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Sample records for vivo hiv fitness

  1. vFitness: a web-based computing tool for improving estimation of in vitro HIV-1 fitness experiments

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    Demeter Lisa

    2010-05-01

    Full Text Available Abstract Background The replication rate (or fitness between viral variants has been investigated in vivo and in vitro for human immunodeficiency virus (HIV. HIV fitness plays an important role in the development and persistence of drug resistance. The accurate estimation of viral fitness relies on complicated computations based on statistical methods. This calls for tools that are easy to access and intuitive to use for various experiments of viral fitness. Results Based on a mathematical model and several statistical methods (least-squares approach and measurement error models, a Web-based computing tool has been developed for improving estimation of virus fitness in growth competition assays of human immunodeficiency virus type 1 (HIV-1. Conclusions Unlike the two-point calculation used in previous studies, the estimation here uses linear regression methods with all observed data in the competition experiment to more accurately estimate relative viral fitness parameters. The dilution factor is introduced for making the computational tool more flexible to accommodate various experimental conditions. This Web-based tool is implemented in C# language with Microsoft ASP.NET, and is publicly available on the Web at http://bis.urmc.rochester.edu/vFitness/.

  2. Fitness ranking of individual mutants drives patterns of epistatic interactions in HIV-1.

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    Javier P Martínez

    Full Text Available Fitness interactions between mutations, referred to as epistasis, can strongly impact evolution. For RNA viruses and retroviruses with their high mutation rates, epistasis may be particularly important to overcome fitness losses due to the accumulation of deleterious mutations and thus could influence the frequency of mutants in a viral population. As human immunodeficiency virus type 1 (HIV-1 resistance to azidothymidine (AZT requires selection of sequential mutations, it is a good system to study the impact of epistasis. Here we present a thorough analysis of a classical AZT-resistance pathway (the 41-215 cluster of HIV-1 variants by fitness measurements in single round infection assays covering physiological drug concentrations ex vivo. The sign and value of epistasis varied and did not predict the epistatic effect on the mutant frequency. This complex behavior is explained by the fitness ranking of the variants that strongly depends on environmental factors, i.e., the presence and absence of drugs and the host cells used. Although some interactions compensate fitness losses, the observed small effect on the relative mutant frequencies suggests that epistasis might be inefficient as a buffering mechanism for fitness losses in vivo. While the use of epistasis-based hypotheses to make general assumptions on the evolutionary dynamics of viral populations is appealing, our data caution their interpretation without further knowledge on the characteristics of the viral mutant spectrum under different environmental conditions.

  3. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

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    Goudsmit, J.; Lange, J. M.; Smit, L.; Bakker, M.; Klaver, B.; Danner, S. A.; Coutinho, R. A.

    1988-01-01

    Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months

  4. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

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    Wan-Lin Yang

    2015-03-01

    Full Text Available Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS. All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V to 2.7/100-person-years;[0.7, 10.9] (for 215D. RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs. When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

  5. Biology of HIV-Nef in vivo

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    Koenen, P.G.F.

    2007-01-01

    HIV-Nef is established as an important factor for pathogenicity during HIV infection. The exact role and underlying mechanisms however are still unclear. Several studies have shown that Nef expression in T cells results in increased T cell activation. This Nef-mediated T cell activation has been

  6. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

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    Ole S Søgaard

    2015-09-01

    Full Text Available Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03. Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04. Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2 were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.clinicaltrials.gov NTC02092116.

  7. Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam Cohort

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    Gali, Youssef; Berkhout, Ben; Vanham, Guido; Bakker, Margreet; Back, Nicole K. T.; Arien, Kevin K.

    2007-01-01

    Changes in virulence and fitness during an epidemic are common among pathogens. Several studies have shown that HIV fitness increases within a patient during disease progression, while bottlenecks, such as sexual transmission, immune pressure and drug treatment can reduce fitness. In this study, we

  8. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL response.

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    Ryan M Troyer

    2009-04-01

    Full Text Available Human lymphocyte antigen (HLA-restricted CD8(+ cytotoxic T lymphocytes (CTL target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.

  9. Fitness

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    ... gov home http://www.girlshealth.gov/ Home Fitness Fitness Want to look and feel your best? Physical ... are? Check out this info: What is physical fitness? top Physical fitness means you can do everyday ...

  10. Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations

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    Kunz, Anjali N.; Begum, Afrin A.; Wu, Hong; D'Ambrozio, Jonathan A.; Robinson, James M.; Shafer, William M.; Bash, Margaret C.; Jerse, Ann E.

    2012-01-01

    Background. Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA91/95 and parC86 mutations on gonococcal fitness. Methods. Mutant gyrA91/95 and parC86 alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR−79 mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results. In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA91/95 mutation conferred an in vivo fitness benefit to wild-type and mtrR−79 mutant gonococci. The gyrA91/95, parC86 mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA91/95, parC86, mtrR−79 mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (CipR) mutant was selected during infection with the gyrA91/95, parC86, mtrR−79 mutant in which the mtrR−79 mutation was repaired and the gyrA91 mutation was altered. This in vivo–selected mutant grew as well as the wild-type strain in vitro. Conclusions. gyrA91/95 mutations may contribute to the spread of QRNG. Further acquisition of a parC86 mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain CipR. PMID:22492860

  11. Perceptions of condom fit and feel among men living with HIV.

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    Reece, Michael; Briggs, Lindsay; Dodge, Brian; Herbenick, Debby; Glover, Richard

    2010-07-01

    Promoting consistent and correct condom use remains a priority public health activity, although some HIV- and STI-related providers remain challenged by some men's resistance to condoms, which some claim do not fit properly or do not feel comfortable. Although these perceptions have been examined across multiple populations, they have not been documented among men living with HIV. During spring 2008, data were collected from 215 men living with HIV at HIV service organizations in the Midwestern and Southeastern United States. Participants completed the Condom Fit and Feel Scale and measures related to demographics and condom use during sexual interactions within the past 90 days. Men were primarily homosexual, African American, with a high school degree or higher, and unemployed. More than half of participants had used condoms for sexual intercourse within the previous 90 days. The majority of the men reported few problems with the fit and feel of condoms, with 63.1% reporting that condoms "fit my penis just fine," and 80.9% reported being able consistently to find condoms that they perceived to be "sized appropriately for my penis." Some men did report specific characteristics of condoms that challenged fit and feel, including 20.6% endorsing (always or often) that condoms feel too tight, 15.9% that condoms are too short, 17.8% or that condoms would not roll down far enough to cover their penis completely (15.6%). These data provide insights into mechanisms through which providers can help to increase men's access to the diverse range of condoms in the marketplace.

  12. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

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    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  13. Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo.

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    Andrea Introini

    2013-02-01

    Full Text Available The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl-2. Also, IL-7 increased the fraction of cycling CD4⁺ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection.

  14. Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo

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    Rogers A. Ñahui Palomino

    2017-05-01

    Full Text Available Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1 infection. We identified at least three factors that mediated this suppression: (i Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink

  15. Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector

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    Bryan P Burke

    2015-01-01

    Full Text Available We described earlier a dual-combination anti-HIV type 1 (HIV-1 lentiviral vector (LVsh5/C46 that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1 vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.

  16. Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.

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    Oliver F Brandenberg

    2017-05-01

    Full Text Available The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials.

  17. Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations

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    Laird, Gregory M.; Bullen, C. Korin; Rosenbloom, Daniel I.S.; Martin, Alyssa R.; Hill, Alison L.; Durand, Christine M.; Siliciano, Janet D.; Siliciano, Robert F.

    2015-01-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

  18. The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.

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    Crépin, Sébastien; Ottosen, Elizabeth N; Peters, Katharina; Smith, Sara N; Himpsl, Stephanie D; Vollmer, Waldemar; Mobley, Harry L T

    2018-06-08

    Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  19. Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

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    Maja Kiselinova

    2016-03-01

    Full Text Available The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6 between time point 1 and 2; and median of 31 days (IQR: 28-36 between time point 2 and 3. Patients were median of 6 years (IQR: 3-12 on ART, and plasma viral load (<50 copies/ml was suppressed for median of 4 years (IQR: 2-8. Total HIV-1 DNA, unspliced (us and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85, us HIV-1 RNA (p = 0.029, R² = 0.40, and VOA (p = 0.041, R2 = 0.44. Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54. The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1. Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the

  20. Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease

    Czech Academy of Sciences Publication Activity Database

    Kožíšek, Milan; Henke, S.; Grantz Šašková, Klára; Jacobs, G. B.; Schuch, A.; Buchholz, B.; Müller, V.; Kräusslich, H. G.; Řezáčová, Pavlína; Konvalinka, Jan; Bodem, J.

    2012-01-01

    Roč. 56, č. 8 (2012), s. 4320-4330 ISSN 0066-4804 R&D Projects: GA ČR GAP207/11/1798 Institutional research plan: CEZ:AV0Z40550506 Keywords : HIV protease * resistance * inhibitor * viral fitness * AG subtype Subject RIV: EE - Microbiology, Virology Impact factor: 4.565, year: 2012

  1. The fitness landscape of HIV-1 gag: advanced modeling approaches and validation of model predictions by in vitro testing.

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    Jaclyn K Mann

    2014-08-01

    Full Text Available Viral immune evasion by sequence variation is a major hindrance to HIV-1 vaccine design. To address this challenge, our group has developed a computational model, rooted in physics, that aims to predict the fitness landscape of HIV-1 proteins in order to design vaccine immunogens that lead to impaired viral fitness, thus blocking viable escape routes. Here, we advance the computational models to address previous limitations, and directly test model predictions against in vitro fitness measurements of HIV-1 strains containing multiple Gag mutations. We incorporated regularization into the model fitting procedure to address finite sampling. Further, we developed a model that accounts for the specific identity of mutant amino acids (Potts model, generalizing our previous approach (Ising model that is unable to distinguish between different mutant amino acids. Gag mutation combinations (17 pairs, 1 triple and 25 single mutations within these predicted to be either harmful to HIV-1 viability or fitness-neutral were introduced into HIV-1 NL4-3 by site-directed mutagenesis and replication capacities of these mutants were assayed in vitro. The predicted and measured fitness of the corresponding mutants for the original Ising model (r = -0.74, p = 3.6×10-6 are strongly correlated, and this was further strengthened in the regularized Ising model (r = -0.83, p = 3.7×10-12. Performance of the Potts model (r = -0.73, p = 9.7×10-9 was similar to that of the Ising model, indicating that the binary approximation is sufficient for capturing fitness effects of common mutants at sites of low amino acid diversity. However, we show that the Potts model is expected to improve predictive power for more variable proteins. Overall, our results support the ability of the computational models to robustly predict the relative fitness of mutant viral strains, and indicate the potential value of this approach for understanding viral immune evasion

  2. Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells.

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    Rahul Sampath

    Full Text Available HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018 without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches.

  3. Where and how does physical therapy fit? Integrating physical therapy into interprofessional HIV care.

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    deBoer, Heather; Andrews, Matthew; Cudd, Stephanie; Leung, Ellie; Petrie, Alana; Chan Carusone, Soo; O'Brien, Kelly K

    2018-03-13

    To investigate the role of physical therapy in HIV care from the perspective of people living with HIV and health care professionals with expertise in HIV care. We conducted a qualitative descriptive study using semistructured interviews (with health care professionals) and focus groups (with people living with HIV). We purposively sampled health care professionals and recruited people living with HIV in collaboration with an HIV-specialty hospital. We asked participants about their knowledge of and experiences with physical therapy, and perceptions of the physical therapy role in interprofessional HIV care. We analyzed data using content analytical techniques. Thirteen people living with HIV and 12 health care professionals conceptualized physical therapy as positively influencing independence and social participation, and as a valuable ally in interprofessional collaboration. The Framework of Physical Therapy Role in HIV Care consists of two components: (1) multidimensional and client-centered roles of physical therapy addressing physical, psychological and social health domains; and (2) contextual factors important to consider for the role of physical therapy: aging, episodic nature of HIV, multimorbidity, competing priorities, continuity of care, stigma, resource security and social isolation. The interaction between contextual factors and health domains can influence the role of physical therapy. The role of physical therapy in HIV is multidimensional and client-centered. This Framework can be used by rehabilitation professionals working with people living with HIV. Implications for Rehabilitation Participants living with HIV in this study experienced physical therapy as a means of addressing rehabilitation goals that positively influenced physical health and social participation. The role of physical therapy in HIV care is multidimensional and client-centered and can address health challenges in physical, social and psychological health domains. The presence

  4. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment

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    Monajemi Mahdis

    2012-04-01

    Full Text Available Abstract The enzyme APOBEC3G (A3G mutates the human immunodeficiency virus (HIV genome by converting deoxycytidine (dC to deoxyuridine (dU on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.

  5. A Mos1 transposase in vivo assay to screen new HIV-1 integrase inhibitors.

    Science.gov (United States)

    Cancian, Mariana; Loreto, Elgion L S

    2018-04-01

    The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir. The gene expression of the mariner transposase gene, estimated by qPCR, is similar among treated and control flies. The results suggest that in vivo assays using Drosophila can be used as a primary screening of inhibitory drugs for transposase and retroviral integrase. The advantages of this assay are that it is easy, quick, cheap and is an in vivo test, meaning that the tested substance has to have been taken in by cells and has arrived at the target site, which is not the case when in vitro assays are applied.

  6. In vitro and ex vivo evaluations on transdermal delivery of the HIV inhibitor IQP-0410.

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    Anthony S Ham

    Full Text Available The aim of this study was to investigate the physicochemical and in vitro/ex vivo characteristics of the pyrmidinedione IQP-0410 formulated into transdermal films. IQP-0410 is a potent therapeutic anti-HIV nonnucleoside reverse transcriptase inhibitor that would be subjected to extensive first pass metabolism, through conventional oral administration. Therefore, IQP-0410 was formulated into ethyl cellulose/HPMC-based transdermal films via solvent casting. In mano evaluations were performed to evaluate gross physical characteristics. In vitro release studies were performed in both Franz cells and USP-4 dissolution vessels. Ex vivo release and permeability assays were performed on human epidermal tissue models, and the permeated IQP-0410 was collected for in vitro HIV-1 efficacy assays in CEM-SS cells and PBMCs. Film formulation D3 resulted in pliable, strong transdermal films that were loaded with 2% (w/w IQP-0410. Composed of 60% (w/w ethyl cellulose and 20% (w/w HPMC, the films contained < 1.2% (w/w of water and were hygroscopic resulting in significant swelling under humid conditions. The water permeable nature of the film resulted in complete in vitro dissolution and drug release in 26 hours. When applied to ex vivo epidermal tissues, the films were non-toxic to the tissue and also were non-toxic to HIV target cells used in the in vitro efficacy assays. Over a 3 day application, the films delivered IQP-0410 through the skin tissue at a zero-order rate of 0.94 ± 0.06 µg/cm(2/hr with 134 ± 14.7 µM collected in the basal media. The delivered IQP-0410 resulted in in vitro EC50 values against HIV-1 of 2.56 ± 0.40 nM (CEM-SS and 0.58 ± 0.03 nM (PBMC. The film formulation demonstrated no significant deviation from target values when packaged in foil pouches under standard and accelerated environmental conditions. It was concluded that the transdermal film formulation was a potentially viable method of administering IQP-0410 that warrants

  7. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control.

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    Adam R Hersperger

    2010-05-01

    Full Text Available Many immune correlates of CD8(+ T-cell-mediated control of HIV replication, including polyfunctionality, proliferative ability, and inhibitory receptor expression, have been discovered. However, no functional correlates using ex vivo cells have been identified with the known ability to cause the direct elimination of HIV-infected cells. We have recently discovered the ability of human CD8(+ T-cells to rapidly upregulate perforin--an essential molecule for cell-mediated cytotoxicity--following antigen-specific stimulation. Here, we examined perforin expression capability in a large cross-sectional cohort of chronically HIV-infected individuals with varying levels of viral load: elite controllers (n = 35, viremic controllers (n = 29, chronic progressors (n = 27, and viremic nonprogressors (n = 6. Using polychromatic flow cytometry and standard intracellular cytokine staining assays, we measured perforin upregulation, cytokine production, and degranulation following stimulation with overlapping peptide pools encompassing all proteins of HIV. We observed that HIV-specific CD8(+ T-cells from elite controllers consistently display an enhanced ability to express perforin directly ex vivo compared to all other groups. This ability is not restricted to protective HLA-B haplotypes, does not require proliferation or the addition of exogenous factors, is not restored by HAART, and primarily originates from effector CD8(+ T-cells with otherwise limited functional capability. Notably, we found an inverse relationship between HIV-specific perforin expression and viral load. Thus, the capability of HIV-specific CD8(+ T-cells to rapidly express perforin defines a novel correlate of control in HIV infection.

  8. Ex vivo response to histone deacetylase (HDAC inhibitors of the HIV long terminal repeat (LTR derived from HIV-infected patients on antiretroviral therapy.

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    Hao K Lu

    Full Text Available Histone deacetylase inhibitors (HDACi can induce human immunodeficiency virus (HIV transcription from the HIV long terminal repeat (LTR. However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+ isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART. We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

  9. Identification of metabolic pathways essential for fitness of Salmonella Typhimurium in vivo.

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    Lotte Jelsbak

    Full Text Available Bacterial infections remain a threat to human and animal health worldwide, and there is an urgent need to find novel targets for intervention. In the current study we used a computer model of the metabolic network of Salmonella enterica serovar Typhimurium and identified pairs of reactions (cut sets predicted to be required for growth in vivo. We termed such cut sets synthetic auxotrophic pairs. We tested whether these would reveal possible combined targets for new antibiotics by analyzing the performance of selected single and double mutants in systemic mouse infections. One hundred and two cut sets were identified. Sixty-three of these included only pathways encoded by fully annotated genes, and from this sub-set we selected five cut sets involved in amino acid or polyamine biosynthesis. One cut set (asnA/asnB demonstrated redundancy in vitro and in vivo and showed that asparagine is essential for S. Typhimurium during infection. trpB/trpA as well as single mutants were attenuated for growth in vitro, while only the double mutant was a cut set in vivo, underlining previous observations that tryptophan is essential for successful outcome of infection. speB/speF,speC was not affected in vitro but was attenuated during infection showing that polyamines are essential for virulence apparently in a growth independent manner. The serA/glyA cut-set was found to be growth attenuated as predicted by the model. However, not only the double mutant, but also the glyA mutant, were found to be attenuated for virulence. This adds glycine production or conversion of glycine to THF to the list of essential reactions during infection. One pair (thrC/kbl showed true redundancy in vitro but not in vivo demonstrating that threonine is available to the bacterium during infection. These data add to the existing knowledge of available nutrients in the intra-host environment, and have identified possible new targets for antibiotics.

  10. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

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    Sandhya Vasan

    Full Text Available DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.

  11. Anatomic humeral head replacement with a press-fit prosthesis: An in vivo radiographic study

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    Bryan Vopat

    2017-10-01

    Full Text Available Successful total shoulder arthroplasty is, in part, dependent on anatomic reconstruction of the glenohumeral joint. The purpose of this study was to evaluate the post-operative anatomy of total shoulder arthroplasty with an anatomic implant design in patients with primary glenohumeral osteoarthritis and compare it to published normative anatomic measurements. Fifty-one patients (56 shoulders with primary glenohumeral osteoarthritis were treated with a press-fit humeral component as part of a total shoulder arthroplasty (Aequalis, Tornier, Edina, Minnesota. Analysis of postoperative true anterior posterior radiographs was performed with use of a custom software algorithm. The mean humeral inclination (head-shaft angle, mean humeral implant anatomical humeral axis, mean greater tuberosity height, and mean humeral head center offset (medial offset were 135.4±5.1°, 1.73±1.7°, 6.9±2.4 mm, and 3.8±1.8 mm, respectively. All parameters were within the ranges reported in the literature for normal shoulders except the mean humeral head center offset, which was less than reported in the literature. Anatomic parameters of a total shoulder arthroplasty can be achieved with an anatomically designed, modular adaptable press-fit design. Reduced medial humeral head center offset was likely dependent upon implant specific design parameters.

  12. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

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    Michael S Harper

    Full Text Available HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8 and weak (IFNα1 subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

  13. HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

    Science.gov (United States)

    Agarwal, Neeti; Iyer, Dinakar; Patel, Sanjeet G.; Sekhar, Rajagopal V.; Phillips, Terry M.; Schubert, Ulrich; Oplt, Toni; Buras, Eric D.; Samson, Susan L.; Couturier, Jacob; Lewis, Dorothy E.; Rodriguez-Barradas, Maria C.; Jahoor, Farook; Kino, Tomoshige; Kopp, Jeffrey B.; Balasubramanyam, Ashok

    2014-01-01

    Viral infections, such as HIV, have been linked to obesity, but mechanistic evidence that they cause adipose dysfunction in vivo is lacking. We investigated a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients tested, including those on antiretroviral therapy (ART) with undetectable viral load. Vpr-mediated mechanisms were dissected in vivo using mouse models expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis, hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots in these mice had diminished mass, macrophage infiltration, and blunted PPARγ target gene expression but increased GR target gene expression. In liver, we observed blunted PPARα target gene expression, steatosis with decreased adenosine monophosphate– activated protein kinase activity, and insulin resistance. Similar to human HIV-infected patients, Vpr circulated in the serum of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally altered association of PPARγ and GR with their target promoters. These results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle control to produce adipose dysfunction and hepatosteatosis. Confirmation of these mechanisms in HIV patients could lead to targeted treatment of the metabolic complications with Vpr inhibitors, GR antagonists, or PPARγ/PPARα agonists. PMID:24285483

  14. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide.

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    Lisa C Rohan

    2010-02-01

    Full Text Available Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy.Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohistochemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures.These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective

  15. New Approaches for Quantitating the Inhibition of HIV-1 Replication by Antiviral Drugs in vitro and in vivo

    Science.gov (United States)

    McMahon, Moira A.; Shen, Lin; Siliciano, Robert F.

    2014-01-01

    Purpose of review With highly active anti-retroviral therapy (HAART), HIV-1 infection has become a manageable lifelong disease. Developing optimal treatment regimens requires understanding how to best measure anti-HIV activity in vitro and how drug dose response curves generated in vitro correlate with in vivo efficacy. Recent findings Several recent studies have indicated that conventional multi-round infectivity assays are inferior to single cycle assays at both low and high levels of inhibition. Multi-round infectivity assays can fail to detect subtle but clinically significant anti-HIV activity. The discoveries of the anti-HIV activity of the hepatitis B drug entecavir and the herpes simplex drug acyclovir were facilitated by single round infectivity assays. Recent studies using a single round infectivity assay have shown that a previously neglected parameter, the dose response curve slope, is an extremely important determinant of antiviral activity. Some antiretroviral drugs have steep slopes that result in extraordinary levels of antiviral activity. The instantaneous inhibitory potential (IIP), the log reduction in infectivity in a single round assay at clinical drug concentrations, has been proposed as a novel index for comparing antiviral activity. Summary Among in vitro measures of antiviral activity, single round infection assays have the advantage of measure instantaneous inhibition by a drug. Re-evaluating the antiviral activity of approved HIV-1 drugs has shown that the slope parameter is an important factor in drug activity. Determining the IIP by using a single round infectivity assay may provide important insights that can predict the in vivo efficacy of anti-HIV-1 drugs. PMID:19841584

  16. In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

    Science.gov (United States)

    Wargo, Andrew R.; Kurath, Gael

    2011-01-01

    The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

  17. Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

    Science.gov (United States)

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Sicard, Didier; Salmon, Dominique; Delfraissy, Jean-Francois; Venet, Alain; Sinet, Martine; Guillet, Jean-Gerard

    1999-01-01

    The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment. PMID:10438796

  18. IL-15 STIMULATED NATURAL KILLER CELLS CLEAR HIV-1 INFECTED CELLS FOLLOWING LATENCY REVERSAL EX VIVO.

    Science.gov (United States)

    Garrido, Carolina; Abad-Fernandez, Maria; Tuyishime, Marina; Pollara, Justin J; Ferrari, Guido; Soriano-Sarabia, Natalia; Margolis, David M

    2018-03-28

    Current efforts towards HIV eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8 + T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of IL-15 treatment on NK cell function and the potential of stimulated NK cells to clear the HIV reservoir. We measured NK cell receptor expression, antibody-dependent cell-dependent cytotoxicity (ADCC), cytotoxicity, IFN-γ production and antiviral activity in autologous HIV replication systems. All NK cell functions were uniformly improved by IL-15, and more importantly, IL-15-treated NK cells were able to clear latently HIV infected cells after exposure to vorinostat, a clinically relevant latency reversing agent. We also demonstrate that NK cells from HIV infected individuals aviremic on antiretroviral therapy can be efficiently stimulated with IL-15. Our work opens a promising line of investigation towards future immunotherapies to clear persistent HIV infection using NK cells. IMPORTANCE In the search for an HIV cure, strategies to enhance immune function to allow recognition and clearance of HIV infected cells following latency reversal are being evaluated. Natural killer (NK) cells possess characteristics that can be exploited for immunotherapy against persistent HIV infection. We demonstrate that NK cells from HIV-positive donors can be strongly stimulated with IL-15, improving their antiviral and cytotoxic potential, and more importantly, clearing HIV infected cells after latency reversal with a clinically relevant drug. Our results encourage further investigation to design NK cell-based immunotherapies to achieve HIV eradication. Copyright © 2018 American Society for Microbiology.

