiretroviral therapy should reduce the incidence of this dreaded disease. PMID:27349824

  17. HIV-related violence.

    PubMed

    Abdale, F

    1999-10-01

    Statistics are seldom recorded on the incidence of HIV-related verbal or physical abuse. The New York Gay and Lesbian Anti-Violence Project (AVP), and San Francisco's Community United Against Violence are the only known programs to recognize and collect data on HIV-related violence. Psychological abuse, physical battery, harassment, and rape are all signs of domestic violence. Reluctance to report bias crimes is thought to stem from fear of discrimination and further violence. In addition, some community members are concerned that partner notification laws may foster more household violence, or discourage people from being tested. The repercussions of violence against people with HIV is evident, often resulting in depression, lack of sleep, and non-adherence to medication. Those victimized by violent situations can seek assistance in New York from AVP, which provides resources, counseling, legal aid and advocacy for victims. AVP also provides guidance and support through the process of criminal prosecution, and formulating a safety plan. A list of organizations that can assist victims of violence is provided, which includes contact information for each. PMID:11366876

  18. Gauge Blocks - A Zombie Technology.

    PubMed

    Doiron, Ted

    2008-01-01

    Gauge blocks have been the primary method for disseminating length traceability for over 100 years. Their longevity was based on two things: the relatively low cost of delivering very high accuracy to users, and the technical limitation that the range of high precision gauging systems was very small. While the first reason is still true, the second factor is being displaced by changes in measurement technology since the 1980s. New long range sensors do not require master gauges that are nearly the same length as the part being inspected, and thus one of the primary attributes of gauge blocks, wringing stacks to match the part, is no longer needed. Relaxing the requirement that gauges wring presents an opportunity to develop new types of end standards that would increase the accuracy and usefulness of gauging systems. PMID:27096119

  19. Belos Block Linear Solvers Package

    Energy Science and Technology Software Center (ESTSC)

    2004-03-01

    Belos is an extensible and interoperable framework for large-scale, iterative methods for solving systems of linear equations with multiple right-hand sides. The motivation for this framework is to provide a generic interface to a collection of algorithms for solving large-scale linear systems. Belos is interoperable because both the matrix and vectors are considered to be opaque objects--only knowledge of the matrix and vectors via elementary operations is necessary. An implementation of Balos is accomplished viamore » the use of interfaces. One of the goals of Belos is to allow the user flexibility in specifying the data representation for the matrix and vectors and so leverage any existing software investment. The algorithms that will be included in package are Krylov-based linear solvers, like Block GMRES (Generalized Minimal RESidual) and Block CG (Conjugate-Gradient).« less

  20. Dissolution patterns on caramel blocks

    NASA Astrophysics Data System (ADS)

    Cohen, Caroline; Derr, Julien; Berhanu, Michael; Courrech Du Pont, Sylvain

    2015-11-01

    We investigate erosion by dissolution processes. We perform laboratory experiments on hard caramel bodies, which dissolve on a short timescale, compared to geological material such as limestone. We put a block of caramel, tilted from the horizontal, in a water tank without flow. The dissolution syrup, which is denser than pure water, sinks and the flow detaching from the surface creates patterns underneath the caramel block. These patterns result from the coupled dynamics of the flow detaching and the eroding surface and are reminiscent of scallops observed in the walls of phreatic cave passages. We investigate the mechanisms of formation of these structures and their evolution depending on several parameters such as the fluid density or the flow velocity. We finally parallel the formation of patterns on melting iceberg.

  1. Block Copolymers with a Twist

    SciTech Connect

    Ho, R.; Chiang, Y; Chen, C; Wang, H; Hasegawa, H; Akasaka, S; Thomas, E; Burger, C; Hsiao, B

    2009-01-01

    Chiral block copolymers (BCPs*) comprising chiral entities were designed to fabricate helical architectures (i.e., twisted morphologies) from self-assembly. A new helical phase (H*) with P622 symmetry was discovered in the self-assembly of poly(styrene)-b-poly(l-lactide) (PS-PLLA) BCPs*. Hexagonally packed, interdigitated PLLA helical microdomains in a PS matrix were directly visualized by electron tomography. The phase diagram of the PS-PLLA BCPs* was also established. Phase transitions from the H* phase to the stable cylinder and gyroid phases were found after long-time annealing, suggesting that the H* is a long-lived metastable phase. In contrast to racemic poly(styrene)-b-poly(d,l-lactide) BCPs, chiral interaction significantly enhances the incompatibility between achiral PS and chiral PLLA blocks in the PS-PLLA BCPs* and can be estimated through the determination of the interaction parameter.

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

    PubMed Central

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

    2004-01-01

    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. PMID:15485580

  3. Compact planar microwave blocking filters

    NASA Technical Reports Server (NTRS)

    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.

  4. Uav Photogrammetry: Block Triangulation Comparisons

    NASA Astrophysics Data System (ADS)

    Gini, R.; Pagliari, D.; Passoni, D.; Pinto, L.; Sona, G.; Dosso, P.