  19. Host-Derived Sialic Acids Are an Important Nutrient Source Required for Optimal Bacterial Fitness In Vivo.

    Science.gov (United States)

    McDonald, Nathan D; Lubin, Jean-Bernard; Chowdhury, Nityananda; Boyd, E Fidelma

    2016-04-12

    A major challenge facing bacterial intestinal pathogens is competition for nutrient sources with the host microbiota.Vibrio cholerae is an intestinal pathogen that causes cholera, which affects millions each year; however, our knowledge of its nutritional requirements in the intestinal milieu is limited. In this study, we demonstrated that V. cholerae can grow efficiently on intestinal mucus and its component sialic acids and that a tripartite ATP-independent periplasmic SiaPQM strain, transporter-deficient mutant NC1777, was attenuated for colonization using a streptomycin-pretreated adult mouse model. In in vivo competition assays, NC1777 was significantly outcompeted for up to 3 days postinfection. NC1777 was also significantly outcompeted in in vitro competition assays in M9 minimal medium supplemented with intestinal mucus, indicating that sialic acid uptake is essential for fitness. Phylogenetic analyses demonstrated that the ability to utilize sialic acid was distributed among 452 bacterial species from eight phyla. The majority of species belonged to four phyla, Actinobacteria (members of Actinobacillus, Corynebacterium, Mycoplasma, and Streptomyces), Bacteroidetes (mainly Bacteroides, Capnocytophaga, and Prevotella), Firmicutes (members of Streptococcus, Staphylococcus, Clostridium, and Lactobacillus), and Proteobacteria (including Escherichia, Shigella, Salmonella, Citrobacter, Haemophilus, Klebsiella, Pasteurella, Photobacterium, Vibrio, and Yersinia species), mostly commensals and/or pathogens. Overall, our data demonstrate that the ability to take up host-derived sugars and sialic acid specifically allows V. cholerae a competitive advantage in intestinal colonization and that this is a trait that is sporadic in its occurrence and phylogenetic distribution and ancestral in some genera but horizontally acquired in others. Sialic acids are nine carbon amino sugars that are abundant on all mucous surfaces. The deadly human pathogen Vibrio cholerae contains

  20. Host-Derived Sialic Acids Are an Important Nutrient Source Required for Optimal Bacterial Fitness In Vivo

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    Nathan D. McDonald

    2016-04-01

    Full Text Available A major challenge facing bacterial intestinal pathogens is competition for nutrient sources with the host microbiota. Vibrio cholerae is an intestinal pathogen that causes cholera, which affects millions each year; however, our knowledge of its nutritional requirements in the intestinal milieu is limited. In this study, we demonstrated that V. cholerae can grow efficiently on intestinal mucus and its component sialic acids and that a tripartite ATP-independent periplasmic SiaPQM strain, transporter-deficient mutant NC1777, was attenuated for colonization using a streptomycin-pretreated adult mouse model. In in vivo competition assays, NC1777 was significantly outcompeted for up to 3 days postinfection. NC1777 was also significantly outcompeted in in vitro competition assays in M9 minimal medium supplemented with intestinal mucus, indicating that sialic acid uptake is essential for fitness. Phylogenetic analyses demonstrated that the ability to utilize sialic acid was distributed among 452 bacterial species from eight phyla. The majority of species belonged to four phyla, Actinobacteria (members of Actinobacillus, Corynebacterium, Mycoplasma, and Streptomyces, Bacteroidetes (mainly Bacteroides, Capnocytophaga, and Prevotella, Firmicutes (members of Streptococcus, Staphylococcus, Clostridium, and Lactobacillus, and Proteobacteria (including Escherichia, Shigella, Salmonella, Citrobacter, Haemophilus, Klebsiella, Pasteurella, Photobacterium, Vibrio, and Yersinia species, mostly commensals and/or pathogens. Overall, our data demonstrate that the ability to take up host-derived sugars and sialic acid specifically allows V. cholerae a competitive advantage in intestinal colonization and that this is a trait that is sporadic in its occurrence and phylogenetic distribution and ancestral in some genera but horizontally acquired in others.

  1. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

    Science.gov (United States)

    Scarlatti, G; Tresoldi, E; Björndal, A; Fredriksson, R; Colognesi, C; Deng, H K; Malnati, M S; Plebani, A; Siccardi, A G; Littman, D R; Fenyö, E M; Lusso, P

    1997-11-01

    of gp120 were associated with the loss of sensitivity to C-C chemokines and the shift in co-receptor usage. These results suggest an adaptive evolution of HIV-1 in vivo, leading to escape from the control of the antiviral C-C chemokines.

  2. Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

    Science.gov (United States)

    Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

    2017-11-01

    3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries.

    Directory of Open Access Journals (Sweden)

    David Skurnik

    Full Text Available High-throughput sequencing of transposon (Tn libraries created within entire genomes identifies and quantifies the contribution of individual genes and operons to the fitness of organisms in different environments. We used insertion-sequencing (INSeq to analyze the contribution to fitness of all non-essential genes in the chromosome of Pseudomonas aeruginosa strain PA14 based on a library of ∼300,000 individual Tn insertions. In vitro growth in LB provided a baseline for comparison with the survival of the Tn insertion strains following 6 days of colonization of the murine gastrointestinal tract as well as a comparison with Tn-inserts subsequently able to systemically disseminate to the spleen following induction of neutropenia. Sequencing was performed following DNA extraction from the recovered bacteria, digestion with the MmeI restriction enzyme that hydrolyzes DNA 16 bp away from the end of the Tn insert, and fractionation into oligonucleotides of 1,200-1,500 bp that were prepared for high-throughput sequencing. Changes in frequency of Tn inserts into the P. aeruginosa genome were used to quantify in vivo fitness resulting from loss of a gene. 636 genes had <10 sequencing reads in LB, thus defined as unable to grow in this medium. During in vivo infection there were major losses of strains with Tn inserts in almost all known virulence factors, as well as respiration, energy utilization, ion pumps, nutritional genes and prophages. Many new candidates for virulence factors were also identified. There were consistent changes in the recovery of Tn inserts in genes within most operons and Tn insertions into some genes enhanced in vivo fitness. Strikingly, 90% of the non-essential genes were required for in vivo survival following systemic dissemination during neutropenia. These experiments resulted in the identification of the P. aeruginosa strain PA14 genes necessary for optimal survival in the mucosal and systemic environments of a mammalian

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

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    Sandhya Boyapalle

    Full Text Available 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.

  5. Assessment of Integration-defective HIV-1 and EIAV Vectors In Vitro and In Vivo

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    Scott Ellis

    2012-01-01

    Full Text Available The interest in integrase-defective lentiviral vectors (IDLVs stems from their potential advantage of large cloning capacity and broad cell tropism while avoiding the possibility of insertional mutagenesis. Here, we directly compared the transducing potential of IDLVs based on the equine infectious anemia virus (EIAV to the more commonly described HIV-1 IDLVs. IDLVs were constructed by introducing equivalent single/triple mutations into the integrase catalytic triad. We show that both the single and the triple mutant HIV-1 IDLVs transduce the PC12 cells, but not the C2C12 cells, with similar efficiency to their parental HIV-1 vector. In contrast, the single and triple EIAV IDLVs did not efficiently transduce either differentiated cell line. Moreover, this HIV-1 IDLV-mediated expression was independent of any residual integration activity because reporter expression was lost when cell cycling was restored. Four weeks following stereotactic administration into adult rat brains, only the single HIV-1 IDLV mutant displayed a comparable transduction profile to the parental HIV-1 vector. In contrast, neither EIAV IDLV mutants showed significant reporter gene expression. This work indicates that the transducing potential of IDLVs appears to depend not only on the choice of integrase mutation and type of target cell, but also on the nature of the lentiviral vector.

  6. A new general method for simultaneous fitting of temperature and concentration dependence of reaction rates yields kinetic and thermodynamic parameters for HIV reverse transcriptase specificity.

    Science.gov (United States)

    Li, An; Ziehr, Jessica L; Johnson, Kenneth A

    2017-04-21

    Recent studies have demonstrated the dominant role of induced fit in enzyme specificity of HIV reverse transcriptase and many other enzymes. However, relevant thermodynamic parameters are lacking, and equilibrium thermodynamic methods are of no avail because the key parameters can only be determined by kinetic measurement. By modifying KinTek Explorer software, we present a new general method for globally fitting data collected over a range of substrate concentrations and temperatures and apply it to HIV reverse transcriptase. Fluorescence stopped-flow methods were used to record the kinetics of enzyme conformational changes that monitor nucleotide binding and incorporation. The nucleotide concentration dependence was measured at temperatures ranging from 5 to 37 °C, and the raw data were fit globally to derive a single set of rate constants at 37 °C and a set of activation enthalpy terms to account for the kinetics at all other temperatures. This comprehensive analysis afforded thermodynamic parameters for nucleotide binding ( K d , Δ G , Δ H , and Δ S at 37 °C) and kinetic parameters for enzyme conformational changes and chemistry (rate constants and activation enthalpy). Comparisons between wild-type enzyme and a mutant resistant to nucleoside analogs used to treat HIV infections reveal that the ground state binding is weaker and the activation enthalpy for the conformational change step is significantly larger for the mutant. Further studies to explore the structural underpinnings of the observed thermodynamics and kinetics of the conformational change step may help to design better analogs to treat HIV infections and other diseases. Our new method is generally applicable to enzyme and chemical kinetics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Proviral HIV-genome-wide and pol-gene specific zinc finger nucleases: usability for targeted HIV gene therapy.

    Science.gov (United States)

    Wayengera, Misaki

    2011-07-22

    Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases) AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively). However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX) at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i) to assemble and construct zinc finger arrays and nucleases (ZFN) with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii) to advance a model for pre-clinically testing lentiviral vectors (LV) that deliver and transduce either ZFN genotype. First, we computationally generated the consensus sequences of (a) 114 dsDNA-binding zinc finger (Zif) arrays (ZFAs or ZifHIV-pol) and (b) two zinc-finger nucleases (ZFNs) which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN). Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN). Second, a model for constructing lentiviral vectors (LVs) that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively) is proposed. Third, two preclinical models for controlled testing of the safety and efficacy of either of these

  8. Distinguishing HIV-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples

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    Lee Christopher

    2006-05-01

    Full Text Available Abstract Background HIV can evolve drug resistance rapidly in response to new drug treatments, often through a combination of multiple mutations 123. It would be useful to develop automated analyses of HIV sequence polymorphism that are able to predict drug resistance mutations, and to distinguish different types of functional roles among such mutations, for example, those that directly cause drug resistance, versus those that play an accessory role. Detecting functional interactions between mutations is essential for this classification. We have adapted a well-known measure of evolutionary selection pressure (Ka/Ks and developed a conditional Ka/Ks approach to detect important interactions. Results We have applied this analysis to four independent HIV protease sequencing datasets: 50,000 clinical samples sequenced by Specialty Laboratories, Inc.; 1800 samples from patients treated with protease inhibitors; 2600 samples from untreated patients; 400 samples from untreated African patients. We have identified 428 mutation interactions in Specialty dataset with statistical significance and we were able to distinguish primary vs. accessory mutations for many well-studied examples. Amino acid interactions identified by conditional Ka/Ks matched 80 of 92 pair wise interactions found by a completely independent study of HIV protease (p-value for this match is significant: 10-70. Furthermore, Ka/Ks selection pressure results were highly reproducible among these independent datasets, both qualitatively and quantitatively, suggesting that they are detecting real drug-resistance and viral fitness mutations in the wild HIV-1 population. Conclusion Conditional Ka/Ks analysis can detect mutation interactions and distinguish primary vs. accessory mutations in HIV-1. Ka/Ks analysis of treated vs. untreated patient data can distinguish drug-resistance vs. viral fitness mutations. Verification of these results would require longitudinal studies. The result

  9. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

    Science.gov (United States)

    Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

    2016-03-03

    The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

  10. Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

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    Xudong Lin

    Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

  11. CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

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    Nadia T Sebastian

    2017-07-01

    Full Text Available Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.

  12. CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

    Science.gov (United States)

    Sebastian, Nadia T; Zaikos, Thomas D; Terry, Valeri; Taschuk, Frances; McNamara, Lucy A; Onafuwa-Nuga, Adewunmi; Yucha, Ryan; Signer, Robert A J; Riddell, James; Bixby, Dale; Markowitz, Norman; Morrison, Sean J; Collins, Kathleen L

    2017-07-01

    Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.

  13. On modeling HIV and T cells in vivo: assessing causal estimators in vaccine trials.

    Directory of Open Access Journals (Sweden)

    W David Wick

    2006-06-01

    Full Text Available The first efficacy trials--named STEP--of a T cell vaccine against HIV/AIDS began in 2004. The unprecedented structure of these trials raised new modeling and statistical challenges. Is it plausible that memory T cells, as opposed to antibodies, can actually prevent infection? If they fail at prevention, to what extent can they ameliorate disease? And how do we estimate efficacy in a vaccine trial with two primary endpoints, one traditional, one entirely novel (viral load after infection, and where the latter may be influenced by selection bias due to the former? In preparation for the STEP trials, biostatisticians developed novel techniques for estimating a causal effect of a vaccine on viral load, while accounting for post-randomization selection bias. But these techniques have not been tested in biologically plausible scenarios. We introduce new stochastic models of T cell and HIV kinetics, making use of new estimates of the rate that cytotoxic T lymphocytes--CTLs; the so-called killer T cells--can kill HIV-infected cells. Based on these models, we make the surprising discovery that it is not entirely implausible that HIV-specific CTLs might prevent infection--as the designers explicitly acknowledged when they chose the endpoints of the STEP trials. By simulating thousands of trials, we demonstrate that the new statistical methods can correctly identify an efficacious vaccine, while protecting against a false conclusion that the vaccine exacerbates disease. In addition to uncovering a surprising immunological scenario, our results illustrate the utility of mechanistic modeling in biostatistics.

  14. One size does not fit all: HIV testing preferences differ among high-risk groups in Northern Tanzania.

    Science.gov (United States)

    Ostermann, Jan; Njau, Bernard; Mtuy, Tara; Brown, Derek S; Mühlbacher, Axel; Thielman, Nathan

    2015-01-01

    In order to maximize the effectiveness of "Seek, Test, and Treat" strategies for curbing the HIV epidemic, new approaches are needed to increase the uptake of HIV testing services, particularly among high-risk groups. Low HIV testing rates among such groups suggest that current testing services may not align well with the testing preferences of these populations. Female bar workers and male mountain porters have been identified as two important high-risk groups in the Kilimanjaro Region of Tanzania. We used conventional survey methods and a discrete choice experiment (DCE), a preference elicitation method increasingly applied by economists and policy-makers to inform health policy and services, to analyze trade-offs made by individuals and quantify preferences for HIV testing services. Bivariate descriptive statistics were used to analyze differences in survey responses across groups. Compared to 486 randomly selected community members, 162 female bar workers and 194 male Kilimanjaro porters reported 2-3 times as many lifetime sexual partners (p porters preferred testing in venues where antiretroviral therapy was readily available. Both high-risk groups were less averse to traveling longer distances to test compared to their community counterparts. These results expose systematic differences in HIV testing preferences across high-risk populations compared to their community peers. Tailoring testing options to the preferences of high-risk populations should be evaluated as a means of improving uptake of testing in these populations.

  15. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    landscapes (nelfinavir [NFV] and zidovudine [AZT] plus lamivudine [3TC]) to predict week 12 viral load (VL) change for 176 treatment change episodes (TCEs) and probability of week 48 virological failure for 90 TCEs, in treatment experienced patients starting these drugs in combination. RESULTS: A higher...

  16. Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.

    Science.gov (United States)

    Caizhen, Guo; Yan, Gao; Ronron, Chang; Lirong, Yang; Panpan, Chu; Xuemei, Hu; Yuanbiao, Qiao; Qingshan, Li

    2015-04-10

    An essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78 nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7 Å to 7.4 and 7.9 nm, respectively. In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24 mg/kg bw in NIH/KM/ICR mice. The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Littman Dan R

    2009-01-01

    Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

  18. The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Akerblom, L; Heegaard, P M

    1995-01-01

    The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates...... to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding...... to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding...

  19. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Directory of Open Access Journals (Sweden)

    Danushka K Wijesundara

    Full Text Available Qualitative characteristics of cytotoxic CD8+ T cells (CTLs are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV-HIV prime followed by a recombinant vaccinia virus (VV-HIV booster were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold, to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  20. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Ranasinghe, Charani; Jackson, Ronald J; Lidbury, Brett A; Parish, Christopher R; Quah, Benjamin J C

    2014-01-01

    Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  1. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  2. Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to in vivo success

    CSIR Research Space (South Africa)

    Pillay, V

    2012-06-01

    Full Text Available employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide...

  3. In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae

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    Leah R. Vincent

    2018-04-01

    Full Text Available Resistance to ceftriaxone in Neisseria gonorrhoeae is mainly conferred by mosaic penA alleles that encode penicillin-binding protein 2 (PBP2 variants with markedly lower rates of acylation by ceftriaxone. To assess the impact of these mosaic penA alleles on gonococcal fitness, we introduced the mosaic penA alleles from two ceftriaxone-resistant (Cror clinical isolates (H041 and F89 into a Cros strain (FA19 by allelic exchange and showed that the resultant Cror mutants were significantly outcompeted by the Cros parent strain in vitro and in a murine infection model. Four Cror compensatory mutants of FA19 penA41 were isolated independently from mice that outcompeted the parent strain both in vitro and in vivo. One of these compensatory mutants (LV41C displayed a unique growth profile, with rapid log growth followed by a sharp plateau/gradual decline at stationary phase. Genome sequencing of LV41C revealed a mutation (G348D in the acnB gene encoding the bifunctional aconitate hydratase 2/2 methylisocitrate dehydratase. Introduction of the acnBG348D allele into FA19 penA41 conferred both a growth profile that phenocopied that of LV41C and a fitness advantage, although not as strongly as that exhibited by the original compensatory mutant, suggesting the existence of additional compensatory mutations. The mutant aconitase appears to be a functional knockout with lower activity and expression than wild-type aconitase. Transcriptome sequencing (RNA-seq analysis of FA19 penA41 acnBG348D revealed a large set of upregulated genes involved in carbon and energy metabolism. We conclude that compensatory mutations can be selected in Cror gonococcal strains that increase metabolism to ameliorate their fitness deficit.

  4. In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Vincent, Leah R; Kerr, Samuel R; Tan, Yang; Tomberg, Joshua; Raterman, Erica L; Dunning Hotopp, Julie C; Unemo, Magnus; Nicholas, Robert A; Jerse, Ann E

    2018-04-03

    Resistance to ceftriaxone in Neisseria gonorrhoeae is mainly conferred by mosaic penA alleles that encode penicillin-binding protein 2 (PBP2) variants with markedly lower rates of acylation by ceftriaxone. To assess the impact of these mosaic penA alleles on gonococcal fitness, we introduced the mosaic penA alleles from two ceftriaxone-resistant (Cro r ) clinical isolates (H041 and F89) into a Cro s strain (FA19) by allelic exchange and showed that the resultant Cro r mutants were significantly outcompeted by the Cro s parent strain in vitro and in a murine infection model. Four Cro r compensatory mutants of FA19 penA41 were isolated independently from mice that outcompeted the parent strain both in vitro and in vivo One of these compensatory mutants (LV41C) displayed a unique growth profile, with rapid log growth followed by a sharp plateau/gradual decline at stationary phase. Genome sequencing of LV41C revealed a mutation (G348D) in the acnB gene encoding the bifunctional aconitate hydratase 2/2 methylisocitrate dehydratase. Introduction of the acnB G348D allele into FA19 penA41 conferred both a growth profile that phenocopied that of LV41C and a fitness advantage, although not as strongly as that exhibited by the original compensatory mutant, suggesting the existence of additional compensatory mutations. The mutant aconitase appears to be a functional knockout with lower activity and expression than wild-type aconitase. Transcriptome sequencing (RNA-seq) analysis of FA19 penA41 acnB G348D revealed a large set of upregulated genes involved in carbon and energy metabolism. We conclude that compensatory mutations can be selected in Cro r gonococcal strains that increase metabolism to ameliorate their fitness deficit. IMPORTANCE The emergence of ceftriaxone-resistant (Cro r ) Neisseria gonorrhoeae has led to the looming threat of untreatable gonorrhea. Whether Cro resistance is likely to spread can be predicted from studies that compare the relative fitnesses of

  5. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Denis Hélène

    2008-12-01

    Full Text Available Abstract Background In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells in situ. Results The overall prostate characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4IIIB strain and a primary R5X4 strain showed less efficient replication in this organ. Conclusion The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.

  6. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  7. Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses

    NARCIS (Netherlands)

    I. Deuzing (Ilona); C. Charpentier (Charlotte); D.J. Wright (David Justin); S. Matheron (Sophie); J. Paton (Jack); D. Frentz (Dineke); D.A.M.C. van de Vijver (David); P.V. Coveney (Peter); D. Descamps (Diane); C.A.B. Boucher (Charles); N. Beerens (Nancy)

    2015-01-01

    textabstractInfection with HIV-2 can ultimately lead to AIDS, although disease progression is much slower than with HIV-1. HIV-2 patients are mostly treated with a combination of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and protease inhibitors designed for HIV-1. Many studies have

  8. Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available CD4(+ T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+ cells, and (ii that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+ compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+ T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p and disappearance (d* rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul participated. CCR5-expression defined a CD4(+ subpopulation of predominantly CD45R0(+ memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+ vs CCR5(-; healthy controls; P<0.01. Conversely, CXCR4 expression defined CD4(+ T-cells (predominantly CD45RA(+ naive cells with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+CD45R0(+CD4(+ memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05, naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9 or X4-tropic (n = 4. Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively. Our data are most consistent with models in which CD4(+ T-cell loss is primarily driven by non-specific immune activation.

  9. A cooperative interaction between nontranslated RNA sequences and NS5A protein promotes in vivo fitness of a chimeric hepatitis C/GB virus B.

    Directory of Open Access Journals (Sweden)

    Lucile Warter

    Full Text Available GB virus B (GBV-B is closely related to hepatitis C virus (HCV, infects small non-human primates, and is thus a valuable surrogate for studying HCV. Despite significant differences, the 5' nontranslated RNAs (NTRs of these viruses fold into four similar structured domains (I-IV, with domains II-III-IV comprising the viral internal ribosomal entry site (IRES. We previously reported the in vivo rescue of a chimeric GBV-B (vGB/III(HC containing HCV sequence in domain III, an essential segment of the IRES. We show here that three mutations identified within the vGB/III(HC genome (within the 3'NTR, upstream of the poly(U tract, and NS5A coding sequence are necessary and sufficient for production of this chimeric virus following intrahepatic inoculation of synthetic RNA in tamarins, and thus apparently compensate for the presence of HCV sequence in domain III. To assess the mechanism(s underlying these compensatory mutations, and to determine whether 5'NTR subdomains participating in genome replication do so in a virus-specific fashion, we constructed and evaluated a series of chimeric subgenomic GBV-B replicons in which various 5'NTR subdomains were substituted with their HCV homologs. Domains I and II of the GBV-B 5'NTR could not be replaced with HCV sequence, indicating that they contain essential, virus-specific RNA replication elements. In contrast, domain III could be swapped with minimal loss of genome replication capacity in cell culture. The 3'NTR and NS5A mutations required for rescue of the related chimeric virus in vivo had no effect on replication of the subgenomic GBneoD/III(HC RNA in vitro. The data suggest that in vivo fitness of the domain III chimeric virus is dependent on a cooperative interaction between the 5'NTR, 3'NTR and NS5A at a step in the viral life cycle subsequent to genome replication, most likely during particle assembly. Such a mechanism may be common to all hepaciviruses.

  10. L-Chicoric acid inhibits human immunodeficiency virus type 1 integration in vivo and is a noncompetitive but reversible inhibitor of HIV-1 integrase in vitro

    International Nuclear Information System (INIS)

    Reinke, Ryan A.; Lee, Deborah J.; McDougall, Brenda R.; King, Peter J.; Victoria, Joseph; Mao Yingqun; Lei Xiangyang; Reinecke, Manfred G.; Robinson, W. Edward

    2004-01-01

    The human immunodeficiency virus (HIV) integrase (IN) must covalently join the viral cDNA into a host chromosome for productive HIV infection. L-Chicoric acid (L-CA) enters cells poorly but is a potent inhibitor of IN in vitro. Using quantitative real-time polymerase chain reaction (PCR), L-CA inhibits integration at concentrations from 500 nM to 10 μM but also inhibits entry at concentrations above 1 μM. Using recombinant HIV IN, steady-state kinetic analyses with L-CA were consistent with a noncompetitive or irreversible mechanism of inhibition. IN, in the presence or absence of L-CA, was successively washed. Inhibition of IN diminished, demonstrating that L-CA was reversibly bound to the protein. These data demonstrate that L-CA is a noncompetitive but reversible inhibitor of IN in vitro and of HIV integration in vivo. Thus, L-CA likely interacts with amino acids other than those which bind substrate

  11. An In Vivo Evaluation of the Fit of Zirconium-Oxide Based, Ceramic Single Crowns with Vertical and Horizontal Finish Line Preparations.

    Science.gov (United States)

    Vigolo, Paolo; Mutinelli, Sabrina; Biscaro, Leonello; Stellini, Edoardo

    2015-12-01

    Different types of tooth preparations influence the marginal precision of zirconium-oxide based ceramic single crowns. In this in vivo study, the marginal fits of zirconium-oxide based ceramic single crowns with vertical and horizontal finish lines were compared. Forty-six teeth were chosen in eight patients indicated for extraction for implant placement. CAD/CAM technology was used for the production of 46 zirconium-oxide-based ceramic single crowns: 23 teeth were prepared with vertical finishing lines, 23 with horizontal finishing lines. One operator accomplished all clinical procedures. The zirconia crowns were cemented with glass ionomer cement. The teeth were extracted 1 month later. Marginal gaps along vertical planes were measured for each crown, using a total of four landmarks for each tooth by means of a microscope at 50× magnification. On conclusion of microscopic assessment, ESEM evaluation was completed on all specimens. The comparison of the gap between the two types of preparation was performed with a nonparametric test (two-sample Wilcoxon rank-sum test) with a level of significance fixed at p zirconium-oxide-based ceramic CAD/CAM crowns with vertical and horizontal finish line preparations were not different. © 2015 by the American College of Prosthodontists.

  12. The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Akerblom, L; Heegaard, P M

    1995-01-01

    The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates...... patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3...... to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding...

  13. Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss.

    Directory of Open Access Journals (Sweden)

    Elisabeth Dam

    2009-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 resistance to protease inhibitors (PI results from mutations in the viral protease (PR that reduce PI binding but also decrease viral replicative capacity (RC. Additional mutations compensating for the RC loss subsequently accumulate within PR and in Gag substrate cleavage sites. We examined the respective contribution of mutations in PR and Gag to PI resistance and RC and their interdependence using a panel of HIV-1 molecular clones carrying different sequences from six patients who had failed multiple lines of treatment. Mutations in Gag strongly and directly contributed to PI resistance besides compensating for fitness loss. This effect was essentially carried by the C-terminal region of Gag (containing NC-SP2-p6 with little or no contribution from MA, CA, and SP1. The effect of Gag on resistance depended on the presence of cleavage site mutations A431V or I437V in NC-SP2-p6 and correlated with processing of the NC/SP2 cleavage site. By contrast, reverting the A431V or I437V mutation in these highly evolved sequences had little effect on RC. Mutations in the NC-SP2-p6 region of Gag can be dually selected as compensatory and as direct PI resistance mutations, with cleavage at the NC-SP2 site behaving as a rate-limiting step in PI resistance. Further compensatory mutations render viral RC independent of the A431V or I437V mutations while their effect on resistance persists.

  14. Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

    Science.gov (United States)

    Pillay, Viness; Mashingaidze, Felix; Choonara, Yahya E; Du Toit, Lisa C; Buchmann, Eckhart; Maharaj, Vinesh; Ndesendo, Valence M K; Kumar, Pradeep

    2012-06-01

    The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately. Copyright © 2012 Wiley Periodicals, Inc.

  15. The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

    Directory of Open Access Journals (Sweden)

    Malcolm A West

    Full Text Available In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1, and the post-exercise phosphocreatine recovery rate constant (min-1, a measure of muscle mitochondrial capacity in vivo.Median age was 67 years (IQR 64-75. Differences (95%CI in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9, p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1, p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17, p<0.001.The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery.Clinicaltrials.gov registration NCT01859442.

  16. Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2011-07-01

    Full Text Available Abstract Background Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively. However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i to assemble and construct zinc finger arrays and nucleases (ZFN with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii to advance a model for pre-clinically testing lentiviral vectors (LV that deliver and transduce either ZFN genotype. Methods and Results First, we computationally generated the consensus sequences of (a 114 dsDNA-binding zinc finger (Zif arrays (ZFAs or ZifHIV-pol and (b two zinc-finger nucleases (ZFNs which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN. Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN. Second, a model for constructing lentiviral vectors (LVs that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively is proposed. Third, two preclinical models for controlled testing of

  17. In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

    Science.gov (United States)

    Ndesendo, Valence M K; Choonara, Yahya E; Meyer, Leith C R; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2015-01-01

    The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

  18. Localized or Systemic {italic In Vivo} Heat-Inactivation of Human Immunodeficiency Virus (HIV): A Mathematical Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pennypacker, Carl R.; Perelson, A.S.; Nys, N.; Nelson, G.; Sessler, D.I.

    1993-12-15

    Temperatures as low as 42 C, maintained for a little as 25 minutes, inactivate {approx}25% of HIV. Furthermore, human immunodeficiency virus (HIV)-infected T-cells are more sensitive to heat than healthy lymphocytes and susceptibility increases when the cells are pre-sensitized by exposure to tumor necrosis factor. Thus, induction of a whole-body hyperthermia, or hyperthermia specifically limited to tissues having a high viral load, are potential antiviral therapies for acquired immunodeficiency disease (AIDS). Accordingly, we incorporated therapeutic hyperthermia into an existing mathematical model which evaluates the interaction between HIV and CD4{sup +} T cells. Given the assumptions and limitations of this model, the results indicate that a daily therapy, reducing the population of actively infected cells by 40% or infectious virus by 50%, would effectively reverse the depletion of T cells. In contrast, a daily reduction of 20% of either actively infected cells or infectious virus would have a marginal effect. However, reduction by 20% of both actively infected cells and infectious virus could restore T cell numbers, assuming that permanent damage had not been inflicted on the thymus. Whole-body hyperthermia seems unlikely to be clinically useful, unless it can be induced non-invasively without general anesthesia. In contrast, heating directed specifically to areas of viral concentration may be effective and have a suitable risk/benefit ratio.

  19. Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells.

    Directory of Open Access Journals (Sweden)

    John K Bui

    2017-02-01

    Full Text Available The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART with PMA/ionomycin (day 1-7, followed by rest (day 7-21, and then repeat stimulation (day 21-28, always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication. HIV DNA and virion RNA in the supernatant were quantified by qPCR. Single genome sequencing (SGS of p6-PR-RT was performed to genetically characterize proviruses and virion-associated genomic RNA. The replication-competence of the virions produced was determined by the viral outgrowth assay (VOA and SGS of co-culture supernatants from multiple time points. Experiments were performed with purified CD4+ T-cells from five consecutively recruited donors who had been on suppressive ART for > 2 years. In all experiments, HIV RNA levels in supernatant increased following initial stimulation, decreased or remained stable during the rest period, and increased again with repeat stimulation. HIV DNA levels did not show a consistent pattern of change. SGS of proviruses revealed diverse outcomes of infected cell populations, ranging from their apparent elimination to persistence and expansion. Importantly, a subset of infected cells expanded and produced infectious virus continuously after stimulation. These findings underscore the complexity of eliminating reservoirs of HIV-infected cells and highlight the need for new strategies to kill HIV-infected cells before they can proliferate.

  20. A One-Size-Fits-All HIV Prevention and Education Approach?: Interpreting Divergent HIV Risk Perceptions Between African American and East African Immigrant Women in Washington, DC Using the Proximate-Determinants Conceptual Framework.

    Science.gov (United States)

    De Jesus, Maria; Taylor, Juanita; Maine, Cathleen; Nalls, Patricia

    2016-02-01

    To date, there are very few comparative US studies and none in DC that distinguish between US-born and foreign-born black women to examine and compare their perceptions of HIV risk. This qualitative study, therefore, analyzes African American and East African women's perceptions of HIV risk in the Washington DC Metropolitan area, which has the highest AIDS rate in the United States. Forty in-depth, semistructured interviews and 10 cognitive interviews were conducted among a sample of 25 African American women and 25 East African born women between October 2012 and March 2013 to examine perceptions regarding HIV risk. The in-depth semistructured interviews were preceded by the cognitive interviews and accompanying survey. Study protocol was reviewed and approved by the American University Institutional Review Board. Adopting Boerma and Weir's Proximate Determinants conceptual framework to interpret the data, the results of the study demonstrate that African American and East African immigrant women have divergent perceptions of HIV risk. Although African American women ascribe HIV risk to individual-level behaviors and choices such as unprotected sex, East African women attribute HIV risk to conditions of poverty and survival. Study findings suggest that addressing HIV prevention and education among black women in DC will require distinct and targeted strategies that are culturally and community-centered to resonate with these different audiences.

  1. A one-size-fits-all HIV prevention and education approach?: Analyzing and interpreting divergent HIV risk perceptions between African American and East African immigrant women in Washington, DC

    Science.gov (United States)

    De Jesus, Maria; Taylor, Juanita; Maine, Cathleen; Nalls, Patricia

    2015-01-01

    Background To date, there are very few comparative US studies and none in DC that distinguish between US-born and foreign-born Black women to examine and compare their perceptions of HIV risk. This qualitative study, therefore, analyzes African American and East African women’s perceptions of HIV risk in the Washington DC Metropolitan area, which has the highest AIDS rate in the US. Methods Forty in-depth, semi-structured interviews and 10 cognitive interviews were conducted among a sample of 25 African American women and 25 East African born women between October 2012 and March 2013 to examine perceptions regarding HIV risk. The in-depth semi-structured interviews were preceded by the cognitive interviews and accompanying survey. Study protocol was reviewed and approved by the American University Institutional Review Board. Results Adopting Boerma and Weir’s Proximate Determinants conceptual framework to interpret the data, the results of the study demonstrate that African American and East African immigrant women have divergent perceptions of HIV risk. While African American women ascribe HIV risk to individual-level behaviors and choices such as unprotected sex, East African women attribute HIV risk to conditions of poverty and survival. Conclusions Study findings suggest that addressing HIV prevention and education among Black women in DC will require distinct and targeted strategies that are culturally and community-centered in order to resonate with these different audiences. PMID:26766523

  2. Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

    Science.gov (United States)

    Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

    2014-03-01

    A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is 350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P vs 9.8%, P decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

  3. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

    Science.gov (United States)

    Strizki, J M; Xu, S; Wagner, N E; Wojcik, L; Liu, J; Hou, Y; Endres, M; Palani, A; Shapiro, S; Clader, J W; Greenlee, W J; Tagat, J R; McCombie, S; Cox, K; Fawzi, A B; Chou, C C; Pugliese-Sivo, C; Davies, L; Moreno, M E; Ho, D D; Trkola, A; Stoddart, C A; Moore, J P; Reyes, G R; Baroudy, B M

    2001-10-23

    We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

  4. Fitness club

    CERN Multimedia

    Fitness club

    2011-01-01

    General fitness Classes Enrolments are open for general fitness classes at CERN taking place on Monday, Wednesday, and Friday lunchtimes in the Pump Hall (building 216). There are shower facilities for both men and women. It is possible to pay for 1, 2 or 3 classes per week for a minimum of 1 month and up to 6 months. Check out our rates and enrol at: http://cern.ch/club-fitness Hope to see you among us! CERN Fitness Club fitness.club@cern.ch  

  5. Correlation of results obtained by in-vivo optical spectroscopy with measured blood oxygen saturation using a positive linear regression fit

    Science.gov (United States)

    McCormick, Patrick W.; Lewis, Gary D.; Dujovny, Manuel; Ausman, James I.; Stewart, Mick; Widman, Ronald A.

    1992-05-01

    Near infrared light generated by specialized instrumentation was passed through artificially oxygenated human blood during simultaneous sampling by a co-oximeter. Characteristic absorption spectra were analyzed to calculate the ratio of oxygenated to reduced hemoglobin. A positive linear regression fit between diffuse transmission oximetry and measured blood oxygenation over the range 23% to 99% (r2 equals .98, p signal was observed in the patient over time. The procedure was able to be performed clinically without difficulty; rSO2 values recorded continuously demonstrate the usefulness of the technique. Using the same instrumentation, arterial input and cerebral response functions, generated by IV tracer bolus, were deconvoluted to measure mean cerebral transit time. Date collected over time provided a sensitive index of changes in cerebral blood flow as a result of therapeutic maneuvers.

  6. Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics.

    Science.gov (United States)

    Peacock, Thomas P; Benton, Donald J; James, Joe; Sadeyen, Jean-Remy; Chang, Pengxiang; Sealy, Joshua E; Bryant, Juliet E; Martin, Stephen R; Shelton, Holly; Barclay, Wendy S; Iqbal, Munir

    2017-07-15

    H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence. IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to

  7. Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

    Science.gov (United States)

    Ty Hang, Vu Thi; Holmes, Edward C.; Veasna, Duong; Quy, Nguyen Thien; Tinh Hien, Tran; Quail, Michael; Churcher, Carol; Parkhill, Julian; Cardosa, Jane; Farrar, Jeremy; Wills, Bridget; Lennon, Niall J.; Birren, Bruce W.; Buchy, Philippe

    2010-01-01

    A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs. PMID:20651932

  8. Fitness Club

    CERN Multimedia

    Fitness Club

    2011-01-01

    The CERN Fitness Club is organising Zumba Classes on the first Wednesday of each month, starting 7 September (19.00 – 20.00). What is Zumba®? It’s an exhilarating, effective, easy-to-follow, Latin-inspired, calorie-burning dance fitness-party™ that’s moving millions of people toward joy and health. Above all it’s great fun and an excellent work out. Price: 22 CHF/person Sign-up via the following form: https://espace.cern.ch/club-fitness/Lists/Zumba%20Subscription/NewForm.aspx For more info: fitness.club@cern.ch

  9. In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine.

    Science.gov (United States)

    das Neves, José; Araújo, Francisca; Andrade, Fernanda; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2013-07-01

    Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.

  10. Fodbold Fitness

    DEFF Research Database (Denmark)

    Bennike, Søren

    Samfundet forandrer sig og ligeså gør danskernes idrætsmønstre. Fodbold Fitness, der er afhandlingens omdrejningspunkt, kan iagttages som en reaktion på disse forandringer. Afhandlingen ser nærmere på Fodbold Fitness og implementeringen af dette, der ingenlunde er nogen let opgave. Bennike bidrager...

  11. Fitness cost

    DEFF Research Database (Denmark)

    Nielsen, Karen L.; Pedersen, Thomas M.; Udekwu, Klas I.

    2012-01-01

    phage types, predominantly only penicillin resistant. We investigated whether isolates of this epidemic were associated with a fitness cost, and we employed a mathematical model to ask whether these fitness costs could have led to the observed reduction in frequency. Bacteraemia isolates of S. aureus...... from Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to phage complex 83A, clonal complex 8 based on spa type, ranging in time of isolation from 1957 to 1980 and with varyous antibiograms, including both methicillin-resistant and -susceptible isolates. The relative fitness...... of each isolate was determined in a growth competition assay with a reference isolate. Significant fitness costs of 215 were determined for the MRSA isolates studied. There was a significant negative correlation between number of antibiotic resistances and relative fitness. Multiple regression analysis...

  12. Fitness Club

    CERN Multimedia

    Fitness Club

    2012-01-01

    Open to All: http://cern.ch/club-fitness  fitness.club@cern.ch Boxing Your supervisor makes your life too tough ! You really need to release the pressure you've been building up ! Come and join the fit-boxers. We train three times a week in Bd 216, classes for beginners and advanced available. Visit our website cern.ch/Boxing General Fitness Escape from your desk with our general fitness classes, to strengthen your heart, muscles and bones, improve you stamina, balance and flexibility, achieve new goals, be more productive and experience a sense of well-being, every Monday, Wednesday and Friday lunchtime, Tuesday mornings before work and Thursday evenings after work – join us for one of our monthly fitness workshops. Nordic Walking Enjoy the great outdoors; Nordic Walking is a great way to get your whole body moving and to significantly improve the condition of your muscles, heart and lungs. It will boost your energy levels no end. Pilates A body-conditioning technique de...

  13. In vivo mutational analysis of the N-terminal region of HIV-1 Nef reveals critical motifs for the development of an AIDS-like disease in CD4C/HIV transgenic mice

    International Nuclear Information System (INIS)

    Hanna, Zaher; Priceputu, Elena; Kay, Denis G.; Poudrier, Johanne; Chrobak, Pavel; Jolicoeur, Paul

    2004-01-01

    HIV-1 Nef is a critical determinant of pathogenicity in humans and transgenic (Tg) mice. To gain a better understanding of the molecular mechanisms by which Nef induces an AIDS-like disease in Tg mice, a mutational analysis of the N-terminal domain, involved in anchoring Nef to the plasma membrane, was carried out. The pathogenic effects of these Nef mutant alleles were evaluated in Tg mice by FACS analysis and by histopathological assessment. Mutation of the myristoylation site (G2A) completely abrogated the development of the AIDS-like organ disease in Tg mice, although partial downregulation of the CD4 cell surface protein and depletion of peripheral CD4 + T-cells, but not of CD4 + CD8 + thymocytes, still occurred. Despite that, the peripheral CD4 + T cells expressing Nef G2A show normal spontaneous proliferation in vivo or after stimulation in vitro, including in an allogenic mixed leukocyte reaction (MLR). Three other internal deletion mutants of Nef, spanning amino acids 8-17 (Nef Δ8-17 ), 25-35 (Nef Δ25-35 ), and 57-66 (Nef Δ57-66 ), were also studied. Nef Δ8-17 retained full pathogenic potential, although Nef Δ25-35 and Nef Δ57-66 Tg mice were free of organ disease. However, Nef Δ25-35 Tg mice exhibited disorganization of thymic architecture and a partial depletion of peripheral CD4 + T cells. These data indicate that myristoylation and other regions at the N-terminus of Nef (aa 25-35 and 57-66) are involved in mediating severe T-cell phenotypes and organ disease, although residues 8-17 are dispensable for these Nef functions. In addition, these results indicate that at least some of the CD4 + T-cell phenotypes can develop independently of the other AIDS-like organ phenotypes. This apparent segregation of different Nef-mediated phenotypes suggests distinct mechanisms of Nef action in different populations of target cells, and may be relevant to human AIDS

  14. Identification and characterization of HIV-2 strains obtained from asymptomatic patients that do not use CCR5 or CXCR4 coreceptors

    International Nuclear Information System (INIS)

    Azevedo-Pereira, J.M.; Santos-Costa, Q.; Mansinho, K.; Moniz-Pereira, J.

    2003-01-01

    In vivo, human immunodeficiency virus type 2 (HIV-2) infection reveals several unique characteristics when compared to HIV-1 infection, the most remarkable of which is the extraordinarily long asymptomatic period. Here we describe two HIV-2 primary isolates, obtained from asymptomatic individuals, which do not infect any coreceptor-expressing cell lines tested. In those cells, we show that the absence of replication is directly related to cell entry events. Furthermore, productive infection observed in peripheral blood mononuclear cells (PBMC) was not inhibited by natural ligands and monoclonal antibodies directed to CCR5 and CXCR4. Finally, viral entry efficiency and viral progeny production of these viruses are markedly impaired in PBMC, indicating a reduced replicative fitness of both viruses. In conclusion, our data suggest that in some HIV-2 asymptomatic individuals, the circulating viruses are unable to use the major coreceptors to infect PBMC. This fact should have important implications in HIV-2 pathogenesis and transmission

  15. Fitness club

    CERN Multimedia

    Fitness club

    2013-01-01

      Nordic Walking Classes Come join the Nordic walking classes and outings offered by the CERN Fitness Club starting September 2013. Our licensed instructor Christine offers classes for people who’ve never tried Nordic Walking and who would like to learn the technique, and outings for people who have completed the classes and enjoy going out as a group. Course 1: Tuesdays 12:30 - 13:30 24 September, 1 October, 8 October, 15 October Course 2: Tuesdays 12:30 - 13:30 5 November, 12 November, 19 November, 26 November Outings will take place on Thursdays (12:30 to 13:30) from 12 September 2013. We meet at the CERN Club Barracks car park (close to Entrance A) 10 minutes before departure. Prices: 50 CHF for 4 classes, including the 10 CHF Club membership. Payments made directly to instructor. Renting Poles: Poles can be rented from Christine at 5 CHF / hour. Subscription: Please subscribe at: http://cern.ch/club-fitness Looking forward to seeing you among us! Fitness Club FitnessClub@c...

  16. Fitness Club

    CERN Multimedia

    Fitness Club

    2012-01-01

    Get in Shape for Summer with the CERN Fitness Club Saturday 23 June 2012 from 14:30 to 16.30 (doors open at 14.00) Germana’s Fitness Workshop. Build strength and stamina, sculpt and tone your body and get your heart pumping with Germana’s workout mixture of Cardio Attack, Power Pump, Power Step, Cardio Combat and Cross-Training. Where: 216 (Pump room – equipped with changing rooms and showers). What to wear: comfortable clothes and indoor sports shoes + bring a drink! How much: 15 chf Sign up here: https://espace.cern.ch/club-fitness/Lists/Test_Subscription/NewForm.aspx? Join the Party and dance yourself into shape at Marco + Marials Zumba Masterclass. Saturday 30 June 2012 from 15:00 to 16:30 Marco + Mariel’s Zumba Masterclass Where: 216 (Pump room – equipped with changing rooms and showers). What to wear: comfortable clothes and indoor sports shoes + bring a drink! How much: 25 chf Sign up here: https://espace.cern.ch/club-fitness/Lists/Zumba%20...

  17. Fitness Club

    CERN Multimedia

    Fitness Club

    2010-01-01

    Nordic Walking Please note that the subscriptions for the general fitness classes from July to December are open: Subscriptions general fitness classes Jul-Dec 2010 Sign-up to the Fitness Club mailing list here Nordic Walking: Sign-up to the Nordic Walking mailing list here Beginners Nordic walking lessons Monday Lunchtimes (rdv 12:20 for 12:30 departure) 13.09/20.09/27.09/04.10 11.10/18.10/08.11/15.11 22.11/29.11/06.12/20.12 Nordic walking lessons Tuesday evenings (rdv 17:50 for 18:00 departure) 07.09/14.09/21.09/28.09 05.10/12.10/19.10/26.10 Intermediate/Advanced Nordic walking outings (follow the nordic walking lessons before signing up for the outings) every Thursday from 16.09 - 16.12, excluding 28.10 and 09.12 Subscriptions and info: fitness.club@cern.ch  

  18. Fitness Club

    CERN Multimedia

    Fitness Club

    2012-01-01

      The CERN Fitness Club is pleased to announce its new early morning class which will be taking place on: Tuesdays from 24th April 07:30 to 08:15 216 (Pump Hall, close to entrance C) – Facilities include changing rooms and showers. The Classes: The early morning classes will focus on workouts which will help you build not only strength and stamina, but will also improve your balance, and coordination. Our qualified instructor Germana will accompany you throughout the workout  to ensure you stay motivated so you achieve the best results. Sign up and discover the best way to start your working day full of energy! How to subscribe? We invite you along to a FREE trial session, if you enjoy the activity, please sign up via our website: https://espace.cern.ch/club-fitness/Activities/SUBSCRIBE.aspx. * * * * * * * * Saturday 28th April Get in shape for the summer at our fitness workshop and zumba dance party: Fitness workshop with Germana 13:00 to 14:30 - 216 (Pump Hall) Price...

  19. Fitness Club

    CERN Multimedia

    Fitness Club

    2012-01-01

    Nordic Walking Classes Sessions of four classes of one hour each are held on Tuesdays. RDV barracks parking at Entrance A, 10 minutes before class time. Session 1 =  11.09 / 18.09 / 25.09 / 02.10, 18:15 - 19:15 Session 2 = 25.09 / 02.10 / 09.10 / 16.10, 12:30 - 13:30 Session 3 = 23.10 / 30.10 / 06.11 / 13.11, 12:30 - 13:30 Session 4 = 20.11 / 27.11 / 04.12 / 11.12, 12:30 - 13:30 Prices 40 CHF per session + 10 CHF club membership 5 CHF/hour pole rental Check out our schedule and enroll at http://cern.ch/club-fitness   Hope to see you among us!  fitness.club@cern.ch In spring 2012 there was a long-awaited progress in CERN Fitness club. We have officially opened a Powerlifting @ CERN, and the number of members of the new section has been increasing since then reaching 70+ people in less than 4 months. Powerlifting is a strength sport, which is simple as 1-2-3 and efficient. The "1-2-3" are the three basic lifts (bench press...