    2013-08-01

    UAVs systems represent a flexible technology able to collect a big amount of high resolution information, both for metric and interpretation uses. In the frame of experimental tests carried out at Dept. ICA of Politecnico di Milano to validate vector-sensor systems and to assess metric accuracies of images acquired by UAVs, a block of photos taken by a fixed wing system is triangulated with several software. The test field is a rural area included in an Italian Park ("Parco Adda Nord"), useful to study flight and imagery performances on buildings, roads, cultivated and uncultivated vegetation. The UAV SenseFly, equipped with a camera Canon Ixus 220HS, flew autonomously over the area at a height of 130 m yielding a block of 49 images divided in 5 strips. Sixteen pre-signalized Ground Control Points, surveyed in the area through GPS (NRTK survey), allowed the referencing of the block and accuracy analyses. Approximate values for exterior orientation parameters (positions and attitudes) were recorded by the flight control system. The block was processed with several software: Erdas-LPS, EyeDEA (Univ. of Parma), Agisoft Photoscan, Pix4UAV, in assisted or automatic way. Results comparisons are given in terms of differences among digital surface models, differences in orientation parameters and accuracies, when available. Moreover, image and ground point coordinates obtained by the various software were independently used as initial values in a comparative adjustment made by scientific in-house software, which can apply constraints to evaluate the effectiveness of different methods of point extraction and accuracies on ground check points.

  5. Multi-level block permutation

    PubMed Central

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

    2015-01-01

    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

  6. Induction of Potent and Long-Lived Antibody and Cellular Immune Responses in the Genitorectal Mucosa Could be the Critical Determinant of HIV Vaccine Efficacy

    PubMed Central

    Chanzu, Nadia; Ondondo, Beatrice

    2014-01-01

    The field of HIV prevention has indeed progressed in leaps and bounds, but with major limitations of the current prevention and treatment options, the world remains desperate for an HIV vaccine. Sadly, this continues to be elusive, because more than 30 years since its discovery there is no licensed HIV vaccine. Research aiming to define immunological biomarkers to accurately predict vaccine efficacy have focused mainly on systemic immune responses, and as such, studies defining correlates of protection in the genitorectal mucosa, the primary target site for HIV entry and seeding are sparse. Clearly, difficulties in sampling and analysis of mucosal specimens, as well as their limited size have been a major deterrent in characterizing the type (mucosal antibodies, cytokines, chemokines, or CTL), threshold (magnitude, depth, and breadth) and viral inhibitory capacity of HIV-1-specific immune responses in the genitorectal mucosa, where they are needed to immediately block HIV acquisition and arrest subsequent virus dissemination. Nevertheless, a few studies document the existence of HIV-specific immune responses in the genitorectal mucosa of HIV-infected aviremic and viremic controllers, as well as in highly exposed persistently seronegative (HEPS) individuals with natural resistance to HIV-1. Some of these responses strongly correlate with protection from HIV acquisition and/or disease progression, thus providing significant clues of the ideal components of an efficacious HIV vaccine. In this study, we provide an overview of the key features of protective immune responses found in HEPS, elite and viremic controllers, and discuss how these can be achieved through mucosal immunization. Inevitably, HIV vaccine development research will have to consider strategies that elicit potent antibody and cellular immune responses within the genitorectal mucosa or induction of systemic immune cells with an inherent potential to home and persist at mucosal sites of HIV entry. PMID

  7. Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase.

    PubMed

    Cox, Bryan D; Prosser, Anthony R; Sun, Yongnian; Li, Zhufang; Lee, Sangil; Huang, Ming B; Bond, Vincent C; Snyder, James P; Krystal, Mark; Wilson, Lawrence J; Liotta, Dennis C

    2015-07-01

    We report novel anti-HIV-1 agents with combined dual host-pathogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that block HIV-1 entry through dual chemokine receptor ligation. PMID:26191361

  8. Interfaces between Block Copolymer Domains

    NASA Astrophysics Data System (ADS)

    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.

  9. Colostomy with Transversus Abdominis Plane Block.

    PubMed

    Tekelioğlu, Ümit Yaşar; Demirhan, Abdullah; Şit, Mustafa; Kurt, Adem Deniz; Bilgi, Murat; Koçoğlu, Hasan

    2015-12-01

    Transversus abdominis plane (TAP) block is one of the abdominal field block. The TAP block is used for both anaesthetic management and post-operative pain therapy in lower abdominal surgery. TAP block is a procedure in which local anaesthetic agents are applied to the anatomic neurofacial space between the internal oblique and the transversus abdominis muscle. TAP block is a good method for post-operative pain control as well as allows for short operations involving the abdominal area. In this article, a case of colostomy under TAP block is presented. PMID:27366540

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

    PubMed

    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

  11. How you get HIV/AIDS

    MedlinePlus

    How you get HIV/AIDS Which body fluids contain HIV? HIV is a virus that lives in blood and other fluids in ... other fluids) . - an organ transplant . Be sure to get answers to any questions you have about HIV/AIDS. Your public health department and health care provider ...

  12. How you get HIV/AIDS

    MedlinePlus

    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 ...