  20. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

  1. Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

    International Nuclear Information System (INIS)

    Muthumani, Karuppiah; Zhang Donghui; Dayes, Nathanael S.; Hwang, Daniel S.; Calarota, Sandra A.; Choo, Andrew Y.; Boyer, Jean D.; Weiner, David B.

    2003-01-01

    HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

  2. Fitness club

    CERN Multimedia

    Fitness club

    2013-01-01

    Nordic Walking Classes New session of 4 classes of 1 hour each will be held on Tuesdays in May 2013. Meet at the CERN barracks parking at Entrance A, 10 minutes before class time. Dates and time: 07.05, 14.05, 21.05 and 28.05, fom  12 h 30 to 13 h 30 Prices: 40 CHF per session + 10 CHF club membership – 5 CHF / hour pole rental Check out our schedule and enroll at http://cern.ch/club-fitness Hope to see you among us! 

  3. Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control.

    Science.gov (United States)

    Ruiz-Riol, M; Berdnik, D; Llano, A; Mothe, B; Gálvez, C; Pérez-Álvarez, S; Oriol-Tordera, B; Olvera, A; Silva-Arrieta, S; Meulbroek, M; Pujol, F; Coll, J; Martinez-Picado, J; Ganoza, C; Sanchez, J; Gómez, G; Wyss-Coray, T; Brander, C

    2017-08-15

    Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia ( P HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/β-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor ( IL27RA ) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and

  4. Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy

    NARCIS (Netherlands)

    Goudsmit, J.; Lange, J. M.; Krone, W. J.; Teunissen, M. B.; Epstein, L. G.; Danner, S. A.; van den Berg, H.; Breederveld, C.; Smit, L.; Bakker, M.

    1987-01-01

    Human immunodeficiency virus (HIV) is lymphotropic and neurotropic. In vivo clinical and immunological abnormalities develop in a large proportion of long-term HIV antibody seropositive persons. Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies,

  5. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  6. Improvements in Spectrum's fit to program data tool.

    Science.gov (United States)

    Mahiane, Severin G; Marsh, Kimberly; Grantham, Kelsey; Crichlow, Shawna; Caceres, Karen; Stover, John

    2017-04-01

    The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round. In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty. The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better. Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

  7. Inferring genetic interactions from comparative fitness data.

    Science.gov (United States)

    Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko

    2017-12-20

    Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

  8. Potential use of rapamycin in HIV infection

    DEFF Research Database (Denmark)

    Donia, Marco; McCubrey, James A; Bendtzen, Klaus

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies...... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...... replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood...

  9. The connection domain in reverse transcriptase facilitates the in vivo annealing of tRNALys3 to HIV-1 genomic RNA

    Directory of Open Access Journals (Sweden)

    Niu Meijuan

    2004-10-01

    Full Text Available Abstract The primer tRNA for reverse transcription in HIV-1, tRNALys3, is selectively packaged into the virus during its assembly, and annealed to the viral genomic RNA. The ribonucleoprotein complex that is involved in the packaging and annealing of tRNALys into HIV-1 consists of Gag, GagPol, tRNALys, lysyl-tRNA synthetase (LysRS, and viral genomic RNA. Gag targets tRNALys for viral packaging through Gag's interaction with LysRS, a tRNALys-binding protein, while reverse transcriptase (RT sequences within GagPol (the thumb domain bind to tRNALys. The further annealing of tRNALys3 to viral RNA requires nucleocapsid (NC sequences in Gag, but not the NC sequences GagPol. In this report, we further show that while the RT connection domain in GagPol is not required for tRNALys3 packaging into the virus, it is required for tRNALys3 annealing to the viral RNA genome.

  10. HIV Testing

    Science.gov (United States)

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

  11. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    Science.gov (United States)

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

  12. Hamiltonian inclusive fitness: a fitter fitness concept.

    Science.gov (United States)

    Costa, James T

    2013-01-01

    In 1963-1964 W. D. Hamilton introduced the concept of inclusive fitness, the only significant elaboration of Darwinian fitness since the nineteenth century. I discuss the origin of the modern fitness concept, providing context for Hamilton's discovery of inclusive fitness in relation to the puzzle of altruism. While fitness conceptually originates with Darwin, the term itself stems from Spencer and crystallized quantitatively in the early twentieth century. Hamiltonian inclusive fitness, with Price's reformulation, provided the solution to Darwin's 'special difficulty'-the evolution of caste polymorphism and sterility in social insects. Hamilton further explored the roles of inclusive fitness and reciprocation to tackle Darwin's other difficulty, the evolution of human altruism. The heuristically powerful inclusive fitness concept ramified over the past 50 years: the number and diversity of 'offspring ideas' that it has engendered render it a fitter fitness concept, one that Darwin would have appreciated.

  13. Efeitos da administração in vivo do ácido fitânico sobre parâmetros de homeostase redox em cerebelo de ratos jovens

    OpenAIRE

    Clarissa Günther Borges

    2015-01-01

    O ácido fitânico (Fit) é um ácido graxo saturado de cadeia ramificada que se acumula em diversas doenças peroxissomais, como na síndrome de Zellweger (SZ) e particularmente na doença de Refsum (DR). Essas doenças podem ocorrer devido a defeitos na biogênese do peroxissomo ou em alguma proteína peroxisomal envolvida na β ou α-oxidação de ácidos graxos. Os pacientes afetados geralmente apresentam disfunções neurológicas, incluindo anormalidades cerebelares. Considerando que a patogênese das alt...

  14. Potential use of rapamycin in HIV infection

    DEFF Research Database (Denmark)

    Donia, Marco; McCubrey, James A; Bendtzen, Klaus

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies......, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection....... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...

  15. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.

    Directory of Open Access Journals (Sweden)

    Katharine J Bar

    Full Text Available Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1∶20 to 1∶50 (IC(50 selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1-V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical

  16. Physical Fitness Assessment.

    Science.gov (United States)

    Valdes, Alice

    This document presents baseline data on physical fitness that provides an outline for assessing the physical fitness of students. It consists of 4 tasks and a 13-item questionnaire on fitness-related behaviors. The fitness test evaluates cardiorespiratory endurance by a steady state jog; muscular strength and endurance with a two-minute bent-knee…

  17. Unge, sundhed og fitness

    DEFF Research Database (Denmark)

    Jensen, Jens-Ole

    2003-01-01

    Artiklen redegør for udbredelsen af fitness blandt unge og diskuterer, hvor det er blevet så populært at dyrke fitness.......Artiklen redegør for udbredelsen af fitness blandt unge og diskuterer, hvor det er blevet så populært at dyrke fitness....

  18. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV: Get the Facts on HIV Testing, Prevention, and Treatment Share Tweet Linkedin Pin ... How can you lower your chance of HIV? HIV Quick Facts What is HIV? HIV is the ...

  19. Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.

    Science.gov (United States)

    Patterson, B K; Mosiman, V L; Cantarero, L; Furtado, M; Bhattacharya, M; Goolsby, C

    1998-04-01

    Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.

  20. In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.

    Science.gov (United States)

    Tsibris, Athe M N; Sagar, Manish; Gulick, Roy M; Su, Zhaohui; Hughes, Michael; Greaves, Wayne; Subramanian, Mani; Flexner, Charles; Giguel, Françoise; Leopold, Kay E; Coakley, Eoin; Kuritzkes, Daniel R

    2008-08-01

    Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

  1. Quarter Century of Anti-HIV CAR T Cells.

    Science.gov (United States)

    Wagner, Thor A

    2018-04-01

    A therapy that might cure HIV is a very important goal for the 30-40 million people living with HIV. Chimeric antigen receptor T cells have recently had remarkable success against certain leukemias, and there are reasons to believe they could be successful for HIV. This manuscript summarizes the published research on HIV CAR T cells and reviews the current anti-HIV chimeric antigen receptor strategies. Research on anti-HIV chimeric antigen receptor T cells has been going on for at least the last 25 years. First- and second-generation anti-HIV chimeric antigen receptors have been developed. First-generation anti-HIV chimeric antigen receptors were studied in clinical trials more than 15 years ago, but did not have meaningful clinical efficacy. There are some reasons to be optimistic about second-generation anti-HIV chimeric antigen receptor T cells, but they have not yet been tested in vivo.

  2. FITS: a function-fitting program

    Energy Technology Data Exchange (ETDEWEB)

    Balestrini, S.J.; Chezem, C.G.

    1982-01-01

    FITS is an iterating computer program that adjusts the parameters of a function to fit a set of data points according to the least squares criterion and then lists and plots the results. The function can be programmed or chosen from a library that is provided. The library can be expanded to include up to 99 functions. A general plotting routine, contained in the program but useful in its own right, is described separately in an Appendix.

  3. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  4. Broader tropism and higher cytopathicity for CD4+ T cells of a syncytium-inducing compared to a non-syncytium-inducing HIV-1 isolate as a mechanism for accelerated CD4+ T cell decline in vivo

    NARCIS (Netherlands)

    Fouchier, R. A.; Meyaard, L.; Brouwer, M.; Hovenkamp, E.; Schuitemaker, H.

    1996-01-01

    The emergence of syncytium-inducing (SI) HIV-1 isolates in infected individuals precedes an accelerated CD4+ T cell decline and is associated with high virus load and rapid disease progression. The exact mechanism by which SI HIV-1 variants may cause this enhanced clinical progression is unknown.

  5. Computer code FIT

    International Nuclear Information System (INIS)

    Rohmann, D.; Koehler, T.

    1987-02-01

    This is a description of the computer code FIT, written in FORTRAN-77 for a PDP 11/34. FIT is an interactive program to decude position, width and intensity of lines of X-ray spectra (max. length of 4K channels). The lines (max. 30 lines per fit) may have Gauss- or Voigt-profile, as well as exponential tails. Spectrum and fit can be displayed on a Tektronix terminal. (orig.) [de

  6. Aerobic endurance in HIV-positive young adults and HIV-negative ...

    African Journals Online (AJOL)

    Background: Aerobic endurance is an important aspect of physical fitness that enables individuals living with HIV to endure in the work place as well as in agricultural operations in order to earn a living and improve their quality of life. However, despite high HIV prevalence rates, the aerobic endurance status of young ...

  7. Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

    Science.gov (United States)

    Schmechel, S C; Russell, N; Hladik, F; Lang, J; Wilson, A; Ha, R; Desbien, A; McElrath, M J

    2001-11-01

    Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

  8. FITS: a function-fitting program

    Energy Technology Data Exchange (ETDEWEB)

    Balestrini, S.J.; Chezem, C.G.

    1982-08-01

    FITS is an iterating computer program that adjusts the parameters of a function to fit a set of data points according to the least squares criterion and then lists and plots the results. The function can be programmed or chosen from a library that is provided. The library can be expanded to include up to 99 functions. A general plotting routine, contained in the program but useful in its own right, is described separately in Appendix A. An example problem file and its solution is given in Appendix B.

  9. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    Administrator

    2007-05-16

    May 16, 2007 ... Other issues of safety are dependant upon choice of enzyme gene deli- very, and although various ex vivo and in vivo gene transfer techniques exist, we believe that a recom-binant. HIV viral vector whose pathogenesis gene, NEF has been removed to render it impotent, could offer a more targeted delivery ...

  10. Getting CSR communication fit

    DEFF Research Database (Denmark)

    Schmeltz, Line

    2017-01-01

    Companies experience increasing legal and societal pressure to communicate about their corporate social responsibility (CSR) engagements from a number of different publics. One very important group is that of young consumers who are predicted to be the most important and influential consumer group...... in the near future. From a value- theoretical base, this article empirically explores the role and applicability of ‘fit’ in strategic CSR communication targeted at young consumers. Point of departure is taken in the well-known strategic fit (a logical link between a company’s CSR commitment and its core...... values) and is further developed by introducing two additional fits, the CSR- Consumer fit and the CSR-Consumer-Company fit (Triple Fit). Through a sequential design, the three fits are empirically tested and their potential for meeting young consumers’ expectations for corporate CSR messaging...

  11. Fragment Impact Toolkit (FIT)

    Energy Technology Data Exchange (ETDEWEB)

    Shevitz, Daniel Wolf [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Key, Brian P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Garcia, Daniel B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-05

    The Fragment Impact Toolkit (FIT) is a software package used for probabilistic consequence evaluation of fragmenting sources. The typical use case for FIT is to simulate an exploding shell and evaluate the consequence on nearby objects. FIT is written in the programming language Python and is designed as a collection of interacting software modules. Each module has a function that interacts with the other modules to produce desired results.

  12. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

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

  13. Identifying HIV-1 dual infections

    Directory of Open Access Journals (Sweden)

    Cornelissen Marion

    2007-09-01

    Full Text Available Abstract Transmission of human immunodeficiency virus (HIV is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus and superinfections (second infection after a specific immune response to the first infecting strain has developed can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR strains could recombine to produce a pan-resistant, transmittable virus. We will describe in this review what is presently known about super- and re-infection among ambient viral infections, as well as the first cases of HIV-1 superinfection, including HIV-1 triple infections. The clinical implications, the impact of the immune system, and the effect of anti-retroviral therapy will be covered, as will as the timing of HIV superinfection. The methods used to detect HIV-1 dual infections will be discussed in detail. To increase the likelihood of detecting a dual HIV-1 infection, pre-selection of patients can be done by serotyping, heteroduplex mobility assays (HMA, counting the degenerate base codes in the HIV-1 genotyping sequence, or surveying unexpected increases in the

  14. Fitness: Tips for Staying Motivated

    Science.gov (United States)

    Healthy Lifestyle Fitness Fitness is for life. Motivate yourself with these practical tips. By Mayo Clinic Staff Have ... 27, 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/fitness/art-20047624 . Mayo Clinic ...

  15. Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection

    International Nuclear Information System (INIS)

    Liu Yi; Mullins, James I.; Mittler, John E.

    2006-01-01

    The failure of HIV-1 to escape at some cytotoxic T-lymphocyte (CTL) epitopes has generally been explained in terms of viral fitness costs or ineffective or attenuated CTL responses. Relatively little attention has been paid to the evolutionary time required for escape mutants to be detected. This time is significantly affected by selection, mutation rates, the presence of other advantageous mutations, and the effective population size of HIV-1 in vivo (typically estimated to be ∼10 3 in chronically infected patients, though one study has estimated it to be ∼10 5 ). Here, we use a forward simulator with experimentally estimated HIV-1 parameters to show that these delays can be substantial. For an effective population size of 10 3 , even highly advantageous mutants (s = 0.5) may not be detected for a couple of years in chronically infected patients, while moderately advantageous escape mutants (s = 0.1) may not be detected for up to 10 years. Even with an effective population size of 10 5 , a moderately advantageous escape mutant (s = 0.1) may not be detected in the population within 2 years if it has to compete with other selectively advantageous mutants. Stochastic evolutionary forces, therefore, in addition to viral fitness costs and ineffective or attenuated CTL responses, must be taken into account when assessing the selection of CTL escape mutations

  16. Limitations of inclusive fitness.

    Science.gov (United States)

    Allen, Benjamin; Nowak, Martin A; Wilson, Edward O

    2013-12-10

    Until recently, inclusive fitness has been widely accepted as a general method to explain the evolution of social behavior. Affirming and expanding earlier criticism, we demonstrate that inclusive fitness is instead a limited concept, which exists only for a small subset of evolutionary processes. Inclusive fitness assumes that personal fitness is the sum of additive components caused by individual actions. This assumption does not hold for the majority of evolutionary processes or scenarios. To sidestep this limitation, inclusive fitness theorists have proposed a method using linear regression. On the basis of this method, it is claimed that inclusive fitness theory (i) predicts the direction of allele frequency changes, (ii) reveals the reasons for these changes, (iii) is as general as natural selection, and (iv) provides a universal design principle for evolution. In this paper we evaluate these claims, and show that all of them are unfounded. If the objective is to analyze whether mutations that modify social behavior are favored or opposed by natural selection, then no aspect of inclusive fitness theory is needed.

  17. GOSSIP: SED fitting code

    Science.gov (United States)

    Franzetti, Paolo; Scodeggio, Marco

    2012-10-01

    GOSSIP fits the electro-magnetic emission of an object (the SED, Spectral Energy Distribution) against synthetic models to find the simulated one that best reproduces the observed data. It builds-up the observed SED of an object (or a large sample of objects) combining magnitudes in different bands and eventually a spectrum; then it performs a chi-square minimization fitting procedure versus a set of synthetic models. The fitting results are used to estimate a number of physical parameters like the Star Formation History, absolute magnitudes, stellar mass and their Probability Distribution Functions.

  18. Fitness Club / Nordic Walking

    CERN Multimedia

    Fitness Club

    2011-01-01

    Nordic Walking at CERN Enrollments are open for Nordic Walking courses and outings at CERN. Classes will be on Tuesdays as of 20 September, and outings for the more experienced will be on Thursdays as of 15 September. We meet at the CERN Club barracks car park (near entrance A). • 18:00 to 19:00 on 20 & 27 September, as well as 4 & 11 October. Check out our schedule and rates and enroll at: http://cern.ch/club-fitness Hope to see you among us! CERN Fitness Club fitness.club@cern.ch  

  19. Tools for Visualizing HIV in Cure Research.

    Science.gov (United States)

    Niessl, Julia; Baxter, Amy E; Kaufmann, Daniel E

    2018-02-01

    The long-lived HIV reservoir remains a major obstacle for an HIV cure. Current techniques to analyze this reservoir are generally population-based. We highlight recent developments in methods visualizing HIV, which offer a different, complementary view, and provide indispensable information for cure strategy development. Recent advances in fluorescence in situ hybridization techniques enabled key developments in reservoir visualization. Flow cytometric detection of HIV mRNAs, concurrently with proteins, provides a high-throughput approach to study the reservoir on a single-cell level. On a tissue level, key spatial information can be obtained detecting viral RNA and DNA in situ by fluorescence microscopy. At total-body level, advancements in non-invasive immuno-positron emission tomography (PET) detection of HIV proteins may allow an encompassing view of HIV reservoir sites. HIV imaging approaches provide important, complementary information regarding the size, phenotype, and localization of the HIV reservoir. Visualizing the reservoir may contribute to the design, assessment, and monitoring of HIV cure strategies in vitro and in vivo.

  20. Sexual behavior and risk practices of HIV positive and HIV negative Rwandan women

    Science.gov (United States)

    ADEDIMEJI, Adebola A.; HOOVER, Donald R.; SHI, Qiuhu; GARD, Tracy; MUTIMURA, Eugene; SINAYOBYE, Jean d’Amour; COHEN, Mardge H.; ANASTOS, Kathryn

    2014-01-01

    It is not well understood how infection with HIV and prior experience of sexual violence affects sexual behavior in African women. We describe factors influencing current sexual practices of Rwandan women living with or without HIV/AIDS. By design, 75% of participants were HIV positive and ~50% reported having experienced genocidal rape. Univariate and multivariate logistic regression models were fit to describe demographic and clinical characteristics that influenced sexual behavior in the previous 6 months, condom use, history of transactional sex, and prior infection with a non-HIV sexually transmitted disease. Respondents’ age, where they lived, whether or not they lived with a husband or partner, experience of sexual trauma, CD4 count, CES-D and PTSD scores were strongly associated with risky sexual behavior and infection with non-HIV STI. HIV positive women with a history of sexual violence in the contexts of war and conflict may be susceptible to some high-risk sexual behaviors. PMID:25488169

  1. Measuring Your Fitness Level

    Science.gov (United States)

    ... online calculator. If you'd rather do the math yourself, divide your weight in pounds by your ... Human Services recommends one of the following activity levels for adult fitness and health benefits: 150 minutes ...

  2. The universal Higgs fit

    DEFF Research Database (Denmark)

    Giardino, P. P.; Kannike, K.; Masina, I.

    2014-01-01

    We perform a state-of-the-art global fit to all Higgs data. We synthesise them into a 'universal' form, which allows to easily test any desired model. We apply the proposed methodology to extract from data the Higgs branching ratios, production cross sections, couplings and to analyse composite...... Higgs models, models with extra Higgs doublets, supersymmetry, extra particles in the loops, anomalous top couplings, and invisible Higgs decays into Dark Matter. Best fit regions lie around the Standard Model predictions and are well approximated by our 'universal' fit. Latest data exclude the dilaton...... as an alternative to the Higgs, and disfavour fits with negative Yukawa couplings. We derive for the first time the SM Higgs boson mass from the measured rates, rather than from the peak positions, obtaining M-h = 124.4 +/- 1.6 GeV....

  3. ACSM Fit Society Page

    Science.gov (United States)

    ... fitness topics. Expert commentary and features on exercise, nutrition, sports and health offer tips and techniques for maintaining ... Special Populations 2011 -- Behavior Change & Exercise Adherence 2011 -- ... Preparing for Fall Sports 2009 -- Cancer and Exercise 2008 -- Group Exercise 2008 -- ...

  4. Driver fitness medical guidelines.

    Science.gov (United States)

    2009-09-01

    This guide provides guidance to assist licensing agencies in making decisions about an individuals fitness for driving. This is the first attempt to produce a consolidated document covering medical conditions included in the task agreement between...

  5. Choice in HIV testing: the acceptability and anticipated use of a self ...

    African Journals Online (AJOL)

    Combination HIV prevention is being widely promoted by funders. This strategy aims to offer HIV prevention choices that can be selected and combined to decrease HIV risk in ways that fit with each individual's situation. Treatment as prevention and pre-exposure prophylaxis are two new evidence-based strategies to ...

  6. The Langley Fitness Center

    Science.gov (United States)

    1993-01-01

    NASA Langley recognizes the importance of healthy employees by committing itself to offering a complete fitness program. The scope of the program focuses on promoting overall health and wellness in an effort to reduce the risks of illness and disease and to increase productivity. This is accomplished through a comprehensive Health and Fitness Program offered to all NASA employees. Various aspects of the program are discussed.

  7. dftools: Distribution function fitting

    Science.gov (United States)

    Obreschkow, Danail

    2018-05-01

    dftools, written in R, finds the most likely P parameters of a D-dimensional distribution function (DF) generating N objects, where each object is specified by D observables with measurement uncertainties. For instance, if the objects are galaxies, it can fit a mass function (D=1), a mass-size distribution (D=2) or the mass-spin-morphology distribution (D=3). Unlike most common fitting approaches, this method accurately accounts for measurement in uncertainties and complex selection functions.

  8. HIV/AIDS Related Knowledge and Perceived Risk Associated with ...

    African Journals Online (AJOL)

    Using data from the 2004 National Survey of Adolescents in Uganda, logistic regression models were fitted to examine the odds that HIV/AIDS related knowledge and perceived risk of HIV infection are associated with condom use among adolescents. After including demographic measures, findings indicated that correct ...

  9. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  10. HIV/AIDS

    Science.gov (United States)

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

  11. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  12. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: January 17, 2018 Key ...

  13. HIV and AIDS

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  14. HIV Treatment: The Basics

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Treatment: The Basics Last Reviewed: March 22, 2018 ...

  15. HIV and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV ... HIV and Pregnancy FAQ113, July 2017 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus ( ...

  16. HIV and Cardiovascular Disease

    Science.gov (United States)

    ... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

  17. Rules, culture, and fitness.

    Science.gov (United States)

    Baum, W M

    1995-01-01

    Behavior analysis risks intellectual isolation unless it integrates its explanations with evolutionary theory. Rule-governed behavior is an example of a topic that requires an evolutionary perspective for a full understanding. A rule may be defined as a verbal discriminative stimulus produced by the behavior of a speaker under the stimulus control of a long-term contingency between the behavior and fitness. As a discriminative stimulus, the rule strengthens listener behavior that is reinforced in the short run by socially mediated contingencies, but which also enters into the long-term contingency that enhances the listener's fitness. The long-term contingency constitutes the global context for the speaker's giving the rule. When a rule is said to be "internalized," the listener's behavior has switched from short- to long-term control. The fitness-enhancing consequences of long-term contingencies are health, resources, relationships, or reproduction. This view ties rules both to evolutionary theory and to culture. Stating a rule is a cultural practice. The practice strengthens, with short-term reinforcement, behavior that usually enhances fitness in the long run. The practice evolves because of its effect on fitness. The standard definition of a rule as a verbal statement that points to a contingency fails to distinguish between a rule and a bargain ("If you'll do X, then I'll do Y"), which signifies only a single short-term contingency that provides mutual reinforcement for speaker and listener. In contrast, the giving and following of a rule ("Dress warmly; it's cold outside") can be understood only by reference also to a contingency providing long-term enhancement of the listener's fitness or the fitness of the listener's genes. Such a perspective may change the way both behavior analysts and evolutionary biologists think about rule-governed behavior.