  13. Trichomoniasis and HIV interactions: a review

    PubMed Central

    Kissinger, Patricia; Adamski, Alys

    2013-01-01

    Objective To discuss the epidemiology of Trichomonas vaginalis (TV) and HIV co-infections, the role of TV in acquisition and transmission of HIV, special treatment considerations for TV among women with HIV and the prevention of TV among HIV-infected persons. Design Systematic review. Data source Review of literature of EMBASE and PubMed databases from January 1990 to February 2013. Search keywords included TV, HIV co-infections, HIV acquisition, HIV transmission, HIV shedding, TV treatment, HIV and couples studies. Review method We included studies of any design that contained the selected search words and were published during the specified time frame. We then searched the reference lists of included papers for additional papers and included these when relevant. Results There is strong evidence that TV increases both transmission and acquisition of HIV among women, and that successful treatment for TV can reduce HIV genital shedding. Single dose metronidazole (MTZ) should no longer be used for HIV+ women with TV given the high rates of asymptomatic bacterial vaginosis co-infections and other factors that may render MTZ less effective in HIV+ women. Prevention of TV among HIV+ persons is similar to among HIV, including promotion of condoms as well as regular screening and prompt treatment. There may be a role for expedited partner treatment for the prevention of repeat infections, but most repeat infections are clinical treatment failures. Diligence in screening and treating TV among both HIV− susceptible and HIV+ persons is an important public health strategy. PMID:23605851

  14. HIV/AIDS and Pregnancy

    MedlinePlus

    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 ...

  15. Hyperthermia Stimulates HIV-1 Replication

    PubMed Central

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

    2012-01-01

    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 investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity. PMID:22807676

  16. HIV, AIDS, and Older People

    MedlinePlus

    ... to lower your risk: If you are having sex, talk with your partner about HIV/AIDS. Know his/her sexual and drug history and make sure your partner has been tested and is free of HIV. Use male or female condoms (latex ...

  17. HIV/AIDS and Pregnancy

    MedlinePlus

    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 ...

  18. Preventing HIV Infection among Youth.

    ERIC Educational Resources Information Center

    Alcohol, Drug Abuse, and Mental Health Administration (DHHS/PHS), Rockville, MD. Office for Substance Abuse Prevention.

    This document notes that a recent threat to American's youth is the risk of infection from the human immunodeficiency virus (HIV). It views youth at high risk for alcohol or other drug use as also being, in all probability, at highest risk for exposure to HIV, and suggests that programs set up to prevent adolescents from becoming involved with…

  19. HIV detection by optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Joshi, Narahari V.; Doria, M.; Medina, Honorio

    2001-10-01

    Reliable and economical Human Immnodeficiency Virus (HIV) testing was achieved by optical absorption spectroscopy of the core of the hair in the range of 400 nm to 800 nm. In HIV+ patients, extra optical active material is deposited in the core and optical absorption spectra, recorded in polarized radiation reveal special features, which can be used for guidance, detection, monitoring and control.

  20. International travel and HIV infection.

    PubMed Central

    von Reyn, C. F.; Mann, J. M.; Chin, J.

    1990-01-01

    Although human immunodeficiency virus (HIV) infection is a worldwide problem, its prevalence and pattern vary from country to country. Accordingly, the risk to international travellers of acquiring HIV infection also varies widely in different parts of the world, and depends principally on their behaviour. The risk of sexual acquisition of HIV infection can be virtually eliminated by avoiding penetrative sexual intercourse with intravenous drug users and persons who have had multiple sexual partners (such as prostitutes) or reduced by the use of condoms. The risk of parenteral exposure to HIV can be reduced by avoiding parenteral drug use and behaviour that is likely to lead to injury (with its attendant risk of requiring blood transfusion) and by seeking medical facilities with adequate capabilities to screen blood donors for HIV and to sterilize instruments. HIV screening of international travellers is an ineffective, costly, and impractical public health strategy for limiting the worldwide spread of HIV infection. Travellers infected with HIV require specialized advice regarding health precautions, prophylactic medications, and immunization. PMID:2194689

  1. HIV Testing among Detained Youth

    ERIC Educational Resources Information Center

    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…

  2. HIV-1 Capsid Stabilization Assay.

    PubMed

    Fricke, Thomas; Diaz-Griffero, Felipe

    2016-01-01

    The stability of the HIV-1 core in the cytoplasm is crucial for productive HIV-1 infection. Mutations that stabilize or destabilize the core showed defects in HIV-1 reverse transcription and infection. We developed a novel and simple assay to measure stability of in vitro-assembled HIV-1 CA-NC complexes. This assay allowed us to demonstrate that cytosolic extracts strongly stabilize the HIV-1 core (Fricke et al., J Virol 87:10587-10597, 2013). By using our novel assay, one can measure the ability of different drugs to modulate the stability of in vitro-assembled HIV-1 CA-NC complexes, such as PF74, CAP-1, IXN-053, cyclosporine A, Bi2, and the peptide CAI. We also found that purified CPSF6 (1-321) protein stabilizes in vitro-assembled HIV-1 CA-NC complexes (Fricke et al., J Virol 87:10587-10597, 2013). Here we describe in detail the use of this capsid stability assay. We believe that our assay can be a powerful tool to assess HIV-1 capsid stability in vitro. PMID:26714703