  18. HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  19. Basic HIV/AIDS Statistics

    Science.gov (United States)

    ... HIV Syndicated Content Website Feedback HIV/AIDS Basic Statistics Recommend on Facebook Tweet Share Compartir HIV and ... HIV. Interested in learning more about CDC's HIV statistics? Terms, Definitions, and Calculations Used in CDC HIV ...

  20. Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research

    DEFF Research Database (Denmark)

    Denton, Paul W.; Søgaard, Ole Schmeltz; Tolstrup, Martin

    2016-01-01

    Research challenges associated with understanding HIV persistence during antiretroviral therapy can be categorized as temporal, spatial and combinatorial. Temporal research challenges relate to the timing of events during establishment and maintenance of HIV persistence. Spatial research challeng...... for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence....... will improve our understanding of HIV persistence and move the field closer to achieving eradication of persistent HIV. Given that humanized mice and non-human primate HIV models permit rigorous control of experimental conditions, these models have been used extensively as in vivo research platforms...

  1. Living with HIV

    Science.gov (United States)

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

  2. HIV Risk and Prevention

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Risk and Prevention Recommend on Facebook Tweet Share ...

  3. Fitting the Phenomenological MSSM

    CERN Document Server

    AbdusSalam, S S; Quevedo, F; Feroz, F; Hobson, M

    2010-01-01

    We perform a global Bayesian fit of the phenomenological minimal supersymmetric standard model (pMSSM) to current indirect collider and dark matter data. The pMSSM contains the most relevant 25 weak-scale MSSM parameters, which are simultaneously fit using `nested sampling' Monte Carlo techniques in more than 15 years of CPU time. We calculate the Bayesian evidence for the pMSSM and constrain its parameters and observables in the context of two widely different, but reasonable, priors to determine which inferences are robust. We make inferences about sparticle masses, the sign of the $\\mu$ parameter, the amount of fine tuning, dark matter properties and the prospects for direct dark matter detection without assuming a restrictive high-scale supersymmetry breaking model. We find the inferred lightest CP-even Higgs boson mass as an example of an approximately prior independent observable. This analysis constitutes the first statistically convergent pMSSM global fit to all current data.

  4. Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

    Science.gov (United States)

    Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

    2010-11-01

    To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

  5. Strength Training: For Overall Fitness

    Science.gov (United States)

    Healthy Lifestyle Fitness Strength training is an important part of an overall fitness program. Here's what strength training can do for ... is a key component of overall health and fitness for everyone. Lean muscle mass naturally diminishes with ...

  6. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

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

  7. Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

    Science.gov (United States)

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Goujard, Cécile; Deveau, Christiane; Meyer, Laurence; Ngo, Nicole; Rouzioux, Christine; Guillet, Jean-Gérard; Delfraissy, Jean-François; Sinet, Martine; Venet, Alain

    1999-01-01

    HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination. J. Clin. Invest. 104:1431–1439 (1999). PMID:10562305

  8. Improving NEC Fit

    Science.gov (United States)

    2015-09-01

    TAD Temporary Additional Duty TFMMS Total Force Manpower Management System UIC Unit Identification Code USFFC United States Fleet Forces Command...not include sailors on temporary additional duty ( TAD ). In addition, for class average Fit, we excluded units that had billets but no onboard

  9. Reliability and Model Fit

    Science.gov (United States)

    Stanley, Leanne M.; Edwards, Michael C.

    2016-01-01

    The purpose of this article is to highlight the distinction between the reliability of test scores and the fit of psychometric measurement models, reminding readers why it is important to consider both when evaluating whether test scores are valid for a proposed interpretation and/or use. It is often the case that an investigator judges both the…

  10. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors.

    Directory of Open Access Journals (Sweden)

    Christina Gavegnano

    2017-12-01

    Full Text Available Despite advances in the treatment of HIV infection with ART, elucidating strategies to overcome HIV persistence, including blockade of viral reservoir establishment, maintenance, and expansion, remains a challenge. T cell homeostasis is a major driver of HIV persistence. Cytokines involved in regulating homeostasis of memory T cells, the major hub of the HIV reservoir, trigger the Jak-STAT pathway. We evaluated the ability of tofacitinib and ruxolitinib, two FDA-approved Jak inhibitors, to block seeding and maintenance of the HIV reservoir in vitro. We provide direct demonstration for involvement of the Jak-STAT pathway in HIV persistence in vivo, ex vivo, and in vitro; pSTAT5 strongly correlates with increased levels of integrated viral DNA in vivo, and in vitro Jak inhibitors reduce the frequency of CD4+ T cells harboring integrated HIV DNA. We show that Jak inhibitors block viral production from infected cells, inhibit γ-C receptor cytokine (IL-15-induced viral reactivation from latent stores thereby preventing transmission of infectious particles to bystander activated T cells. These results show that dysregulation of the Jak-STAT pathway is associated with viral persistence in vivo, and that Jak inhibitors target key events downstream of γ-C cytokine (IL-2, IL-7 and IL-15 ligation to their receptors, impacting the magnitude of the HIV reservoir in all memory CD4 T cell subsets in vitro and ex vivo. Jak inhibitors represent a therapeutic modality to prevent key events of T cell activation that regulate HIV persistence and together, specific, potent blockade of these events may be integrated to future curative strategies.

  12. Fitting PAC spectra with stochastic models: PolyPacFit

    Energy Technology Data Exchange (ETDEWEB)

    Zacate, M. O., E-mail: zacatem1@nku.edu [Northern Kentucky University, Department of Physics and Geology (United States); Evenson, W. E. [Utah Valley University, College of Science and Health (United States); Newhouse, R.; Collins, G. S. [Washington State University, Department of Physics and Astronomy (United States)

    2010-04-15

    PolyPacFit is an advanced fitting program for time-differential perturbed angular correlation (PAC) spectroscopy. It incorporates stochastic models and provides robust options for customization of fits. Notable features of the program include platform independence and support for (1) fits to stochastic models of hyperfine interactions, (2) user-defined constraints among model parameters, (3) fits to multiple spectra simultaneously, and (4) any spin nuclear probe.

  13. HIV, violence, blame and shame: pathways of risk to internalized HIV stigma among South African adolescents living with HIV.

    Science.gov (United States)

    Pantelic, Marija; Boyes, Mark; Cluver, Lucie; Meinck, Franziska

    2017-08-21

    Internalized HIV stigma is a key risk factor for negative outcomes amongst adolescents living with HIV (ALHIV), including non-adherence to anti-retroviral treatment, loss-to-follow-up and morbidity. This study tested a theoretical model of multi-level risk pathways to internalized HIV stigma among South African ALHIV. From 2013 to 2015, a survey using t otal population sampling of ALHIV who had ever initiated anti-retroviral treatment (ART) in 53 public health facilities in the Eastern Cape, South Africa was conducted. Community-tracing ensured inclusion of ALHIV who were defaulting from ART or lost to follow-up. 90.1% of eligible ALHIV were interviewed ( n  = 1060, 55% female, mean age = 13.8, 21% living in rural locations). HIV stigma mechanisms (internalized, enacted, and anticipated), HIV-related disability, violence victimization (physical, emotional, sexual abuse, bullying victimization) were assessed using well-validated self-report measures. Structural equation modelling was used to test a theoretically informed model of risk pathways from HIV-related disability to internalized HIV stigma. The model controlled for age, gender and urban/rural address. Prevalence of internalized HIV stigma was 26.5%. As hypothesized, significant associations between internalized stigma and anticipated stigma, as well as depression were obtained. Unexpectedly, HIV-related disability, victimization, and enacted stigma were not directly associated with internalized stigma. Instead significant pathways were identified via anticipated HIV stigma and depression. The model fitted the data well (RMSEA = .023; CFI = .94; TLI = .95; WRMR = 1.070). These findings highlight the complicated nature of internalized HIV stigma. Whilst it is seemingly a psychological process, indirect pathways suggest multi-level mechanisms leading to internalized HIV stigma. Findings suggest that protection from violence within homes, communities and schools may interrupt risk pathways from HIV

  14. Extensive fitness and human cooperation

    NARCIS (Netherlands)

    van Hateren, J. H.

    2015-01-01

    Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to increase their fitness. The combined effect is known

  15. Fit-for-Purpose

    DEFF Research Database (Denmark)

    Enemark, Stig

    2013-01-01

    ; completeness to cover the total jurisdiction; and credibility in terms of reliable data being trusted by the users. Accuracy can then be incrementally improved over time when relevant and justified by serving the needs of citizen, business and society in general. Such a fit-for-purpose approach is fundamental...... systems act within adopted land policies that define the legal regulatory pattern for dealing with land issues. Land administration systems - whether highly advanced or very basic – require a spatial framework to operate. This framework provides the fundamental information for dealing with land issues...... concepts may well be seen as the end target but not as the point of entry. When assessing the technology and investment choices the focus should be on building a fit-for-purpose framework that will meet the needs of society today and that can be incrementally improved over time....

  16. Convolution based profile fitting

    International Nuclear Information System (INIS)

    Kern, A.; Coelho, A.A.; Cheary, R.W.

    2002-01-01

    Full text: In convolution based profile fitting, profiles are generated by convoluting functions together to form the observed profile shape. For a convolution of 'n' functions this process can be written as, Y(2θ)=F 1 (2θ)x F 2 (2θ)x... x F i (2θ)x....xF n (2θ). In powder diffractometry the functions F i (2θ) can be interpreted as the aberration functions of the diffractometer, but in general any combination of appropriate functions for F i (2θ) may be used in this context. Most direct convolution fitting methods are restricted to combinations of F i (2θ) that can be convoluted analytically (e.g. GSAS) such as Lorentzians, Gaussians, the hat (impulse) function and the exponential function. However, software such as TOPAS is now available that can accurately convolute and refine a wide variety of profile shapes numerically, including user defined profiles, without the need to convolute analytically. Some of the most important advantages of modern convolution based profile fitting are: 1) virtually any peak shape and angle dependence can normally be described using minimal profile parameters in laboratory and synchrotron X-ray data as well as in CW and TOF neutron data. This is possible because numerical convolution and numerical differentiation is used within the refinement procedure so that a wide range of functions can easily be incorporated into the convolution equation; 2) it can use physically based diffractometer models by convoluting the instrument aberration functions. This can be done for most laboratory based X-ray powder diffractometer configurations including conventional divergent beam instruments, parallel beam instruments, and diffractometers used for asymmetric diffraction. It can also accommodate various optical elements (e.g. multilayers and monochromators) and detector systems (e.g. point and position sensitive detectors) and has already been applied to neutron powder diffraction systems (e.g. ANSTO) as well as synchrotron based

  17. MixFit

    DEFF Research Database (Denmark)

    Haller, Toomas; Leitsalu, Liis; Fischer, Krista

    2017-01-01

    Ancestry information at the individual level can be a valuable resource for personalized medicine, medical, demographical and history research, as well as for tracing back personal history. We report a new method for quantitatively determining personal genetic ancestry based on genome-wide data....... Numerical ancestry component scores are assigned to individuals based on comparisons with reference populations. These comparisons are conducted with an existing analytical pipeline making use of genotype phasing, similarity matrix computation and our addition-multidimensional best fitting by Mix......Fit. The method is demonstrated by studying Estonian and Finnish populations in geographical context. We show the main differences in the genetic composition of these otherwise close European populations and how they have influenced each other. The components of our analytical pipeline are freely available...

  18. Intensity Conserving Spectral Fitting

    Science.gov (United States)

    Klimchuk, J. A.; Patsourakos, S.; Tripathi, D.

    2015-01-01

    The detailed shapes of spectral line profiles provide valuable information about the emitting plasma, especially when the plasma contains an unresolved mixture of velocities, temperatures, and densities. As a result of finite spectral resolution, the intensity measured by a spectrometer is the average intensity across a wavelength bin of non-zero size. It is assigned to the wavelength position at the center of the bin. However, the actual intensity at that discrete position will be different if the profile is curved, as it invariably is. Standard fitting routines (spline, Gaussian, etc.) do not account for this difference, and this can result in significant errors when making sensitive measurements. Detection of asymmetries in solar coronal emission lines is one example. Removal of line blends is another. We have developed an iterative procedure that corrects for this effect. It can be used with any fitting function, but we employ a cubic spline in a new analysis routine called Intensity Conserving Spline Interpolation (ICSI). As the name implies, it conserves the observed intensity within each wavelength bin, which ordinary fits do not. Given the rapid convergence, speed of computation, and ease of use, we suggest that ICSI be made a standard component of the processing pipeline for spectroscopic data.

  19. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells.

    Science.gov (United States)

    Oufir, Mouhssin; Bisset, Leslie R; Hoffmann, Stefan R K; Xue, Gongda; Klauser, Stephan; Bergamaschi, Bianca; Gervaix, Alain; Böni, Jürg; Schüpbach, Jörg; Gutte, Bernd

    2011-01-01

    An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  20. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

    Directory of Open Access Journals (Sweden)

    Mouhssin Oufir

    2011-01-01

    Full Text Available An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  1. HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

    Science.gov (United States)

    Sengayi, Mazvita; Babb, Chantal; Egger, Matthias; Urban, Margaret I

    2015-03-18

    HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children associated with previous HIV testing. In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

  2. Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies

    Science.gov (United States)

    Louie, Raymond H. Y.; Kaczorowski, Kevin J.; Chakraborty, Arup K.; McKay, Matthew R.

    2018-01-01

    HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge is the design of immunogens and vaccination protocols that can elicit bnAbs that target regions of the virus’s spike proteins where the likelihood of mutational escape is low due to the high fitness cost of mutations. Related challenges include the choice of combinations of bnAbs for therapy. An accurate representation of viral fitness as a function of its protein sequences (a fitness landscape), with explicit accounting of the effects of coupling between mutations, could help address these challenges. We describe a computational approach that has allowed us to infer a fitness landscape for gp160, the HIV polyprotein that comprises the viral spike that is targeted by antibodies. We validate the inferred landscape through comparisons with experimental fitness measurements, and various other metrics. We show that an effective antibody that prevents immune escape must selectively bind to high escape cost residues that are surrounded by those where mutations incur a low fitness cost, motivating future applications of our landscape for immunogen design. PMID:29311326

  3. Get Tested for HIV

    Science.gov (United States)

    ... AIDS: What is HIV/AIDS? Women and HIV/AIDS Next section ... Tested? Why do I need to get tested for HIV? The only way to know if you have HIV is to get tested. Many people with HIV don’t have any symptoms. In the United States, about 1 in 7 ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, ...

  5. Asymptomatic HIV infection

    Science.gov (United States)

    ... of HIV/AIDS during which there are no symptoms of HIV infection. During this phase, the immune system in someone with HIV slowly weakens, but the person has no symptoms. How long this phase lasts depends on how ...

  6. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

  7. Dance your way to fitness

    Science.gov (United States)

    ... ency/patientinstructions/000809.htm Dance your way to fitness To use the sharing features on this page, ... to rhythm and music. Many health clubs and fitness centers offer dance workout classes, such as Zumba. ...

  8. Competency profile of Fitness Instructor

    OpenAIRE

    Peterová, Marta

    2011-01-01

    Title: COMPETENCY PROFILE OF FITNESS INSTRUCTOR Objectives: The aim of this work is to find out competencies of fitness instructor and make a competency profile, containing competencies, which are important for excellent fitness instructor. Methods: I applied the method of interview and the method of research in my thesis. The interview was used to make a list of competencies of fitness instructor. The research was applied in the final part of making competency profile, for an attestation of ...

  9. Methodology review: evaluating person fit

    NARCIS (Netherlands)

    Meijer, R.R.; Sijtsma, Klaas

    2001-01-01

    Person-fit methods based on classical test theory-and item response theory (IRT), and methods investigating particular types of response behavior on tests, are examined. Similarities and differences among person-fit methods and their advantages and disadvantages are discussed. Sound person-fit

  10. EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

    Science.gov (United States)

    Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

    2018-06-01

    Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

  11. Fitness for duty

    International Nuclear Information System (INIS)

    Barnes, D.; Matney, C.

    1991-01-01

    A Fitness For Duty training program was developed to satisfy the requirements of the NRC, 10 CFR 26, 10 CFR 707 and to meet requirements at the Westinghouse Savannah River Company. Interactive videodisc technology was selected as the training medium using the TenCore authoring language. Computer-based training was chosen because of the large number of trainees, the advantages of the reduced overall cost, and the increased trainee retention of course material compared to traditional instruction. The resulting training program utilizes extensive role playing exercises in which employees and supervisors are exposed to real life situations. Extensive interactions by the trainees are required in that they must answer questions concerning the behav ior of individuals, random and for-cause drug testing, and the employee assistance program. Feedback is given in each case. Emphasis is placed on recognition of deteriorating job performance

  12. Multivariate rational data fitting

    Science.gov (United States)

    Cuyt, Annie; Verdonk, Brigitte

    1992-12-01

    Sections 1 and 2 discuss the advantages of an object-oriented implementation combined with higher floating-point arithmetic, of the algorithms available for multivariate data fitting using rational functions. Section 1 will in particular explain what we mean by "higher arithmetic". Section 2 will concentrate on the concepts of "object orientation". In sections 3 and 4 we shall describe the generality of the data structure that can be dealt with: due to some new results virtually every data set is acceptable right now, with possible coalescence of coordinates or points. In order to solve the multivariate rational interpolation problem the data sets are fed to different algorithms depending on the structure of the interpolation points in then-variate space.

  13. Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

    Science.gov (United States)

    Gringeri, A; Santagostino, E; Muça-Perja, M; Mannucci, P M; Zagury, J F; Bizzini, B; Lachgar, A; Carcagno, M; Rappaport, J; Criscuolo, M; Blattner, W; Burny, A; Gallo, R C; Zagury, D

    1998-01-01

    To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

  14. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  15. Sensitization of Parker fittings

    International Nuclear Information System (INIS)

    Wilber, W.W.

    1985-09-01

    At your request, ferrules from 316 SS Parker-Hannifen compression fittings at the FFTF have been examined and evaluated to determine the metallurgical condition as related to carbide precipitation in grain boundaries (known as sensitization) and the implications this may have with regard to corrosion resistance. To accomplish this, two ferrules from new stock, two ferrules from old stock and two ferrules that had seen service were examined metallurgically. The samples were prepared for optical metallography. They were viewed in both the etched and unetched condition and analyzed on the scanning electron microscope (SEM) for elemental content. It was confirmed that the ferrules from new stock had a 5 mil thick nitrided layer on the ferrule ID at the lead end and that the 316 SS ferrule material was in the sensitized condition, indicating low resistance to aqueous corrosion. The material from old stock had no nitride layer but was in the sensitized condition indicating low resistance to aqueous corrosion. The ferrules that had seen service had not been nitrided and were not sensitized indicating high resistance to aqueous corrosion

  16. Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

    Directory of Open Access Journals (Sweden)

    Sekar Natesampillai

    2010-11-01

    Full Text Available In medicine, understanding the pathophysiologic basis of exceptional circumstances has led to an enhanced understanding of biology. We have studied the circumstance of HIV-infected patients in whom antiretroviral therapy results in immunologic benefit, despite virologic failure. In such patients, two protease mutations, I54V and V82A, occur more frequently. Expressing HIV protease containing these mutations resulted in less cell death, caspase activation, and nuclear fragmentation than wild type (WT HIV protease or HIV protease containing other mutations. The impaired induction of cell death was also associated with impaired cleavage of procaspase 8, a requisite event for HIV protease mediated cell death. Primary CD4 T cells expressing I54V or V82A protease underwent less cell death than with WT or other mutant proteases. Human T cells infected with HIV containing these mutations underwent less cell death and less Casp8p41 production than WT or HIV containing other protease mutations, despite similar degrees of viral replication. The reductions in cell death occurred both within infected cells, as well as in uninfected bystander cells. These data indicate that single point mutations within HIV protease which are selected in vivo can significantly impact the ability of HIV to kill CD4 T cells, while not impacting viral replication. Therefore, HIV protease regulates both HIV replication as well as HIV induced T cell depletion, the hallmark of HIV pathogenesis.

  17. HIV Structural Database

    Science.gov (United States)

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

  18. HIV Viral Load

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  19. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

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

  20. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

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

  1. Epidemia de fitness

    Directory of Open Access Journals (Sweden)

    Wanja Bastos

    2013-06-01

    Full Text Available Este artigo tem como objetivo refletir sobre uma condição naturalizada e disseminada principalmente pelo campo da nova promoção à saúde e reforçada nos espaços de atuação da educação física, a que se denominou epidemia de fitness. O termo refere-se a hábitos e comportamentos obsessivos com a saúde, beleza e vitalidade, tornando-se alvo de exercício de controle por parte de especialistas. Para discuti-la realizou-se um estudo de caso em que foram submetidos à análise semiótica, por meio do método de leitura isotópica, 59 materiais de divulgação, impressos, coletados na Expo Wellness Rio 2009, uma feira de negócios inserida no Congresso Wellness Rio 2009. As categorias isotópicas que emergiram a partir da análise são as seguintes: saúde/beleza e tecnologia, saúde/beleza e especialidade e saúde/beleza e longevidade. Elas apontam para a potencialização da vitalidade humana como mola propulsora das estratégias discursivas, assim como valor recorrente que embasa ações voltadas para a melhoria das condições de saúde, imbricadas à ideia de longevidade e beleza.

  2. Fitness Landscapes of Functional RNAs

    Directory of Open Access Journals (Sweden)

    Ádám Kun

    2015-08-01

    Full Text Available The notion of fitness landscapes, a map between genotype and fitness, was proposed more than 80 years ago. For most of this time data was only available for a few alleles, and thus we had only a restricted view of the whole fitness landscape. Recently, advances in genetics and molecular biology allow a more detailed view of them. Here we review experimental and theoretical studies of fitness landscapes of functional RNAs, especially aptamers and ribozymes. We find that RNA structures can be divided into critical structures, connecting structures, neutral structures and forbidden structures. Such characterisation, coupled with theoretical sequence-to-structure predictions, allows us to construct the whole fitness landscape. Fitness landscapes then can be used to study evolution, and in our case the development of the RNA world.

  3. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

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

  4. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

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

  5. Care of HIV-exposed and HIV-infected neonates

    African Journals Online (AJOL)

    However, further reduction in MTCT may be possible if newborns at high risk of acquiring HIV ... infants of breastfeeding mothers with newly diagnosed HIV infection, dual NVP/ .... birth HIV DNA PCR testing for HIV-exposed low birth weight.

  6. Side Effects of HIV Medicines: HIV and Diabetes

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... throughout the body. A hormone called insulin helps move the glucose into the cells. Once in the ...

  7. Leading a Culture of Fitness

    Science.gov (United States)

    2011-03-24

    professional fighting force. Numerous studies indicate physical fitness improves cognitive function, the ability to handle stress, injury recovery...4 ―What is Fitness?‖ The CrossFit Journal (October 2002) http://www.crossfit.com (accessed 11 February, 2011). An excellent article beyond the...scope of this paper. Although our definition was derived from Crossfit , it is our position that Crossfit is not, and should not be, the only method to

  8. Physical Fitness in the Army

    Science.gov (United States)

    1977-03-17

    in fitness as the absence of disease or injury . The coach defines fitness as §l’Jse factors responsible for success in a sport. The leader is...lower back and legs to gradually increase your body’s level of activity. This will reduce the risk of injury and prevent unnecessary soreness. Also, a...flexibility. Let’s discuss the importance of muscular fitness and how we can achieve this kind of fitneas through weightlifting or calisthenics. Remember

  9. Eesti teadlaste HIV-vaktsiini süstitakse katseks aafriklastele / Villu Päärt

    Index Scriptorium Estoniae

    Päärt, Villu, 1972-

    2006-01-01

    Vt. ka Postimees : na russkom jazõke 5. apr., lk. 2. Tartu teadlaste leiutatud ning Soome biotehnoloogiafirma FIT Biotech arendatavat vaktsiini katsetatakse Lõuna-Aafrika Vabariigis 60 surmaviirusega nakatunud inimese peal. Lisa: Eestlaste HIV-vaktsiini senine lugu

  10. Gradual adaptation of HIV to human host populations: good or bad news?

    Science.gov (United States)

    Brander, Christian; Walker, Bruce D

    2003-11-01

    The continuous evolution and adaptation of HIV to its host has produced extensive global viral diversity. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity and pathogenicity will be crucial to the successful design of effective HIV vaccines. Here we discuss some potential scenarios of viral and host coevolution.