  3. The future of HIV prevention.

    PubMed

    Padian, Nancy S; Isbell, Michael T; Russell, Elizabeth S; Essex, M

    2012-08-01

    In the decades since the emergence of HIV, numerous approaches to prevent transmission have been tested with varying degrees of success. Because a highly effective vaccine will not be available within the next decade, it is increasingly clear that preventing new HIV infections will require successful implementation of promising behavioral and biomedical interventions in combination. These prevention packages must be sufficiently flexible to include a variety of evidence-based interventions that serve each dynamic population they target, particularly those who are most vulnerable. To optimize the impact of combination intervention packages, well-designed implementation science studies are vital. Efficacy in a clinical trial does not necessarily translate to effectiveness at the population-level, and prioritized research studies should investigate programmatic implementation and operations scale-up and new methods to monitor and evaluate these processes both for organization and cost-effectiveness. With an estimated 2.7 million people becoming newly infected with HIV in 2010, the prevention of HIV remains an urgent global health priority. Since the emergence of HIV/AIDS more than 30 years ago, the evidence base for HIV prevention has expanded and evolved. Here we explore the status of evidence-based HIV prevention, describing both the continuing challenges and the emerging opportunities to reduce HIV incidence. PMID:22772385

  4. MicroRNA-mediated regulation of p21 and TASK1 cellular restriction factors enhances HIV-1 infection

    PubMed Central

    Farberov, Luba; Herzig, Eytan; Modai, Shira; Isakov, Ofer; Hizi, Amnon; Shomron, Noam

    2015-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in the regulation of gene expression by binding to target mRNAs. Several studies have revealed alterations in cellular miRNA profiles following HIV-1 infection, mostly for miRNAs involved in inhibiting viral infection. These miRNA expression modifications might also serve to block the innate HIV-1 inhibition mechanism. As a result, it is expected that during HIV-1 infection miRNAs target genes that hinder or prevent the progression of the HIV-1 replication cycle. One of the major sets of genes known to inhibit the progression of HIV-1 infection are cellular restriction factors. In this study, we identified a direct miRNA target gene that modulates viral spread in T-lymphocytes and HeLa-CCR5 cell lines. Following infection, let-7c, miR-34a or miR-124a were upregulated, and they targeted and downregulated p21 and TASK1 (also known as CDKN1A and KCNK3, respectively) cellular proteins. This eventually led to increased virion release and higher copy number of viral genome transcripts in infected cells. Conversely, by downregulating these miRNAs, we could suppress viral replication and spread. Our data suggest that HIV-1 exploits the host miRNA cellular systems in order to block the innate inhibition mechanism, allowing a more efficient infection process. PMID:25717002

  5. Methamphetamine inhibits Toll-like receptor 9-mediated anti-HIV activity in macrophages.

    PubMed

    Cen, Ping; Ye, Li; Su, Qi-Jian; Wang, Xu; Li, Jie-Liang; Lin, Xin-Qin; Liang, Hao; Ho, Wen-Zhe

    2013-08-01

    Toll-like receptor 9 (TLR9) is one of the key sensors that recognize viral infection/replication in the host cells. Studies have demonstrated that methamphetamine (METH) dysregulated host cell innate immunity and facilitated HIV infection of macrophages. In this study, we present new evidence that METH suppressed TLR9-mediated anti-HIV activity in macrophages. Activation of TLR9 by its agonist CpG-ODN 2216 inhibits HIV replication, which was demonstrated by increased expression of TLR9, interferon (IFN)-α, IFN regulatory factor-7 (IRF-7), myeloid differentiation factor 88 (MyD88), and myxovirus resistance gene A (MxA) in macrophages. However, METH treatment of macrophages greatly compromised the TLR9 signaling-mediated anti-HIV effect and inhibited the expression of TLR9 downstream signaling factors. Dopamine D1 receptor (D1R) antagonists (SCH23390) could block METH-mediated inhibition of anti-HIV activity of TLR9 signaling. Investigation of the underlying mechanisms of the METH action showed that METH treatment selectively down-regulated the expression of TLR9 on macrophages, whereas it had little effect on the expression of other TLRs. Collectively, our results provide further evidence that METH suppresses host cell innate immunity against HIV infection by down-regulating TLR9 expression and its signaling-mediated antiviral effect in macrophages. PMID:23751096

  6. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells

    PubMed Central

    2012-01-01

    Background Quiescent CD4+ T lymphocytes are highly refractory to HIV-1 infection due to a block at reverse transcription. Results Examination of SAMHD1 expression in peripheral blood lymphocytes shows that SAMHD1 is expressed in both CD4+ and CD8+ T cells at levels comparable to those found in myeloid cells. Treatment of CD4+ T cells with Virus-Like Particles (VLP) containing Vpx results in the loss of SAMHD1 expression that correlates with an increased permissiveness to HIV-1 infection and accumulation of reverse transcribed viral DNA without promoting transcription from the viral LTR. Importantly, CD4+ T-cells from patients with Aicardi-Goutières Syndrome harboring mutation in the SAMHD1 gene display an increased susceptibility to HIV-1 infection that is not further enhanced by VLP-Vpx-treatment. Conclusion Here, we identified SAMHD1 as the restriction factor preventing efficient viral DNA synthesis in non-cycling resting CD4+ T-cells. These results highlight the crucial role of SAMHD1 in mediating restriction of HIV-1 infection in quiescent CD4+ T-cells and could impact our understanding of HIV-1 mediated CD4+ T-cell depletion and establishment of the viral reservoir, two of the HIV/AIDS hallmarks. PMID:23092122

  7. Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

    PubMed Central

    Zaidi, Asifa; Meng, Qinglai; Popkin, Daniel

    2016-01-01

    Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4+ T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cell-mediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2hi memory CD4+ T cells are a significant contributor. PMID:27110598

  8. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha

    PubMed Central

    Browne, Edward P.; Letham, Benjamin; Rudin, Cynthia

    2016-01-01

    Type 1 interferons such as interferon-alpha (IFNα) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses. PMID:27010978

  9. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

    PubMed Central

    Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen

    2016-01-01

    Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis. PMID:27257969

  10. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha.

    PubMed

    Browne, Edward P; Letham, Benjamin; Rudin, Cynthia

    2016-01-01

    Type 1 interferons such as interferon-alpha (IFNα) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses. PMID:27010978

  11. Inhibitors of HIV-1 entry and integration: recent developments and impact on treatment.

    PubMed

    Sharma, Anil K; George, Varghese; Valiathan, Ranjini; Pilakka-Kanthikeel, Sudheesh; Pallikkuth, Suresh

    2013-05-01

    Advances in the drug development against HIV-1 have lead to the identification of new compounds which could be used to target cellular entry and nuclear integration of virus in addition to drugs that commonly target reverse transcriptase and protease. These additional targets have added a new dimension to fight against HIV. Cellular entry of HIV is a multistep procedure involving a range of cellular and molecular interactions between virus envelope protein and receptors expressed on the surface of the target cells, thus providing many opportunities to block infection. Some of these entry inhibitors are currently being used in the clinic and more compounds are under various stages of development. Integration of the HIV-1 DNA is required and essential to maintain the viral DNA in the infected cell. The design and discovery of integrase inhibitors were first focused at targeting the catalytic site of integrase that selectively acting on strand transfer and thus inhibits integration of virus DNA with host cell genome. Thus, entry and integrase inhibitors present a real added value in combined treatment against HIV infection. This review discusses the recent development in the discovery of inhibitors of HIV entry and integration along with some of recent patents in the field. PMID:23578097

  12. Control of HIV Latency by Epigenetic and Non-Epigenetic Mechanisms

    PubMed Central

    Mbonye, Uri; Karn, Jonathan

    2011-01-01

    Intensive antiretroviral therapy successfully suppresses viral replication but is unable to eradicate the virus. HIV persists in a small number of resting memory T cells where HIV has been transcriptionally silenced. This review will focus on recent insights into the HIV transcriptional control mechanisms that provide the biochemical basis for understanding latency. There are no specific repressors of HIV transcription encoded by the virus, instead latency arises when the regulatory feedback mechanism driven by HIV Tat expression is disrupted. Small changes in transcriptional initiation, induced by epigenetic silencing, lead to profound restrictions in Tat levels and force the entry of proviruses into latency. In resting memory T cells, which carry the bulk of the latent viral pool, additional restrictions, especially the limiting cellular levels of the essential Tat cofactor P-TEFb and the transcription initiation factors NF-κB and NFAT ensure that the provirus remains silenced unless the host cell is activated. The detailed understanding of HIV transcription is providing a framework for devising new therapeutic strategies designed to purge the latent viral pool. Importantly, the recognition that there are multiple restrictions imposed on latent proviruses suggest that proviral reactivation will not be achieved when only a single reactivation step is targeted and that any optimal activation strategy will require both removal of epigenetic blocks and the activation of P-TEFb. PMID:22211660

  13. HIV surveillance in complex emergencies.

    PubMed

    Salama, P; Dondero, T J

    2001-04-01

    Many studies have shown a positive association between both migration and temporary expatriation and HIV risk. This association is likely to be similar or even more pronounced for forced migrants. In general, HIV transmission in host-migrant or host-forced-migrant interactions depends on the maturity of the HIV epidemic in both the host and the migrant population, the relative seroprevalence of HIV in the host and the migrant population, the prevalence of other sexually transmitted infections (STIs) that may facilitate transmission, and the level of sexual interaction between the two communities. Complex emergencies are the major cause of mass population movement today. In complex emergencies, additional factors such as sexual interaction between forced-migrant populations and the military; sexual violence; increasing commercial sex work; psychological trauma; and disruption of preventive and curative health services may increase the risk for HIV transmission. Despite recent success in preventing HIV infection in stable populations in selected developing countries, internally displaced persons and refugees (or forced migrants) have not been systematically included in HIV surveillance systems, nor consequently in prevention activities. Standard surveillance systems that rely on functioning health services may not provide useful data in many complex emergency settings. Secondary sources can provide some information in these settings. Little attempt has been made, however, to develop innovative HIV surveillance systems in countries affected by complex emergencies. Consequently, data on the HIV epidemic in these countries are scarce and HIV prevention programs are either not implemented or interventions are not effectively targeted. Second generation surveillance methods such as cross-sectional, population-based surveys can provide rapid information on HIV, STIs, and sexual behavior. The risks for stigmatization and breaches of confidentiality must be recognized