  11. Drugs + HIV, Learn the Link

    Medline Plus

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

  12. Global HIV/AIDS Epidemic

    Science.gov (United States)

    ... Policy The Global HIV/AIDS Epidemic The Global HIV/AIDS Epidemic Published: Nov 29, 2017 Facebook Twitter ... 2001-FY 2018 Request The Global Response to HIV/AIDS International efforts to combat HIV began in ...

  13. HIV/AIDS in Women

    Science.gov (United States)

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

  14. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

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

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... contracting or transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug misuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ...

  17. Role of HLA adaptation in HIV evolution

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N.; Leslie, Alasdair; Goulder, Philip

    2016-01-01

    Killing of HIV-infected cells by CD8+ T-cells imposes strong selection pressure on the virus toward escape. The HLA class I molecules that are successful in mediating some degree of control over the virus are those that tend to present epitopes in conserved regions of the proteome, such as in p24...... Gag, in which escape also comes at a significant cost to viral replicative capacity (VRC). In some instances, compensatory mutations can fully correct for the fitness cost of such an escape variant; in others, correction is only partial. The consequences of these events within the HIV-infected host......, and at the population level following transmission of escape variants, are discussed. The accumulation of escape mutants in populations over the course of the epidemic already shows instances of protective HLA molecules losing their impact, and in certain cases, a modest decline in HIV virulence in association...

  18. Living with HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  19. Female Fitness in the Blogosphere

    Directory of Open Access Journals (Sweden)

    Jesper Andreasson

    2013-07-01

    Full Text Available This article analyzes self-portrayals and gender constructions among female personal trainers within an Internet-mediated framework of fitness culture. The empirical material comes from a close examination of three strategically selected blogs. The result shows that some of the blogs clearly build upon what Connell calls emphasized femininity, as a means of legitimizing and constructing appropriate female fitness. In addition, there are also tendencies of sexualization in text and imagery present. As such, these self-representations are framed within a cultural history of body fitness dominated by stereotypical ways of perceiving masculinity and femininity. However, this does not capture the entire presentation of the self among the analyzed fitness bloggers. The blogs also point in the direction of ongoing negotiations and subversions of traditional gender norms. Among other things, they show how irony and humor are used as a means of questioning normative gender constructions while empowering female fitness and bodyliness.

  20. Nuclear fuel element end fitting

    International Nuclear Information System (INIS)

    Jabsen, F.S.

    1980-01-01

    An invention is described whereby end fittings are formed from lattices of mutually perpendicular plates. At the plate intersections, sockets are secured to the end fittings in a manner that permits the longitudinal axes of each of the sockets to align with the respective lines of intersection of the plates. The sockets all protrude above one of the surfaces of the end fitting. Further, a detent is formed in the proturding sides of each of the sockets. Annular grooves are formed in each of the ends of the fuel rods that are to be mounted between the end fittings. The socket detents protrude into the respective annular grooves, thus engaging the grooves and retaining the fuel rods and end fittings in one integral structure. (auth)

  1. FITS Liberator: Image processing software

    Science.gov (United States)

    Lindberg Christensen, Lars; Nielsen, Lars Holm; Nielsen, Kaspar K.; Johansen, Teis; Hurt, Robert; de Martin, David

    2012-06-01

    The ESA/ESO/NASA FITS Liberator makes it possible to process and edit astronomical science data in the FITS format to produce stunning images of the universe. Formerly a plugin for Adobe Photoshop, the current version of FITS Liberator is a stand-alone application and no longer requires Photoshop. This image processing software makes it possible to create color images using raw observations from a range of telescopes; the FITS Liberator continues to support the FITS and PDS formats, preferred by astronomers and planetary scientists respectively, which enables data to be processed from a wide range of telescopes and planetary probes, including ESO's Very Large Telescope, the NASA/ESA Hubble Space Telescope, NASA's Spitzer Space Telescope, ESA's XMM-Newton Telescope and Cassini-Huygens or Mars Reconnaissance Orbiter.

  2. Fitness Doping and Body Management

    DEFF Research Database (Denmark)

    Thualagant, Nicole

    This PhD thesis examines in a first paper the conceptualization of fitness doping and its current limitations. Based on a review of studies on bodywork and fitness doping it is emphasised that the definition of doping does not provide insights into bodywork of both men and women. Moreover......, it is argued that the social and a cultural context are missing in the many epidemiological studies on the prevalence of doping. The second paper explores the difficulties of implementing an anti-doping policy, which was originally formulated in an elite sport context, in a fitness context and more......-based fitness centres. Based on a survey in ten Danish club-based fitness centres and on narratives from semi-structured interviews, it is highlighted that the objectives of bodywork differ according to the users’ age and gender. Two different ways of investing in the body are explored in the paper, namely...

  3. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

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

  4. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Current indirect fitness and future direct fitness are not incompatible.

    Science.gov (United States)

    Brahma, Anindita; Mandal, Souvik; Gadagkar, Raghavendra

    2018-02-01

    In primitively eusocial insects, many individuals function as workers despite being capable of independent reproduction. Such altruistic behaviour is usually explained by the argument that workers gain indirect fitness by helping close genetic relatives. The focus on indirect fitness has left open the question of whether workers are also capable of getting direct fitness in the future in spite of working towards indirect fitness in the present. To investigate this question, we recorded behavioural profiles of all wasps on six naturally occurring nests of Ropalidia marginata , and then isolated all wasps in individual plastic boxes, giving them an opportunity to initiate nests and lay eggs. We found that 41% of the wasps successfully did so. Compared to those that failed to initiate nests, those that did were significantly younger, had significantly higher frequency of self-feeding behaviour on their parent nests but were not different in the levels of work performed in the parent nests. Thus ageing and poor feeding, rather than working for their colonies, constrain individuals for future independent reproduction. Hence, future direct fitness and present work towards gaining indirect fitness are not incompatible, making it easier for worker behaviour to be selected by kin selection or multilevel selection. © 2018 The Author(s).

  6. Opas CrossFit -harjoitteluun

    OpenAIRE

    Knaapi, Matti

    2014-01-01

    CrossFit on laji, joka pyrkii edistämään terveyttä ja kuntoa. CrossFit saleja löytyy mailmalta yli 10 000 kappaletta. CrossFit -harjoittelussa pyritään parantamaan ihmisen kuntoa mahdollisimman laajalla skaalalla kehittämällä mm. voimaa, kestävyyttä, tarkkuutta, tasapainoa ja eri aineenvaihduntareittejä samanaikaisesti. Terveyden ja kunnon kehittämiseen kuuluu kuntoilun lisäksi myös muita osa-alueita. Ruokavalio ja kehonhuolto ovat tärkeitä osa-alueita hyvän kunnon saavuttamiseksi. Ruokav...

  7. Respirators. Does your face fit

    Energy Technology Data Exchange (ETDEWEB)

    Caro, N M; Else, D

    1981-04-01

    The authors carried out a survey of face sizes of men and women of four different ethnic origins and carried out face-seal leakage trials on four corresponding test panels. No single respirator design is likely to fit all members of the workforce, and it may be necessary to stock respirators from more than one manufacturers.Three or four different respirators or size of respirator may be needed. However, the use of lossely-fitting respirators such as Airsteam helmets could remove the necessity for exhaustive fitting procedures.

  8. Design and expression of a short peptide as an HIV detection probe

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Jamie A.; Yu, Zhiqiang; Dedkova, Larisa M.; Chen, Shengxi, E-mail: shengxi.chen.1@asu.edu

    2014-01-03

    Highlights: •We designed a short fusion peptide (FP-50) for in vivo expression. •This peptide is a very promising component for detection of gp120 protein. •The detectable level is about 20–200 times lower than previously published methods. •It is a novel probe to detect HIV-1 gp120 during early stages of HIV infection. -- Abstract: To explore a low-cost novel probe for HIV detection, we designed and prepared a 50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The detectable level of gp120 protein using the FP-50 peptide was approximately 20–200 times lower than previously published methods that used a pair of monoclonal antibodies. Thus, this short peptide is a very promising component for detection of gp120 protein during early stages of HIV infection.

  9. HIV and Hepatitis C

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis C Last Reviewed: July 25, 2017 ...

  10. HIV/AIDS Basics

    Science.gov (United States)

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

  11. HIV and Tuberculosis (TB)

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Tuberculosis (TB) Last Reviewed: June 14, 2018 ...

  12. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis B Last Reviewed: July 24, 2017 ...

  13. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    infected community and can severely hamper thrombopoietin production, due to liver damage. HIV and platelets. Thrombocytopenia in HIV was first described in 1982. The prevalence is more or less 40%, depending on which ...

  14. HIV Resistance Testing

    Science.gov (United States)

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

  15. HIV: Treatment and Comorbidity

    NARCIS (Netherlands)

    C. Rokx (Casper)

    2016-01-01

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

  16. Testing for HIV

    Science.gov (United States)

    ... 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 ...

  17. Pregnancy and HIV

    Science.gov (United States)

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

  18. Kinematic Fitting of Detached Vertices

    Energy Technology Data Exchange (ETDEWEB)

    Mattione, Paul [Rice Univ., Houston, TX (United States)

    2007-05-01

    The eg3 experiment at the Jefferson Lab CLAS detector aims to determine the existence of the $\\Xi_{5}$ pentaquarks and investigate the excited $\\Xi$ states. Specifically, the exotic $\\Xi_{5}^{--}$ pentaquark will be sought by first reconstructing the $\\Xi^{-}$ particle through its weak decays, $\\Xi^{-}\\to\\pi^{-}\\Lambda$ and $\\Lambda\\to\\pi^{-}$. A kinematic fitting routine was developed to reconstruct the detached vertices of these decays, where confidence level cuts on the fits are used to remove background events. Prior to fitting these decays, the exclusive reaction $\\gamma D\\rightarrow pp\\pi^{-}$ was studied in order to correct the track measurements and covariance matrices of the charged particles. The $\\Lambda\\rightarrow p\\pi^{-}$ and $\\Xi^{-}\\to\\pi^{-}\\Lambda$ decays were then investigated to demonstrate that the kinematic fitting routine reconstructs the decaying particles and their detached vertices correctly.

  19. ORIGINAL ARTICLES Atopy in HIV-infected children in Pretoria

    African Journals Online (AJOL)

    Both atopic and HIV-related diseases are common in South. Africa. Atopy is a genetic .... tree mix, dog hair dander, cat hair dander, standard mite .... incidence of dermatitis;16 this may present as inflammatory or eczematous .... during intestinal nematode infections: what it takes to make a Th2 cell in vivo. Immunol Rev. 2004 ...

  20. Statistical topography of fitness landscapes

    OpenAIRE

    Franke, Jasper

    2011-01-01

    Fitness landscapes are generalized energy landscapes that play an important conceptual role in evolutionary biology. These landscapes provide a relation between the genetic configuration of an organism and that organism’s adaptive properties. In this work, global topographical features of these fitness landscapes are investigated using theoretical models. The resulting predictions are compared to empirical landscapes. It is shown that these landscapes allow, at least with respe...

  1. Desirable design of hose fittings

    DEFF Research Database (Denmark)

    Voigt, Kristian

    1998-01-01

    This paper describes the primary functionality of a hose fitting. There has been made a discussion about the different parts of the hose assembly - the nipple, the hose and the outer compression parts. The last subject covered is which criteria should be put up for determining what is a good hose...... fittings. There has been made an uncompleted list of 'Voice of Customer' to this respect. Observations and interviews in industry should expand this list....

  2. The 'fitting problem' in cosmology

    International Nuclear Information System (INIS)

    Ellis, G.F.R.; Stoeger, W.

    1987-01-01

    The paper considers the best way to fit an idealised exactly homogeneous and isotropic universe model to a realistic ('lumpy') universe; whether made explicit or not, some such approach of necessity underlies the use of the standard Robertson-Walker models as models of the real universe. Approaches based on averaging, normal coordinates and null data are presented, the latter offering the best opportunity to relate the fitting procedure to data obtainable by astronomical observations. (author)

  3. The HIV Airway

    African Journals Online (AJOL)

    Adele

    dren living with HIV/AIDS. Annual national antenatal surveil- lance shows an HIV prevalence of 26.5% among pregnant women. Anaesthetists are confronted with an increasing number of HIV infected patients, presenting for both emergency and elective sur- gery. They range from having asymptomatic infection to end stage.

  4. HIV/AIDS

    Science.gov (United States)

    ... Key populations are groups who are at increased risk of HIV irrespective of epidemic type or local context. They include: men who have sex with men, ... HIV testing and counselling; HIV treatment and care; risk-reduction ... management of STIs, tuberculosis and viral hepatitis. Elimination of ...

  5. HIV Antibody Test

    Science.gov (United States)

    ... 65 in the case of the USPSTF) and pregnant women be screened for HIV at least once. The CDC and American College ... to make sure she is not infected with HIV before getting pregnant may opt to get tested (see Pregnancy: HIV .) ...

  6. Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

    Energy Technology Data Exchange (ETDEWEB)

    Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl

    2016-01-15

    Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

  7. Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Christopher W Pohlmeyer

    Full Text Available Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.

  8. HIV-Specific CD8+ T Cell-Mediated Viral Suppression Correlates With the Expression of CD57

    DEFF Research Database (Denmark)

    Jensen, Sanne S; Tingstedt, Jeanette Linnea; Larsen, Tine Kochendorf

    2016-01-01

    BACKGROUND: Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44...

  9. Measured, modeled, and causal conceptions of fitness

    Science.gov (United States)

    Abrams, Marshall

    2012-01-01

    This paper proposes partial answers to the following questions: in what senses can fitness differences plausibly be considered causes of evolution?What relationships are there between fitness concepts used in empirical research, modeling, and abstract theoretical proposals? How does the relevance of different fitness concepts depend on research questions and methodological constraints? The paper develops a novel taxonomy of fitness concepts, beginning with type fitness (a property of a genotype or phenotype), token fitness (a property of a particular individual), and purely mathematical fitness. Type fitness includes statistical type fitness, which can be measured from population data, and parametric type fitness, which is an underlying property estimated by statistical type fitnesses. Token fitness includes measurable token fitness, which can be measured on an individual, and tendential token fitness, which is assumed to be an underlying property of the individual in its environmental circumstances. Some of the paper's conclusions can be outlined as follows: claims that fitness differences do not cause evolution are reasonable when fitness is treated as statistical type fitness, measurable token fitness, or purely mathematical fitness. Some of the ways in which statistical methods are used in population genetics suggest that what natural selection involves are differences in parametric type fitnesses. Further, it's reasonable to think that differences in parametric type fitness can cause evolution. Tendential token fitnesses, however, are not themselves sufficient for natural selection. Though parametric type fitnesses are typically not directly measurable, they can be modeled with purely mathematical fitnesses and estimated by statistical type fitnesses, which in turn are defined in terms of measurable token fitnesses. The paper clarifies the ways in which fitnesses depend on pragmatic choices made by researchers. PMID:23112804

  10. HIV antibodies for treatment of HIV infection.

    Science.gov (United States)

    Margolis, David M; Koup, Richard A; Ferrari, Guido

    2017-01-01

    The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  11. Comparing Person Organization Fit and Person Job Fit

    Directory of Open Access Journals (Sweden)

    Kadir Ardıç

    2016-07-01

    Full Text Available Although there have been many studies conducted to analyze the effects of person-organization fit (POF and person-job fit (PJF on individual outcomes, little is known about which of these fit associates stronger with individual variables (i.e., intention to quit job, IQJ, and perceived individual performance, PIP. Therefore the purpose of the study is to compare the relationships of PJF and POF with IQJ and PIP. The sample of the study consists of security guards working at a private company's civil aviation safety department. Totally 98 security guards participated to the research. Results indicated that, the relationships of PJF and POF with IQJ and PIP were not significantly different. Consequently the results indicate that POF and PJF associate similarly with critical individual outcomes.

  12. Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

    Directory of Open Access Journals (Sweden)

    Mohamed Abdel-Mohsen

    2016-06-01

    Full Text Available Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART, and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9 potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002, more potently than vorinostat (p = 0.02. rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05. rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006 and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02 and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009, suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies.

  13. Towards HIV-1 remission: potential roles for broadly neutralizing antibodies.

    Science.gov (United States)

    Halper-Stromberg, Ariel; Nussenzweig, Michel C

    2016-02-01

    Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.

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

    Science.gov (United States)

    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.

  15. Understanding HIV-related posttraumatic stress disorder in South Africa: a review and conceptual framework.

    Science.gov (United States)

    Young, Charles

    2011-06-01

    A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic review of the literature identified eight relevant studies that put current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%. Even the lower estimates suggest that PTSD in response to the trauma of being diagnosed and living with HIV is a significant mental health burden. However, a conceptual framework to advance our understanding of the prevalence and phenomenology of HIV-related PTSD is lacking. This article argues that the Ehlers & Clark (2000) cognitive model of PTSD provides a useful conceptual framework for understanding HIV-related PTSD in South Africa. The model emphasises the role of trauma appraisals in the development and maintenance of PTSD, which can also be usefully applied to some of the other psychological disorders associated with HIV infection. The model appears to fit some of the important research findings, and it offers insights into the relationships between HIV-related PTSD and other psychological disorders, HIV stigma, the high prevalence of non-HIV traumatic events, occasional problems with the delivery of antiretroviral drugs in the South African public health service, the unpredictable course of HIV illness, and the quality of HIV testing and counselling. Implications for individual treatment strategies and broader public health interventions are briefly discussed.

  16. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

    Science.gov (United States)

    2018-01-01

    ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

  17. Frequencies of HBV, HCV, HIV, and Syphilis Markers Among Blood ...

    African Journals Online (AJOL)

    Purpose: This study aimed to determine the frequency rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis among blood donors. Methods: Physically fit persons aged 18 – 48 years who came for blood donation at the blood bank unit of the military hospital in Hodeidah, ...

  18. Redefining the Viral Reservoirs That Prevent HIV-1 Eradication

    Science.gov (United States)

    Eisele, Evelyn; Siliciano, Robert F.

    2014-01-01

    Summary This review proposes definitions for key terms in the field of HIV-1 latency and eradication. In the context of eradication, a reservoir is a cell type that allows persistence of replication-competent HIV-1 on a time scale of years in patients on optimal antiretroviral therapy. Reservoirs act as a barrier to eradication in the patient population in whom cure attempts will likely be made. Halting viral replication is essential to eradication, and definitions and criteria for assessing whether this goal has been achieved are proposed. The cell types that may serve as reservoirs for HIV-1 are discussed. Currently, only latently infected resting CD4+ T cells fit the proposed definition of a reservoir, and more evidence is necessary to demonstrate that other cell types including hematopoietic stem cells and macrophages fit this definition. Further research is urgently required on potential reservoirs in the gut-associated lymphoid tissue and the central nervous system. PMID:22999944

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  1. Humanized mice: models for evaluating NeuroHIV and cure strategies.

    Science.gov (United States)

    Honeycutt, Jenna B; Garcia, J Victor

    2018-04-01

    While the human immunodeficiency virus (HIV) epidemic was initially characterized by a high prevalence of severe and widespread neurological pathologies, the development of better treatments to suppress viremia over years and even decades has mitigated many of the severe neurological pathologies previously observed. Despite effective treatment, mild neurocognitive impairment and premature cognitive aging are observed in HIV-infected individuals, suggesting a changing but ongoing role of HIV infection in the central nervous system (CNS). Although current therapies are effective in suppressing viremia, they are not curative and patients must remain on life-long treatment or risk recrudescence of virus. Important for the development and evaluation of a cure for HIV will be animal models that recapitulate critical aspects of infection in vivo. In the following, we seek to summarize some of the recent developments in humanized mouse models and their usefulness in modeling HIV infection of the CNS and HIV cure strategies.

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

    Science.gov (United States)

    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.

  3. Experiences of condom fit and feel among African-American men who have sex with men.

    Science.gov (United States)

    Reece, Michael; Dodge, Brian; Herbenick, Debby; Fisher, Christopher; Alexander, Andreia; Satinsky, Sonya

    2007-10-01

    To offer an empirical understanding of characteristics associated with the fit and feel of condoms among African-American men who have sex with men (MSM), a particularly high-risk group for HIV and other sexually transmitted infections (STI) in the United States. Survey data were collected from 178 adult African-American MSM attending a community event in Atlanta, Georgia. Although the majority of participants reported that condoms generally fit properly and felt comfortable, a substantial number of men reported a variety of problems with the fit and feel of condoms. Specifically, 21% reported that condoms felt too tight, 18% reported that condoms felt too short, 10% reported that condoms felt too loose, and 7% reported that condoms felt too long. There were significant associations between men's reports of condom breakage and slippage, and their perceptions of condom fit and feel. Perceptions of condom fit and feel were also related to men's reports of seeking condoms for their size-specific properties. The fit and feel issues that men in this sample identified may be among those that contribute to their likelihood of using, or not using, condoms consistently and correctly. A better understanding of these factors will be beneficial to both condom manufacturers and sexual health professionals who share a common goal of increasing consistent and correct condom use and reducing the incidence of HIV and other STI among this and other communities.

  4. Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

    Science.gov (United States)

    Bomsel, Morgane; Ganor, Yonatan

    2017-12-01

    The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

  5. The FitTrack Index as fitness indicator

    African Journals Online (AJOL)

    Dina Christina Janse van Rensburg

    d Institute for Sports Research, Faculty of Humanities, University of Pretoria, South Africa e Institute for Food ... The American College of Sports Medicine's guidelines for health/fitness .... It is important to stress that the focus of this study was not.

  6. Seeking HIV prevention strategies for women.

    Science.gov (United States)

    Townsend, S

    1993-05-01

    Women are biologically more susceptible to HIV infection than men through heterosexual penile-vaginal intercourse, and transmission by heterosexual means seems to be increasing. The use of male condoms and partner reduction are currently recommended to reduce the risk of contracting and transmitting HIV. Women can, however, only indirectly influence these behaviors. Many face social and emotional factors which make it impossible to negotiate condom use with an unwilling partner. Scientists are therefore paying greater attention to female barrier methods such as the female condom and spermicides as potential female- controlled ways to help women avoid infection. Noncontraceptive chemical methods in the form of jellies and topical creams are being explored. Limited in vivo scientific data exists on how these methods may prevent the transmission of HIV. The female condom is a thin, plastic sheath which covers the cervix, vagina, and women's external genitalia. It has gone to clinical trials in 1700 women at 71 sites. While many women are in favor of the method, objections to its use have been voiced due to its appearance, the noise made during intercourse, slippage, how it feels during intercourse, expense, reduced sensitivity, and embarrassment. Its potential for re-use must be explored. Only inconclusive results are available on the effectiveness of spermicides. While lab and animal research show nonoxynol-9 can kill HIV, it remains to be seen how much or how often it may be used before mucosal linings become irritated and potentially facilitate the entry of HIV. Many unresolved questions about the mechanics of HIV infection remain to be answered before these methods may be fully endorsed by a wide array of scientists.

  7. HIV-1 Eradication Strategies: Design and Assessment

    Science.gov (United States)

    Siliciano, Robert F.

    2014-01-01

    Purpose of review Recent developments have generated renewed interest in the possibility of curing HIV-1 infection. This review describes some of the practical challenges that will need to be overcome if curative strategies are to be successful. Recent findings The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing the infection. The most widely discussed approach to curing the infection involves finding agents that reverse latency in resting CD4+ T cells, with the assumption that the cells will then die from viral cytopathic effects or be lysed by host cytolytic T lymphocytes (CTL). A major challenge is the development of in vitro models that can be used to explore mechanisms and identify latency reversing agents (LRA). Although several models have been developed, including primary cell models, none of them may fully capture the quiescent state of the cells that harbor latent HIV-1 in vivo. An additional problem is that LRA that do not cause T cell activation may not lead to the death of infected cells. Finally, measuring the effects of LRAs in vivo is complicated by the lack of correlation between different assays for the latent reservoir. Summary Progress on these practical issues is essential to finding a cure. PMID:23698561

  8. Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders.

    Science.gov (United States)

    Wrasidlo, Wolf; Crews, Leslie A; Tsigelny, Igor F; Stocking, Emily; Kouznetsova, Valentina L; Price, Diana; Paulino, Amy; Gonzales, Tania; Overk, Cassia R; Patrick, Christina; Rockenstein, Edward; Masliah, Eliezer

    2014-12-01

    Anti-retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood-brain barrier. We screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV-gp120 neurotoxicity. Among 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 μM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology. Compounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders. © 2014 The British Pharmacological Society.