  14. Genital HIV-1 RNA Quantity Predicts Risk of Heterosexual HIV-1 Transmission

    PubMed Central

    Baeten, Jared M.; Kahle, Erin; Lingappa, Jairam R.; Coombs, Robert W.; Delany-Moretlwe, Sinead; Nakku-Joloba, Edith; Mugo, Nelly R.; Wald, Anna; Corey, Lawrence; Donnell, Deborah; Campbell, Mary S.; Mullins, James I.; Celum, Connie

    2011-01-01

    High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission. Although plasma and genital HIV-1 RNA concentrations are correlated, no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission. In a prospective study of 2521 African HIV-1 serodiscordant couples, we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk. HIV-1 transmission linkage was established within the partnership by viral sequence analysis. We tested endocervical samples from 1805 women, including 46 who transmitted HIV-1 to their partner, and semen samples from 716 men, including 32 who transmitted HIV-1 to their partner. Genital and plasma HIV-1 concentrations were correlated: For endocervical swabs, Spearman’s rank correlation coefficient rho was 0.56 (p<0.001), and for semen rho was 0.55 (p<0.001). Each 1 log10 increase in genital HIV-1 RNA was associated with a 2.20-fold (for endocervical swabs, 95% confidence interval 1.60–3.04, p<0.001) and a 1.79-fold (for semen, 95% confidence interval 1.30–2.47, p<0.001) increased risk of HIV-1 transmission. Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity (hazard ratio 1.67 for endocervical swabs and 1.68 for semen). Seven female-to-male and four male-to-female HIV-1 transmissions (incidence <1% per year) occurred from persons with undetectable genital HIV-1 RNA, but in all eleven plasma HIV-1 RNA was detected. Thus, higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission, and this effect was independent of plasma HIV-1 concentrations. These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk. PMID:21471433

  15. New Approaches to HIV Vaccine Development

    PubMed Central

    Haynes, Barton F.

    2015-01-01

    Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8 T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design. PMID:26056742

  16. Solid organ transplantation and HIV infection.

    PubMed

    Polak, Wojciech G; Gładysz, Andrzej

    2003-01-01

    HIV infection has been traditionally considered to be an absolute contraindication for solid organ transplantation. Recent advances in HIV treatment, as highly active antiretroviral therapy (HAART), significantly reduced HIV-related mortality and morbidity. At the same time the number of HIV-infected patients with end-stage organ diseases constantly increased. Current data describing solid organ transplantation in HIV-infected patients demonstrated comparable outcome to that in the HIV-negative population. In light of this, solid organ transplantation should be considered as a treatment option for selected HIV-positive patients with end-stage organ disease. PMID:15171000

  17. Designing synthetic vaccines for HIV.

    PubMed

    Fernández-Tejada, Alberto; Haynes, Barton F; Danishefsky, Samuel J

    2015-06-01

    Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines. PMID:25824661

  18. Surrogacy commissioning fathers and HIV.

    PubMed

    Jordaan, Donrich W

    2014-01-01

    Surrogacy is not regulated by a single legal instrument only, nor is confirmation of a surrogacy agreement by the High Court an unqualified green light for the surrogacy process to proceed. In the context of the HIV status of the commissioning father, whose gametes are to be used for the conception of the child in pursuance of a surrogacy agreement, the intended in vitro fertilisation of the surrogate mother may only take place on condition that the commissioning father, and his semen, have been tested for HIV; that he has consented to his HIV status being made available to the surrogate mother, and if he is HIV-positive, that sperm washing will be used to minimise the risk of infection and that the surrogate mother has been informed of his HIV status, and given her informed consent.  PMID:24388075

  19. Cardiovascular Disease, Statins, and HIV.

    PubMed

    Eckard, Allison Ross; Meissner, Eric G; Singh, Inderjit; McComsey, Grace A

    2016-10-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of serious, non-AIDS-defining comorbidities, even in the setting of viral suppression with combination antiretroviral therapy. This increased risk is due in part to immune dysfunction and heightened inflammation and immune activation associated with chronic HIV infection. Statins have wide-reaching immunomodulatory effects, and their use in the HIV-infected population may be of particular benefit. In this article, we review the pathogenesis of increased inflammation during HIV infection and how it contributes to the risk of cardiovascular disease among HIV-infected individuals. We then we review the immunomodulatory effects of statins and how they may attenuate the risk of cardiovascular disease and other comorbidities in this unique patient population. PMID:27625435

  20. HIV treatment in US prisons

    PubMed Central

    Wakeman, Sarah E; Rich, Josiah D

    2010-01-01

    Arguably one of the most marginalized populations in our society, prisoners bear a disproportionate burden of infectious diseases, particularly HIV. In addition, groups known to be at an inordinately higher risk of HIV, including minorities, the addicted, the mentally ill and the impoverished are overrepresented among incarcerated populations. This concentration of HIV among groups that have been historically difficult to reach, with limited intersections with healthcare, provides an opportunity for testing, diagnosis, treatment, linkage to care and prevention. Providing HIV care within correctional facilities poses unique challenges. Barriers to confidentiality, access to medication and prior records, and lack of comprehensive discharge planning can serve as obstacles to providing optimal care. This article discusses the public health implications and importance of providing HIV care to prisoners, and also discusses the practicalities of working within an environment that poses particular barriers to care. PMID:20953349

  1. Internal-image anti-idiotype HIV-1gp120 antibody in human immunodeficiency virus 1 (HIV-1)-seropositive individuals with thrombocytopenia.

    PubMed Central

    Karpatkin, S; Nardi, M A; Kouri, Y H

    1992-01-01

    Anti-CD4 antibody was found in 30% of human immunodeficiency virus (HIV-1)-seropositive thrombocytopenic patients compared with 5% of nonthrombocytopenic seropositive patients (chi 2 = 21.7, P less than 0.001) and was shown by the following observations to contain internal-image anti-idiotype antibody (Ab2) directed against the antibody (Ab1) to gp120, the HIV-1 envelope glycoprotein that binds to CD4: (i) affinity-purified anti-CD4 (Ab2) bound to affinity-purified anti-HIV-1gp120 (Ab1) on solid-phase radioimmunoassay, and binding could be blocked by recombinant CD4 (rCD4) as well as recombinant gp120 (rgp120); (ii) F(ab')2 fragments of Ab1 inhibited the binding of Ab2 to rCD4; (iii) Ab2 inhibited the binding of Ab1 to HIV-1 beads; (iv) Ab2 inhibited the binding of Ab1 to gp120 on immunoblot; (v) Ab2 bound to the CD4 receptor on a CD4-bearing T-cell line, H9; (vi) Ab3 (anti-rgp120) could be produced in vivo by immunizing mice with Ab2, and binding of Ab3 to rgp120 could be blocked with rCD4; and (vii) three different Ab2 preparations bound to two different homologous Ab1 preparations. Ab1 or Ab2 alone did not bind to platelets, whereas the idiotype-anti-idiotype complex did bind to platelets in a concentration-dependent manner. Binding of the internal-image complex was 10-fold greater than that of a non-internal-image Ab1-Ab2 complex composed of anti-HIV-1gp120 and anti-anti-HIV-1gp120. Thus, patients with HIV-1 thrombocytopenia contain internal-image idiotype-anti-idiotype complexes that could be affecting CD4 cell number or function, inhibiting HIV-1 binding to CD4 cells or contributing to HIV-1 thrombocytopenia. Images PMID:1741404

  2. The effect of the amount of blocking cue training on blocking of appetitive conditioning in mice

    PubMed Central

    Sanderson, David J.; Jones, William S.; Austen, Joseph M.

    2016-01-01

    Conditioning of a target cue is blocked when it occurs in compound with another cue (blocking cue) that has already received conditioning. Although blocking of appetitive conditioning is commonly used in rodents as a test of selective learning, it has been demonstrated rarely in mice. In order to investigate the conditions that result in blocking in mice two studies tested the effect of the extent of prior blocking cue training on blocking of appetitive conditioning. Mice received either 80 or 200 trials of blocking cue training prior to compound conditioning. A control group received only compound training. Experiment 1 assessed the ability of a visual cue to block conditioning to an auditory target cue. Exposure to the context and the unconditioned stimulus, sucrose pellets, was equated across groups. Blocking was evident in mice that received 200, but not 80 training trials with the visual blocking cue. Responding to the blocking cue was similar across groups. Experiment 2 assessed the ability of an auditory cue to block conditioning to a visual target cue. Blocking was evident in mice trained with 80 and 200 auditory blocking cue trials. The results demonstrate that the strength of blocking in mice is dependent on the modality and experience of the blocking cue. Furthermore, prolonged training of the blocking cue after asymptotic levels of conditioned responding have been reached is necessary for blocking to occur under certain conditions suggesting that the strength of conditioned responding is a limited measure of learning. PMID:26562656

  3. Using Quilt Blocks to Construct Understanding

    ERIC Educational Resources Information Center

    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.)

  4. Hillslope-derived blocks retard river incision

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed

    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. HIV Interaction With Human Host: HIV-2 As a Model of a Less Virulent Infection.

    PubMed

    Azevedo-Pereira, José Miguel; Santos-Costa, Quirina

    2016-01-01

    HIV-1 and HIV-2 are the causal agents of AIDS. While similar in many ways, a significant amount of data suggests that HIV-2 is less virulent than HIV-1. In fact, HIV-2 infection is characterized by a longer asymptomatic stage and lower transmission rate, and the majority of HIV-2-infected patients can be classified as long-term non-progressors or elite controllers. The mechanisms underlying the ability of human host to naturally control HIV-2 infection are far from being completely understood. The identification of the differences between HIV-1 and HIV-2 interactions with human host cells could provide important insights into several aspects of retroviral pathogenesis that remain elusive, with significant implications for HIV vaccine development and therapy. In this review, we delve into some of the differences that notably distinguish HIV-2 from HIV-1, highlighting possible consequences in the pathogenesis and natural history of both infections. PMID:26936760

  7. Adapting the minority stress model: associations between gender non-conformity stigma, HIV-related stigma and depression among men who have sex with men in South India.