  9. HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations.

    Science.gov (United States)

    Aulicino, Paula C; Rocco, Carlos A; Mecikovsky, Debora; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

    2010-01-01

    Patterns and pathways of HIV type-1 (HIV-1) antiretroviral (ARV) drug resistance-associated mutations in clinical isolates are conditioned by ARV history and factors such as viral subtype and fitness. Our aim was to analyse the frequency and association of ARV drug resistance mutations in a group of long-term vertically infected patients from Argentina. Plasma samples from 71 patients (38 children and 33 adolescents) were collected for genotypic HIV-1 ARV resistance testing during the period between February 2006 and October 2008. Statistically significant pairwise associations between ARV resistance mutations in pol, as well as associations between mutations and drug exposure, were identified using Fisher's exact tests with Bonferroni and false discovery rate corrections. Phylogenetic analyses were performed for subtype assignment. In protease (PR), resistance-associated mutations M46I/L, I54M/L/V/A/S and V82A/F/T/S/M/I were associated with each other and with minor mutations at codons 10, 24 and 71. Mutations V82A/F/T/S/M/I were primarily selected by the administration of ritonavir (RTV) in an historical ARV regimen. In reverse transcriptase, thymidine analogue mutation (TAM)1 profile was more common than TAM2. The non-nucleoside K103N+L100I mutations were observed at high frequency (15.5%) and were significantly associated with the nucleoside mutation L74V in BF recombinants. Associations of mutations at PR sites reflect the frequent use of RTV at an early time in this group of patients and convergent resistance mechanisms driven by the high exposure to protease inhibitors, as well as local HIV-1 diversity. The results provide clinical evidence of a molecular interaction between K103N+L100I and L74V mutations at the reverse transcriptase gene in vivo, limiting the future use of second-generation non-nucleoside reverse transcriptase inhibitors such as etravirine.

  10. Decision making on fitness landscapes

    Science.gov (United States)

    Arthur, R.; Sibani, P.

    2017-04-01

    We discuss fitness landscapes and how they can be modified to account for co-evolution. We are interested in using the landscape as a way to model rational decision making in a toy economic system. We develop a model very similar to the Tangled Nature Model of Christensen et al. that we call the Tangled Decision Model. This is a natural setting for our discussion of co-evolutionary fitness landscapes. We use a Monte Carlo step to simulate decision making and investigate two different decision making procedures.

  11. Adaptive Management Fitness of Watersheds

    Directory of Open Access Journals (Sweden)

    Ignacio Porzecanski

    2012-09-01

    Full Text Available Adaptive management (AM promises to improve our ability to cope with the inherent uncertainties of managing complex dynamic systems such as watersheds. However, despite the increasing adherence and attempts at implementation, the AM approach is rarely successful in practice. A one-size-fits-all AM strategy fails because some watersheds are better positioned at the outset to succeed at AM than others. We introduce a diagnostic tool called the Index of Management Condition (IMC and apply it to twelve diverse watersheds in order to determine their AM "fitness"; that is, the degree to which favorable adaptive management conditions are in place in a watershed.

  12. Physical Work Demands and Fitness

    DEFF Research Database (Denmark)

    Larsen, Mette Korshøj

    . The effects were evaluated with objective physiological or diurnal data in an intention-to-treat analysis using multi-adjusted mixed models. The results indicated that the intervention led to several improvements in risk factors for cardiovascular disease, e.g. enhanced cardiorespiratory fitness, reduced...... exposed to high relative aerobic workloads obtained more pronounced increases of resting and 24-hour ambulatory blood pressure, an unaltered cardiorespiratory fitness and a reduced sleeping heart rate. The enhanced resting and 24-hour ambulatory blood pressure may be explained as a potential...

  13. The Andersen aerobic fitness test

    DEFF Research Database (Denmark)

    Aadland, Eivind; Terum, Torkil; Mamen, Asgeir

    2014-01-01

    BACKGROUND: High aerobic fitness is consistently associated with a favorable metabolic risk profile in children. Direct measurement of peak oxygen consumption (VO2peak) is often not feasible, thus indirect tests such as the Andersen test are required in many settings. The present study seeks...... of agreement) were 26.7±125.2 m for test 2 vs. test 1 (pfit in the present sample; thus, we suggest a new equation: VO2peak = 23....... Researchers should be aware of the amount of noise in indirect tests that estimate aerobic fitness....

  14. Decision Making on Fitness Landscapes

    DEFF Research Database (Denmark)

    Arthur, Rudy; Sibani, Paolo

    2017-01-01

    We discuss fitness landscapes and how they can be modified to account for co-evolution. We are interested in using the landscape as a way to model rational decision making in a toy economic system. We develop a model very similar to the Tangled Nature Model of Christensen et. al. that we call...... the Tangled Decision Model. This is a natural setting for our discussion of co-evolutionary fitness landscapes. We use a Monte Carlo step to simulate decision making and investigate two different decision making procedures....

  15. Contribution of HIV minority variants to drug resistance in an integrase strand transfer inhibitor-based therapy

    Czech Academy of Sciences Publication Activity Database

    Weber, Jan; Gibson, R. M.; Meyer, A. M.; Winner, D.; Robertson, D. L.; Miller, M. D.; Quinones-Mateu, M. E.

    2013-01-01

    Roč. 18, Suppl. 1 (2013), A66-A66 ISSN 1359-6535. [International Workshop on HIV & Hepatitis Virus Drug Resistance Curative Strategies. 04.06.2013-08.06.2013, Toronto] Institutional support: RVO:61388963 Keywords : HIV minority variants * integrase inhibitor * replicative fitness Subject RIV: CE - Biochemistry

  16. Correlates of HIV infection among people visiting public HIV ...

    African Journals Online (AJOL)

    Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, ... Background: HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. ... AJOL African Journals Online.

  17. HIV/AIDS in Women - Multiple Languages

    Science.gov (United States)

    ... medicines and women - HIV medicines, part 7 - English MP3 HIV medicines and women - HIV medicines, part 7 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 HIV medicines and women - HIV medicines, part 7 - ...

  18. CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

    Science.gov (United States)

    Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith; Spivak, Adam M; Nell, Racheal A; Tomescu, Costin; Vadrevu, Surya Kumari; Giron, Leila B; Serra-Peinado, Carla; Genescà, Meritxell; Castellví, Josep; Wu, Guoxin; Del Rio Estrada, Perla M; González-Navarro, Mauricio; Lynn, Kenneth; King, Colin T; Vemula, Sai; Cox, Kara; Wan, Yanmin; Li, Qingsheng; Mounzer, Karam; Kostman, Jay; Frank, Ian; Paiardini, Mirko; Hazuda, Daria; Reyes-Terán, Gustavo; Richman, Douglas; Howell, Bonnie; Tebas, Pablo; Martinez-Picado, Javier; Planelles, Vicente; Buzon, Maria J; Betts, Michael R; Montaner, Luis J

    2018-04-18

    The persistence of HIV reservoirs, including latently infected, resting CD4 + T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4 + T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4 + T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV + or SIV + subjects, we found that most of the circulating memory CD32 + CD4 + T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a T H 2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4 + T cells in peripheral blood or lymphoid tissue; isolated CD32 + resting CD4 + T cells accounted for less than 3% of the total HIV DNA in CD4 + T cells. Cell-associated HIV DNA and RNA loads in CD4 + T cells positively correlated with the frequency of CD32 + CD69 + CD4 + T cells but not with CD32 expression on resting CD4 + T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4 + T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4 + T cells enriched for transcriptionally active HIV after long-term ART. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  19. Human antibodies that neutralize primary human immunodeficiency virus type 1 in vitro do not provide protection in an in vivo model.

    NARCIS (Netherlands)

    M. Schutten (Martin); K. Tenner-Racz; P. Racz; D.W. van Bekkum (Dirk); A.D.M.E. Osterhaus (Albert)

    1996-01-01

    textabstractRecently, conflicting data have been published about the ability of antibodies which efficiently neutralize T cell-adapted human immunodeficiency virus type 1 (HIV-1) strains to neutralize primary HIV-1 strains in vitro and in vivo. Here we present data indicating that such antibodies

  20. Broadening of coreceptor usage by human immunodeficiency virus type 2 does not correlate with increased pathogenicity in an in vivo model.

    NARCIS (Netherlands)

    M.E. van der Ende (Marchina); C. Guillon (Christophe); P.H.M. Boers (Patrick); R.A. Gruters (Rob); P. Racz; K. Tenner-Racz; A.D.M.E. Osterhaus (Albert); M. Schutten (Martin)

    2000-01-01

    textabstractThe pathogenic properties of four primary human immunodeficiency virus type 2 (HIV-2) isolates and two primary HIV-2 biological clones were studied in an in vivo human-to-mouse chimeric model. The cell-associated viral load and the ability to reduce the severity of the induced

  1. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains.

    Science.gov (United States)

    Popp, Christina; Hampe, Irene A I; Hertlein, Tobias; Ohlsen, Knut; Rogers, P David; Morschhäuser, Joachim

    2017-07-01

    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host. Copyright © 2017 American Society for Microbiology.

  2. HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

    Science.gov (United States)

    Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

    2017-09-15

    Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Molecular Basis for Drug Resistance in HIV-1 Protease

    Directory of Open Access Journals (Sweden)

    Celia A. Schiffer

    2010-11-01

    Full Text Available HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease’s function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.

  4. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.

    Science.gov (United States)

    Almeida, Jorge R; Sauce, Delphine; Price, David A; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C; Autran, Brigitte; Sáez-Cirión, Asier; Appay, Victor

    2009-06-18

    CD8(+) T cells are major players in the immune response against HIV. However, recent failures in the development of T cell-based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell-mediated efficacy. CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8(+) T cells from infected donors. We report that attributes of CD8(+) T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy.

  5. Physical Fitness: Get Your Body Moving

    Science.gov (United States)

    Physical Fitness: Get Your Body Moving; Exercise; does exercise help quit smoking; exercises after quitting smoking; exercise after smoking; exercise and quitting smoking; exercise and smoking; smoking articles; articles about smoking; articles on smoking; articles about smoking; article on smoking; health articles on smoking; smoking article; benefits of physical activity; benefits for physical activity; benefit of physical activity; benefits to physical activity; daily physical activities; daily physical activity; healthy physical activities; healthy physical activity; health activities; activity for health; exercise physical activity and health; health activities; health activities for kids; health and fitness activities; health benefits for physical activity; health benefits from physical activity; health benefits of physical activity; health benefits physical activity; health promotion activities; physical exercise; exercise and physical activity; exercise and physical health; exercise for physical fitness; health benefits of physical fitness; how to do physical exercise; physical activity and exercise; physical activity exercise; physical health; physical health and fitness; physical health and wellness; physical health benefits; physical Health fitness; what are the benefits of physical fitness; physical fitness; about physical fitness; benefits of physical fitness; how to improve physical fitness; physical fitness; physical fitness article; fitness; fitness article; fitness articles; fitness plans; health and fitness; exercise; benefits of regular exercise on health; exercise plan; exercise tips; routine; best work out routine for overweight women

  6. Sports Potentials for Physical Fitness.

    Science.gov (United States)

    Clarke, H. Harrison, Ed.

    1978-01-01

    This report, one of a series on research into specific physical activities and their efficacy in improving and maintaining physical fitness, examines sport participation and the potential it has for developing muscular strength, muscular endurance, and circulatory-respiratory endurance. The activities consist primarily of the following twelve…

  7. Civilian Fitness: A Readiness Enabler

    Science.gov (United States)

    2008-03-24

    bonus to make working out convenient and facilitate work / life balance . This was secondary to the hope that a fitness program would produce healthier...workforce; and 3) become an employer of choice and promote work life balance .88 34 Strategic plans and supporting objectives of the Army Installation

  8. Hotels Make Room for Fitness.

    Science.gov (United States)

    Koszuta, Laurie Einstein

    1986-01-01

    Hotels, in hopes of gaining a competitive edge, are offering workout rooms, exercise equipment, fitness trails, and jogging tracks, but no standards have been set for safety of the facilities or staff preparedness in exercise screening, equipment use, injury prevention, or first aid. (MT)

  9. Factors Influencing Physical Fitness Evaluation.

    Science.gov (United States)

    Haarer, Barbara G.

    This annotated bibliography focuses on works that examine areas in which the physical educator can improve the administration of physical fitness tests in the elementary and secondary schools. The first part contains annotations that examine modifications of existing components which measure aspects of muscular and cardiovascular endurance. The…

  10. In a Peak Fitness Condition?

    DEFF Research Database (Denmark)

    Storm, Rasmus K.; Nielsen, Klaus

    2010-01-01

    managerial efforts with regard to Danish elite sports? The analysis finds the Danish elite sports organization, Team Danmark, well prepared and fit for the future challenges. Still, though, areas such as talent identification and development and division of roles and responsibilities, are in need...

  11. Inclusive fitness theory and eusociality

    DEFF Research Database (Denmark)

    Abbot, P.; Wrangham, R.; Abe, J.

    2011-01-01

    Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However...

  12. Self-reported cardiorespiratory fitness

    DEFF Research Database (Denmark)

    Holtermann, Andreas; Marott, Jacob Louis; Gyntelberg, Finn

    2015-01-01

    BACKGROUND: The predictive value and improved risk classification of self-reported cardiorespiratory fitness (SRCF), when added to traditional risk factors on cardiovascular disease (CVD) and longevity, are unknown. METHODS AND RESULTS: A total of 3843 males and 5093 females from the Copenhagen...

  13. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  14. Case Report: HIV test misdiagnosis

    African Journals Online (AJOL)

    Case Study: HIV test misdiagnosis 124. Case Report: HIV ... A positive rapid HIV test does not require ... 3 College of Medicine - Johns Hopkins Research Project, Blantyre,. Malawi ... test results: a pilot study of three community testing sites.

  15. HIV/AIDS and Alcohol

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). The U.S. CDC reported that in 2015, 39, ...

  16. Living with HIV/AIDS

    Science.gov (United States)

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

  17. HIV, AIDS, and the Future

    Science.gov (United States)

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

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ... not just injection) can put a person at risk for getting HIV. Drug and alcohol intoxication affect ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

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

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... can suppress the virus and prevent or decrease symptoms of illness. To learn about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease ... About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, GA: CDC, DHHS. Retrieved November ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people ... years, HIV is no longer a death sentence, as it was when the epidemic began. This is ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

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

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the spread of HIV infection in the United States. Drugs can change the way the brain works, ... about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids- ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... in the spread of HIV infection in the United States. Drugs can change the way the brain works, ... learn about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids- ...

  8. A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Carmen H Logie

    Full Text Available African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV-positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health. We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39 of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self-rated health. The model fit the data well: χ2 (45, n = 154 = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance

  9. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

    Science.gov (United States)

    Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H

    2000-10-20

    To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

  10. ACCELERATED FITTING OF STELLAR SPECTRA

    Energy Technology Data Exchange (ETDEWEB)

    Ting, Yuan-Sen; Conroy, Charlie [Harvard–Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Rix, Hans-Walter [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany)

    2016-07-20

    Stellar spectra are often modeled and fitted by interpolating within a rectilinear grid of synthetic spectra to derive the stars’ labels: stellar parameters and elemental abundances. However, the number of synthetic spectra needed for a rectilinear grid grows exponentially with the label space dimensions, precluding the simultaneous and self-consistent fitting of more than a few elemental abundances. Shortcuts such as fitting subsets of labels separately can introduce unknown systematics and do not produce correct error covariances in the derived labels. In this paper we present a new approach—Convex Hull Adaptive Tessellation (chat)—which includes several new ideas for inexpensively generating a sufficient stellar synthetic library, using linear algebra and the concept of an adaptive, data-driven grid. A convex hull approximates the region where the data lie in the label space. A variety of tests with mock data sets demonstrate that chat can reduce the number of required synthetic model calculations by three orders of magnitude in an eight-dimensional label space. The reduction will be even larger for higher dimensional label spaces. In chat the computational effort increases only linearly with the number of labels that are fit simultaneously. Around each of these grid points in the label space an approximate synthetic spectrum can be generated through linear expansion using a set of “gradient spectra” that represent flux derivatives at every wavelength point with respect to all labels. These techniques provide new opportunities to fit the full stellar spectra from large surveys with 15–30 labels simultaneously.

  11. Self-Fitting Hearing Aids

    Directory of Open Access Journals (Sweden)

    Gitte Keidser

    2016-04-01

    Full Text Available A self-contained, self-fitting hearing aid (SFHA is a device that enables the user to perform both threshold measurements leading to a prescribed hearing aid setting and fine-tuning, without the need for audiological support or access to other equipment. The SFHA has been proposed as a potential solution to address unmet hearing health care in developing countries and remote locations in the developed world and is considered a means to lower cost and increase uptake of hearing aids in developed countries. This article reviews the status of the SFHA and the evidence for its feasibility and challenges and predicts where it is heading. Devices that can be considered partly or fully self-fitting without audiological support were identified in the direct-to-consumer market. None of these devices are considered self-contained as they require access to other hardware such as a proprietary interface, computer, smartphone, or tablet for manipulation. While there is evidence that self-administered fitting processes can provide valid and reliable results, their success relies on user-friendly device designs and interfaces and easy-to-interpret instructions. Until these issues have been sufficiently addressed, optional assistance with the self-fitting process and on-going use of SFHAs is recommended. Affordability and a sustainable delivery system remain additional challenges for the SFHA in developing countries. Future predictions include a growth in self-fitting products, with most future SFHAs consisting of earpieces that connect wirelessly with a smartphone and providers offering assistance through a telehealth infrastructure, and the integration of SFHAs into the traditional hearing health-care model.

  12. Selection dramatically reduces effective population size in HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Mittler John E

    2008-05-01

    Full Text Available Abstract Background In HIV-1 evolution, a 100–100,000 fold discrepancy between census size and effective population size (Ne has been noted. Although it is well known that selection can reduce Ne, high in vivo mutation and recombination rates complicate attempts to quantify the effects of selection on HIV-1 effective size. Results We use the inbreeding coefficient and the variance in allele frequency at a linked neutral locus to estimate the reduction in Ne due to selection in the presence of mutation and recombination. With biologically realistic mutation rates, the reduction in Ne due to selection is determined by the strength of selection, i.e., the stronger the selection, the greater the reduction. However, the dependence of Ne on selection can break down if recombination rates are very high (e.g., r ≥ 0.1. With biologically likely recombination rates, our model suggests that recurrent selective sweeps similar to those observed in vivo can reduce within-host HIV-1 effective population sizes by a factor of 300 or more. Conclusion Although other factors, such as unequal viral reproduction rates and limited migration between tissue compartments contribute to reductions in Ne, our model suggests that recurrent selection plays a significant role in reducing HIV-1 effective population sizes in vivo.

  13. Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients

    Science.gov (United States)

    Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu

    2015-01-01

    Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4+ T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM increased HIV-1 integration in CD4+ T cells in a dose-dependent manner. As integration can be modulated by several early postentry steps of HIV-1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV-1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4+ T cells and localize to the nucleus-. In summary, our data provide strong evidence that cocaine can increase HIV-1 integration in CD4+ T cells. Therefore, we hypothesize that increased HIV-1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug-abusing HIV-1 patients. PMID:25691383

  14. The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection

    Science.gov (United States)

    Liu, Cindy M.; Osborne, Brendan J. W.; Hungate, Bruce A.; Shahabi, Kamnoosh; Huibner, Sanja; Lester, Richard; Dwan, Michael G.; Kovacs, Colin; Contente-Cuomo, Tania L.; Benko, Erika; Aziz, Maliha

    2014-01-01

    Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission. PMID:25058515

  15. The semen microbiome and its relationship with local immunology and viral load in HIV infection.

    Directory of Open Access Journals (Sweden)

    Cindy M Liu

    2014-07-01

    Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2  = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

  16. Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

    Science.gov (United States)

    Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

    2018-05-02

    Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

  17. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.

    Directory of Open Access Journals (Sweden)

    Alyson C Yoder

    2017-02-01

    Full Text Available Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a

  18. Cervical Screening within HIV Care: Findings from an HIV-Positive Cohort in Ukraine

    Science.gov (United States)

    Bailey, Heather; Thorne, Claire; Semenenko, Igor; Malyuta, Ruslan; Tereschenko, Rostislav; Adeyanova, Irina; Kulakovskaya, Elena; Ostrovskaya, Lyudmila; Kvasha, Liliana; Cortina-Borja, Mario; Townsend, Claire L.

    2012-01-01

    Introduction HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe. Methods Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored. Results Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively). Conclusions In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV

  19. Travelling with HIV

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Parenting and HIV.

    Science.gov (United States)

    Rochat, Tamsen; Netsi, Elena; Redinger, Stephanie; Stein, Alan

    2017-06-01

    With the widespread use of antiretroviral therapy and successful prevention of mother-to-child transmission the development of HIV-negative children with HIV-positive parents has become an important focus. There is considerable evidence that children's developmental risk is heightened because a parental HIV-diagnosis is associated with a range of potential problems such as depression, stigma and financial difficulties. Up to a third of children in sub-Saharan Africa (SSA) are cared for by an HIV-positive parent or caregiver. We review the mechanisms by which HIV affects parenting including its negative effects on parental responsiveness in the early years of parenting and parental avoidant coping styles and parenting deficits in the later years. We describe low-cost parenting interventions suited for low resourced HIV endemic settings. Copyright © 2017. Published by Elsevier Ltd.

  1. HIV restriction by APOBEC3 in humanized mice.

    Directory of Open Access Journals (Sweden)

    John F Krisko

    2013-03-01

    Full Text Available Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3 family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV, Hepatitis B virus (HBV, Human Papilloma virus (HPV, and Human T Cell Leukemia virus (HTLV. The best characterized members of this family are APOBEC3G (A3G and APOBEC3F (A3F and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif. Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.

  2. Resin-Bonded Bridges in vitro and in vivo

    NARCIS (Netherlands)

    Veen, Johannes Hilbrandt van der

    1988-01-01

    In this thesis in vitro and in vivo studies on the clinical application of resin-bonded bridges are described and discussed. The development of different types of resin-bonded bridges is described in chapter 1. The bridges are often made by boding a cast metal retainer fitted with and artificial

  3. Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+ T cell responses in HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Núria Climent

    Full Text Available Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B in human monocyte-derived dendritic cells (MDDC and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α. MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

  4. HIV and Neurocognitive Dysfunction

    OpenAIRE

    Spudich, Serena

    2013-01-01

    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 ...

  5. Pregnancy and HIV infection

    OpenAIRE

    Mete Sucu; Cihan Cetin; Mehmet Ozsurmeli; Ghanim Khatib; Ceren Cetin; Cuneyt Evruke

    2016-01-01

    The management of Human Immunodeficiency Virus (HIV) infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinician...

  6. Paediatric HIV infection.

    Science.gov (United States)

    Scarlatti, G

    1996-09-28

    By the year 2000 there will be six million pregnant women and five to ten million children infected with HIV-1. Intervention strategies have been planned and in some instances already started. A timely and cost-effective strategy needs to take into account that most HIV-1 infected individuals reside in developing countries. Further studies are needed on immunological and virological factors affecting HIV-1 transmission from mother to child, on differential disease progression in affected children, and on transient infection.

  7. Transcriptome analysis of monocyte-HIV interactions

    Directory of Open Access Journals (Sweden)

    Tran Huyen

    2010-06-01

    macrophages can contribute to sustained chronic immune activation during HIV infection, e.g. through the perturbation of cytokine and chemokine networks 141516. With the acknowledged notion of chronic immune activation as a paradoxical driving force of immune suppression 17, this pro-inflammatory macrophage phenotype during HIV infection may be a crucial parameter in disease progression. Yet other macrophage dysfunctions are associated with more peripheral HIV- or ART-associated disorders such as atherosclerosis 18, lipodystrophy 19, and metabolic syndrome during HIV infection and/or combination ART 2021. Monocytes, for their part, are much less permissive to infection with HIV, both in vitro 22 and in vivo, where estimates of infected circulating monocytes are consistently low 2324. Circulating monocytes represent the most accessible primary model for macrophage dysfunction during HIV infection, however, and are furthermore of sufficient importance to study in their own right. Infectious virus can be recovered from circulating monocytes, both in untreated patients 24 and in patients undergoing long-term successful combination ART 25. Additionally, the circulating monocyte pool as a whole does seem to be affected during HIV infection, despite the low frequency of actually infected monocytes. Transcriptome studies, in particular, show a form of hybrid phenotype exhibiting both increased and decreased pro-inflammatory features 2627. This modulation of the non-infected monocyte population could be due to the virus itself through mechanisms which do not require direct infection 28, or to other factors contributing to (aberrant immune activation occurring during HIV infection, such as perturbed cytokine networks 29 or other inflammatory stimulants 30. Several key factors in the described dysregulated processes have been identified 1831, but many molecular components remain elusive. Furthermore, other aspects of HIV and combination ART pathogenesis in which monocyte

  8. 10 CFR 26.406 - Fitness monitoring.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Fitness monitoring. 26.406 Section 26.406 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.406 Fitness monitoring. (a...) Licensees and other entities shall implement a fitness monitoring program to deter substance abuse and...