    PubMed

    Logie, Carmen H; Newman, Peter A; Chakrapani, Venkatesan; Shunmugam, Murali

    2012-04-01

    Marginalization and stigmatization heighten the vulnerability of sexual minorities to inequitable mental health outcomes. There is a dearth of information regarding stigma and mental health among men who have sex with men (MSM) in India. We adapted Meyer's minority stress model to explore associations between stigma and depression among MSM in South India. The study objective was to examine the influence of sexual stigma, gender non-conformity stigma (GNS) and HIV-related stigma (HIV-S) on depression among MSM in South India. A cross-sectional survey was administered to MSM in urban (Chennai) (n=100) and semi-urban (Kumbakonam) (n=100) locations in Tamil Nadu. The majority of participants reported moderate/severe depression scores. Participants in Chennai reported significantly higher levels of GNS, social support and resilient coping, and lower levels of HIV-S and depression, than participants in Kumbakonam. Hierarchical block regression analyses were conducted to measure associations between independent (GNS, HIV-S), moderator (social support, resilient coping) and dependent (depression) variables. Sexual stigma was not included in regression analyses due to multicollinearity with GNS. The first regression analyses assessed associations between depression and stigma subtypes. In Chennai, perceived GNS was associated with depression; in Kumbakonam enacted/perceived GNS and vicarious HIV-S were associated with depression. In the moderation analyses, overall GNS and HIV-S scores (subtypes combined) accounted for a significant amount of variability in depression in both locations, although HIV-S was only a significant predictor in Kumbakonam. Social support and resilient coping were associated with lower depression but did not moderate the influence of HIV-S or GNS on depression. Differences in stigma, coping, social support and depression between locations highlight the salience of considering geographical context in stigma analyses. Associations between HIV-S and

  8. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models

    PubMed Central

    Raulji, Payal; Mohapatra, Subhra; Mohapatra, Shyam S

    2015-01-01

    Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections. PMID:26407080

  9. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    PubMed

    Boyapalle, Sandhya; Xu, Weidong; Raulji, Payal; Mohapatra, Subhra; Mohapatra, Shyam S

    2015-01-01

    Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections. PMID:26407080

  10. Workflow in interventional radiology: nerve blocks and facet blocks

    NASA Astrophysics Data System (ADS)

    Siddoway, Donald; Ingeholm, Mary Lou; Burgert, Oliver; Neumuth, Thomas; Watson, Vance; Cleary, Kevin

    2006-03-01

    Workflow analysis has the potential to dramatically improve the efficiency and clinical outcomes of medical procedures. In this study, we recorded the workflow for nerve block and facet block procedures in the interventional radiology suite at Georgetown University Hospital in Washington, DC, USA. We employed a custom client/server software architecture developed by the Innovation Center for Computer Assisted Surgery (ICCAS) at the University of Leipzig, Germany. This software runs in an internet browser, and allows the user to record the actions taken by the physician during a procedure. The data recorded during the procedure is stored as an XML document, which can then be further processed. We have successfully gathered data on a number if cases using a tablet PC, and these preliminary results show the feasibility of using this software in an interventional radiology setting. We are currently accruing additional cases and when more data has been collected we will analyze the workflow of these procedures to look for inefficiencies and potential improvements.

  11. Method for making block siloxane copolymers

    DOEpatents

    Butler, Nora; Jessop, Edward S.; Kolb, John R.

    1982-01-01

    A method for synthesizing block polysiloxane copolymers. Diorganoscyclosiloxanes and an end-blocking compound are interacted in the presence of a ring opening polymerization catalyst, producing a blocked prepolymer. The prepolymer is then interacted with a silanediol, resulting in condensation polymerization of the prepolymers. A second end-blocking compound is subsequently introduced to end-cap the polymers and copolymers formed from the condensation polymerization.

  12. Method for making block siloxane copolymers

    DOEpatents

    Butler, N.L.; Jessop, E.S.; Kolb, J.R.

    1981-02-25

    A method for synthesizing block polysiloxane copolymers is disclosed. Diorganoscyclosiloxanes and an end-blocking compound are interacted in the presence of a ring opening polymerization catalyst, producing a blocked prepolymer. The prepolymer is then interacted with a silanediol, resulting in condensation polymerization of the prepolymers. A second end-blocking compound is subsequently introduced to end-cap the polymers and copolymers formed from the condensation polymerization.

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

    PubMed

    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. Standardized Curriculum for Brick, Block, and Stonemasonry.

    ERIC Educational Resources Information Center

    Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

    Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: brick, block, and stonemasonry I and II. The six units in brick, block, and stonemasonry I are as follows: orientation and leadership activities; safety; basic tools and equipment; masonry units; mortar; and wall layout. Brick, block,…

  15. Bullet-Block Science Video Puzzle

    ERIC Educational Resources Information Center

    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…

  16. Encoders for block-circulant LDPC codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  17. 31 CFR 515.319 - Blocked account.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 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...

  18. 31 CFR 515.319 - Blocked account.

    Code of Federal Regulations, 2010 CFR

    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...

  19. 31 CFR 500.319 - Blocked account.

    Code of Federal Regulations, 2010 CFR

    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. 43 CFR 8.4 - Blocking out.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Blocking out. 8.4 Section 8.4 Public Lands: Interior Office of the Secretary of the Interior JOINT POLICIES OF THE DEPARTMENTS OF THE INTERIOR AND OF THE ARMY RELATIVE TO RESERVOIR PROJECT LANDS § 8.4 Blocking out. Blocking out will be accomplished...