  9. Benefit segmentation of the fitness market.

    Science.gov (United States)

    Brown, J D

    1992-01-01

    While considerate attention is being paid to the fitness and wellness needs of people by healthcare and related marketing organizations, little research attention has been directed to identifying the market segments for fitness based upon consumers' perceived benefits of fitness. This article describes three distinct segments of fitness consumers comprising an estimated 50 percent of households. Implications for marketing strategies are also presented.

  10. 14 CFR 31.43 - Fitting factor.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fitting factor. 31.43 Section 31.43... STANDARDS: MANNED FREE BALLOONS Design Construction § 31.43 Fitting factor. (a) A fitting factor of at least... structure. This factor applies to all parts of the fitting, the means of attachment, and the bearing on the...

  11. Family model of HIV care and treatment: a retrospective study in Kenya

    Science.gov (United States)

    2012-01-01

    Background Nyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV-infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal. Methods A family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV-positive members and to prevent new infections. Comprehensive family-centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach. Results Through the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV- positive partners among those tested: 71% and 89%, respectively. Conclusions The family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement. PMID:22353553

  12. Language and HIV communication

    Directory of Open Access Journals (Sweden)

    Lynn VA

    2017-09-01

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

  13. Fit to Electroweak Precision Data

    International Nuclear Information System (INIS)

    Erler, Jens

    2006-01-01

    A brief review of electroweak precision data from LEP, SLC, the Tevatron, and low energies is presented. The global fit to all data including the most recent results on the masses of the top quark and the W boson reinforces the preference for a relatively light Higgs boson. I will also give an outlook on future developments at the Tevatron Run II, CEBAF, the LHC, and the ILC

  14. Back school for fitness treinees

    OpenAIRE

    Líbalová, Kateřina

    2010-01-01

    In introductory chapters the work deals with theoretical starting points of exercising in fitness centres. It focuses on anatomical and physiological basis of exercises and neuromuscular imbalances which may be caused by inadequate exertion. In further chapters the work enlightens about the rudiments of sport training, training of strength and model form of a training unit. In final chapters suitable techniques of exercises of individual muscular systems are discussed. Common mistakes done by...

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

    Directory of Open Access Journals (Sweden)

    Ruizhong Shen

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

  16. HIV epidemics in Shenzhen and Chongqing, China.

    Directory of Open Access Journals (Sweden)

    Shu Yang

    Full Text Available Men who have sex with men (MSM and heterosexuals are the populations with the fastest growing HIV infection rates in China. We characterize the epidemic growth and age patterns between these two routes from 2004 to 2015 in Chongqing and Shenzhen, China.Data were downloaded from the National HIV/ AIDS Comprehensive Response Information Management System. For the new HIV diagnoses of heterosexuals and MSM in both cities, we estimated the growth rates by fitting different sub-exponential models. Heat maps are used to show their age patterns. We used histograms to compare these patterns by birth cohort.The MSM epidemics grew significantly in both cities. Chongqing experienced quadratic growth in HIV reported cases with an estimated growth rate of 0.086 per week and a "deceleration rate" of 0.673. HIV reported cases of MSM in Shenzhen grew even more drastically with a growth rate of 0.033 per week and "deceleration rate" of 0.794. The new infections are mainly affecting the ages of 18 to 30 in Chongqing and ages of 20 to 35 in Shenzhen. They peaked in early 1990's and mid-1990's birth cohorts in Chongqing and Shenzhen respectively. The HIV epidemic among heterosexuals grew rapidly in both cities. The growth rates were estimated as 0.02 and 0.028 in Chongqing and Shenzhen respectively whereas the "deceleration rates" were 0.878 and 0.790 in these two places. It affected mostly aged 18 to 75 in males and 18 to 65 in females in Chongqing and aged 18 to 45 in males and 18 to 50 in females in Shenzhen in 2015. In Chongqing, the heterosexual female epidemics display two peaks in HIV diagnoses in the birth cohorts of early 1950's and early 1980's, with heterosexual male epidemics peaked in early 1940's and early 1960's. The heterosexual male and female epidemics display higher rates in the birth cohort 1940-1960, than the birth cohort 1960-1990. It peaked in birth cohorts of 1950's and 1980's in Shenzhen.We revealed striking differences in epidemic growth

  17. Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

    Czech Academy of Sciences Publication Activity Database

    Weber, Jan; Gibson, R. M.; Sácká, Lenka; Strunin, Dmytro; Hodek, Jan; Weberová, Jitka; Pávová, Marcela; Alouani, D. J.; Asaad, R.; Rodriguez, B.; Lederman, M. M.; Quinones-Mateu, M. E.

    2017-01-01

    Roč. 14, Mar 20 (2017), č. článku 15. ISSN 1742-6405 R&D Projects: GA MŠk(CZ) LK11207 Institutional support: RVO:61388963 Keywords : HIV -1 * replicative fitness * disease progression * viremic non-progressors Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 1.605, year: 2016 https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0144-0

  18. AMS-02 fits dark matter

    Science.gov (United States)

    Balázs, Csaba; Li, Tong

    2016-05-01

    In this work we perform a comprehensive statistical analysis of the AMS-02 electron, positron fluxes and the antiproton-to-proton ratio in the context of a simplified dark matter model. We include known, standard astrophysical sources and a dark matter component in the cosmic ray injection spectra. To predict the AMS-02 observables we use propagation parameters extracted from observed fluxes of heavier nuclei and the low energy part of the AMS-02 data. We assume that the dark matter particle is a Majorana fermion coupling to third generation fermions via a spin-0 mediator, and annihilating to multiple channels at once. The simultaneous presence of various annihilation channels provides the dark matter model with additional flexibility, and this enables us to simultaneously fit all cosmic ray spectra using a simple particle physics model and coherent astrophysical assumptions. Our results indicate that AMS-02 observations are not only consistent with the dark matter hypothesis within the uncertainties, but adding a dark matter contribution improves the fit to the data. Assuming, however, that dark matter is solely responsible for this improvement of the fit, it is difficult to evade the latest CMB limits in this model.

  19. AMS-02 fits dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Balázs, Csaba; Li, Tong [ARC Centre of Excellence for Particle Physics at the Tera-scale,School of Physics and Astronomy, Monash University, Melbourne, Victoria 3800 (Australia)

    2016-05-05

    In this work we perform a comprehensive statistical analysis of the AMS-02 electron, positron fluxes and the antiproton-to-proton ratio in the context of a simplified dark matter model. We include known, standard astrophysical sources and a dark matter component in the cosmic ray injection spectra. To predict the AMS-02 observables we use propagation parameters extracted from observed fluxes of heavier nuclei and the low energy part of the AMS-02 data. We assume that the dark matter particle is a Majorana fermion coupling to third generation fermions via a spin-0 mediator, and annihilating to multiple channels at once. The simultaneous presence of various annihilation channels provides the dark matter model with additional flexibility, and this enables us to simultaneously fit all cosmic ray spectra using a simple particle physics model and coherent astrophysical assumptions. Our results indicate that AMS-02 observations are not only consistent with the dark matter hypothesis within the uncertainties, but adding a dark matter contribution improves the fit to the data. Assuming, however, that dark matter is solely responsible for this improvement of the fit, it is difficult to evade the latest CMB limits in this model.

  20. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  1. Clinical Management of HIV Drug Resistance

    Science.gov (United States)

    Cortez, Karoll J.; Maldarelli, Frank

    2011-01-01

    Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

  2. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    Science.gov (United States)

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  3. HIV-1 nef suppression by virally encoded microRNA

    Directory of Open Access Journals (Sweden)

    Brisibe Ebiamadon

    2004-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are 21~25-nucleotides (nt long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi, depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs inhibited the transcription of HIV-1. Results Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA that corresponded to a predicted nef miRNA (~25 nt, miR-N367 can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2. In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

  4. Retroviral DNA Integration Directed by HIV Integration Protein in Vitro

    Science.gov (United States)

    Bushman, Frederic D.; Fujiwara, Tamio; Craigie, Robert

    1990-09-01

    Efficient retroviral growth requires integration of a DNA copy of the viral RNA genome into a chromosome of the host. As a first step in analyzing the mechanism of integration of human immunodeficiency virus (HIV) DNA, a cell-free system was established that models the integration reaction. The in vitro system depends on the HIV integration (IN) protein, which was partially purified from insect cells engineered to express IN protein in large quantities. Integration was detected in a biological assay that scores the insertion of a linear DNA containing HIV terminal sequences into a λ DNA target. Some integration products generated in this assay contained five-base pair duplications of the target DNA at the recombination junctions, a characteristic of HIV integration in vivo; the remaining products contained aberrant junctional sequences that may have been produced in a variation of the normal reaction. These results indicate that HIV IN protein is the only viral protein required to insert model HIV DNA sequences into a target DNA in vitro.

  5. Emotional and Motivational Engagement at School Transition: A Qualitative Stage-Environment Fit Study

    Science.gov (United States)

    Symonds, Jennifer; Hargreaves, Linda

    2016-01-01

    Adolescents typically like school less after making age-graded school transitions. Stage-environment fit theory (Eccles & Midgley, 1989) attributes this to a mismatch between developmental needs and new school environments. Our in vivo study provides a basis for future quantitative designs by uncovering the most prevalent stage-environment…

  6. In vivo P-31 MR diffusion spectroscopy

    International Nuclear Information System (INIS)

    Moonen, C.T.W.; Vanzijl, P.C.M.; LeBihan, D.

    1988-01-01

    This paper discusses the Stejskal-Tanner diffusion spin-echo sequence modified for the in vivo diffusion spectroscopy. The apparent diffusion constant D α was measured as a function of the diffusion time. Contrary to the results in phantom samples, a strong dependency of the D α for phosphocreatine (PCr) in the rat muscle tissue on diffusion time was observed, clearly indicating restricted diffusion effects and allowing an approximation of the size of the restricted volume (8-13 μm). This size fits well with the known dimensions of a normal muscle cell

  7. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays

    NARCIS (Netherlands)

    Delwart, E. L.; Sheppard, H. W.; Walker, B. D.; Goudsmit, J.; Mullins, J. I.

    1994-01-01

    High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate

  8. Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.

    Directory of Open Access Journals (Sweden)

    Juanjuan Zhao

    2018-01-01

    Full Text Available Innate lymphoid cells (ILCs are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity. Highly active antiretroviral (HAART therapy in HIV-1 patients efficiently rescued the ILC1 numbers and reduced their activation, but failed to restore their functionality. We also found that blocking type-I interferon (IFN-I signaling during HIV-1 infection in vivo in humanized mice prevented HIV-1 induced depletion or apoptosis of ILC1 cells. Therefore, we have identified the CD4+ ILC1 cells as a new target population for HIV-1 infection, and revealed that IFN-I contributes to the depletion of ILC1s during HIV-1 infection.

  9. The Soldier Fitness Tracker: global delivery of Comprehensive Soldier Fitness.

    Science.gov (United States)

    Fravell, Mike; Nasser, Katherine; Cornum, Rhonda

    2011-01-01

    Carefully implemented technology strategies are vital to the success of large-scale initiatives such as the U.S. Army's Comprehensive Soldier Fitness (CSF) program. Achieving the U.S. Army's vision for CSF required a robust information technology platform that was scaled to millions of users and that leveraged the Internet to enable global reach. The platform needed to be agile, provide powerful real-time reporting, and have the capacity to quickly transform to meet emerging requirements. Existing organizational applications, such as "Single Sign-On," and authoritative data sources were exploited to the maximum extent possible. Development of the "Soldier Fitness Tracker" is the most recent, and possibly the best, demonstration of the potential benefits possible when existing organizational capabilities are married to new, innovative applications. Combining the capabilities of the extant applications with the newly developed applications expedited development, eliminated redundant data collection, resulted in the exceeding of program objectives, and produced a comfortable experience for the end user, all in less than six months. This is a model for future technology integration. (c) 2010 APA, all rights reserved.

  10. Where does fitness fit in theories of perception?

    Science.gov (United States)

    Anderson, Barton L

    2015-12-01

    Interface theory asserts that neither our perceptual experience of the world nor the scientific constructs used to describe the world are veridical. The primary argument used to uphold this claim is that (1) evolution is driven by a process of natural selection that favors fitness over veridicality, and (2) payoffs do not vary monotonically with truth. I argue that both the arguments used to bolster this claim and the conclusions derived from it are flawed. Interface theory assumes that perception evolved to directly track fitness but fails to consider the role of adaptation on ontogenetic time scales. I argue that the ubiquity of nonmonotonic payoff functions requires that (1) perception tracks "truth" for species that adapt on ontogenetic time scales and (2) that perception should be distinct from utility. These conditions are required to pursue an adaptive strategy to mitigate homeostatic imbalances. I also discuss issues with the interface metaphor, the particular formulation of veridicality that is considered, and the relationship of interface theory to the history of ideas on these topics.

  11. INFOS: spectrum fitting software for NMR analysis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Albert A., E-mail: alsi@nmr.phys.chem.ethz.ch [ETH Zürich, Physical Chemistry (Switzerland)

    2017-02-15

    Software for fitting of NMR spectra in MATLAB is presented. Spectra are fitted in the frequency domain, using Fourier transformed lineshapes, which are derived using the experimental acquisition and processing parameters. This yields more accurate fits compared to common fitting methods that use Lorentzian or Gaussian functions. Furthermore, a very time-efficient algorithm for calculating and fitting spectra has been developed. The software also performs initial peak picking, followed by subsequent fitting and refinement of the peak list, by iteratively adding and removing peaks to improve the overall fit. Estimation of error on fitting parameters is performed using a Monte-Carlo approach. Many fitting options allow the software to be flexible enough for a wide array of applications, while still being straightforward to set up with minimal user input.

  12. HIV-1 envelope glycoprotein

    Science.gov (United States)

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

    2017-08-22

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

  13. HIV and the eye

    African Journals Online (AJOL)

    In an area of high HIV prevalence, HIV-related ocular lesions are relatively common. L Visser, MB ... especially if this patient falls within the high- risk groups for ... Indications for treatment of ocular disease .... A lumbar puncture is needed to.

  14. Ludacris Talks About HIV

    Centers for Disease Control (CDC) Podcasts

    2012-07-24

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

  15. HIV and pregnancy

    OpenAIRE

    Lindgren, Susanne

    1996-01-01

    From the Department of Clinical Science, Divisions of Obstetrics and Gynaecology and Paediatrics and the Department of Immumology, Microbiology, Pathology and Infectious Diseases, Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden HIV and Pregnancy An Epidemiological, Clinical and Virological Study of HIV-infected Pregnant Women amd T...

  16. 4. CRIMINALISING HIV TRANSMISSION

    African Journals Online (AJOL)

    Esem

    A combination of effective evidence-based approaches should be adopted to expand ... global scenario, as well as its impact on the spread of new. HIV infections. .... in people not going for voluntary HIV testing for fear of being found positive ...

  17. HIV-associated vasculopathy

    African Journals Online (AJOL)

    Third World countries. HIV has brought an array of new clinical presentations and has also generated new syndromes.4. HIV vasculopathy was first described as an entity in 19875 and may ..... The EGF pathway is also implicated in cancer, which suggests that anticancer drugs that interfere with this pathway might increase.

  18. Psychogenic "HIV infection"

    NARCIS (Netherlands)

    Sno, H. N.; Storosum, J. G.; Wortel, C. H.

    1991-01-01

    The case of a man who falsely represented himself as being HIV positive is reported. In less than one year he was admitted twice with symptoms suggestive of HIV infection. The diagnoses malingering and factitious disorder were consecutively made. Early recognition of Factitious Disorder is essential

  19. HIV and AIDS

    Science.gov (United States)

    ... sex with infected partners. If a woman with HIV is pregnant, her newborn baby can catch the virus from ... from spreading to the baby. That's why all pregnant women should be tested for HIV so they can begin treatment if necessary. How ...

  20. HIV/AIDS - resources

    Science.gov (United States)

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

  1. Let's Stop HIV Together

    Centers for Disease Control (CDC) Podcasts

    2012-07-16

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

  2. HIV infection in Bophuthatswana

    African Journals Online (AJOL)

    ble exposure to HIV infection and associated risk fac- tors, information regarding demographic data, blood transfusion history, travelling from/to HIV endemic countries, history of imprisonment in the past 5 years, symptoms and signs of AIDS, lifestyle (number of sexu- al partners, heterosexual, homosexual, etc.) was collect-.

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

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

  5. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Science.gov (United States)

    Wang, Weimin; Cheng, Yan; Makarov, Edward; Ganesan, Murali; Gebhart, Catherine L.; Gorantla, Santhi; Osna, Natalia

    2018-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper. PMID:29361613

  6. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Directory of Open Access Journals (Sweden)

    Raghubendra Singh Dagur

    2018-02-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper.

  7. The FitTrack Index as fitness indicator: A pilot study | van Rensburg ...

    African Journals Online (AJOL)

    Conclusions: These results suggest that the web-based FitTrack Index may be considered an appropriate tool to evaluate exercise capacity and cardiovascular fitness in healthy individuals following an aerobic training programme. Keywords: Aerobic fitness, Exercise ability, Recreational fitness, Cardiovascular fitness, ...

  8. Nuclear fuel element end fitting

    International Nuclear Information System (INIS)

    Jabsen, F.S.

    1979-01-01

    A typical embodiment of the invention has an array of sockets that are welded to the intersections of the plates that form the upper and lower end fittings of a nuclear reactor fuel element. The sockets, which are generally cylindrical in shape, are oriented in directions that enable the longitudinal axes of the sockets to align with the longitudinal axes of the fuel rods that are received in the respective sockets. Detents impressed in the surfaces of the sockets engage mating grooves that are formed in the ends of the fuel rods to provide for the structural integrity of the fuel element

  9. HIV and mycobacteria.

    Science.gov (United States)

    Procop, Gary W

    2017-07-01

    The importance of mycobacteria as opportunistic pathogens, particularly members of the M. avium complex (MAC), in patients with progressive HIV infection was recognized early in the AIDS epidemic. It took longer to appreciate the global impact and devastation that would result from the deadly synergy that exists between HIV and M. tuberculosis. This HIV/M. tuberculosis co-pandemic is ongoing and claiming millions of lives every year. In addition to MAC, a number of other non-tuberculous mycobacteria have been recognized as opportunistic pathogens in HIV-infected individuals; some of these are more commonly encountered (e.g., M. kansasii) than others (M. haemophilum and M. genevense). Finally, there are challenges to concomitantly treating the HIV and the infecting Mycobacterium species, because of antimicrobial resistance, therapeutic side-effects and the complex pharmacologic interactions of the antiretroviral and antimycobacterial multidrug therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. HIV and travel.

    Science.gov (United States)

    Schuhwerk, M A; Richens, J; Zuckerman, Jane N

    2006-01-01

    There is a high demand for travel among HIV-positive individual. This demand arises partly from those who have benefited from advances in antiretroviral therapy as well as those with disease progression. The key to a successful and uneventful holiday lies in careful pre-trip planning, yet many patients fail to obtain advice before travelling. Travel advice for HIV patients is becoming increasingly specialized. In addition to advice on common travel-related infectious diseases, HIV-positive travellers are strongly advised to carry information with them and they need specific advice regarding country entry restrictions, HIV inclusive travel insurance, safety of travel vaccinations and highly active antiretroviral therapy-related issues. A wide range of relevant issues for the HIV-positive traveller are discussed in this review and useful websites can be found at the end.

  11. HIV and chronic kidney disease

    OpenAIRE

    Naicker, Saraladevi; Rahmania, Sadaf; Kopp, Jeffrey B.

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 – 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune comple...

  12. Indikatorsygdomme for hiv-infektion

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  13. The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity

    Directory of Open Access Journals (Sweden)

    Natalie M. Zahr

    2018-03-01

    Full Text Available As successfully treated individuals with Human Immunodeficiency Virus (HIV-infected age, cognitive and health challenges of normal aging ensue, burdened by HIV, treatment side effects, and high prevalence comorbidities, notably, Alcohol Use Disorders (AUD and Hepatitis C virus (HCV infection. In 2013, people over 55 years old accounted for 26% of the estimated number of people living with HIV (~1.2 million. The aging brain is increasingly vulnerable to endogenous and exogenous insult which, coupled with HIV infection and comorbid risk factors, can lead to additive or synergistic effects on cognitive and motor function. This paper reviews the literature on neuropsychological and in vivo Magnetic Resonance Imaging (MRI evaluation of the aging HIV brain, while also considering the effects of comorbidity for AUD and HCV.

  14. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  15. Physics of HIV

    Science.gov (United States)

    Tristram-Nagle, Stephanie

    2018-05-01

    This review summarizes over a decade of investigations into how membrane-binding proteins from the HIV-1 virus interact with lipid membrane mimics of various HIV and host T-cell membranes. The goal of the work was to characterize at the molecular level both the elastic and structural changes that occur due to HIV protein/membrane interactions, which could lead to new drugs to thwart the HIV virus. The main technique used to study these interactions is diffuse x-ray scattering, which yields the bending modulus, K C, as well as structural parameters such as membrane thickness, area/lipid and position of HIV peptides (parts of HIV proteins) in the membrane. Our methods also yield information about lipid chain order or disorder caused by the peptides. This review focuses on three stages of the HIV-1 life cycle: (1) infection, (2) Tat membrane transport, and (3) budding. In the infection stage, our lab studied three different parts of HIV-1 gp41 (glycoprotein 41 fusion protein): (1) FP23, the N-terminal 23 amino acids that interact non-specifically with the T-cell host membrane to cause fusion of two membranes, and its trimer version, (2) cholesterol recognition amino acid consensus sequence, on the membrane proximal external region near the membrane-spanning domain, and (3) lentiviral lytic peptide 2 on the cytoplasmic C-terminal tail. For Tat transport, we used membrane mimics of the T-cell nuclear membrane as well as simpler models that varied charge and negative curvature. For membrane budding, we varied the myristoylation of the MA31 peptide as well as the negatively charged lipid. These studies show that HIV peptides with different roles in the HIV life cycle affect differently the relevant membrane mimics. In addition, the membrane lipid composition plays an important role in the peptides’ effects.

  16. Construction and fitting of NUCEF

    International Nuclear Information System (INIS)

    Takeshita, Isao; Itahashi, Takayuki; Izawa, Naoki; Okazaki, Shuji

    1994-01-01

    NUCEF consists of two criticality experiment devices, three alpha-gamma cells, the experimental equipments contained in about 90 glove boxes and many others. The background and the course of the construction and fitting of NUCEF are described on the selection of important research, the rationalization of facilities, the integration of the criticality safety experiments facility(CSEF) and the TRU safety test facility(TRUST), the safety examination, and the construction and fitting. The whole NUCEF, the static criticality facility(STACY), the transient criticality facility(TRACY), the mock-up test of the machinery and equipment for both criticality facilities, the solution fuel preparation facility, cells and glove boxes and the equipment contained in them, the analysis facility consists of four analysis rooms, and the radioactive waste facility for gas, liquid and solid wastes are described. The classification of these facilities based on the relevant laws is shown. The way of thinking in the basic design and the detailed design is explained. The permission of nuclear reactor installation and the use of nuclear fuel substances was obtained. The design and the method of works were approved. The inspection is reported. The measures for the security are explained. (K.I.)

  17. Whole Protein Native Fitness Potentials

    Science.gov (United States)

    Faraggi, Eshel; Kloczkowski, Andrzej

    2013-03-01

    Protein structure prediction can be separated into two tasks: sample the configuration space of the protein chain, and assign a fitness between these hypothetical models and the native structure of the protein. One of the more promising developments in this area is that of knowledge based energy functions. However, standard approaches using pair-wise interactions have shown shortcomings demonstrated by the superiority of multi-body-potentials. These shortcomings are due to residue pair-wise interaction being dependent on other residues along the chain. We developed a method that uses whole protein information filtered through machine learners to score protein models based on their likeness to native structures. For all models we calculated parameters associated with the distance to the solvent and with distances between residues. These parameters, in addition to energy estimates obtained by using a four-body-potential, DFIRE, and RWPlus were used as training for machine learners to predict the fitness of the models. Testing on CASP 9 targets showed that our method is superior to DFIRE, RWPlus, and the four-body potential, which are considered standards in the field.

  18. Surfactant Protein D modulates HIV infection of both T-cells and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Jens Madsen

    Full Text Available Surfactant Protein D (SP-D is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo.

  19. Nano-Medicine as a Newly Emerging Approach to Combat Human Immunodeficiency Virus (HIV).

    Science.gov (United States)

    Saravanan, Muthupandian; Asmalash, Tsehaye; Gebrekidan, Atsebaha; Gebreegziabiher, Dawit; Araya, Tadele; Hilekiros, Haftamu; Barabadi, Hamed; Ramanathan, Kumaresan

    2018-01-01

    Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers. The present study aimed to review the recent progress in nanomedicine as a newly emerging approach to combat HIV. The scientific data bases reviewed carefully to find both in vitro and in vivo studies representing the role of nonomedicine to combat HIV. Impressively, nanomedicine drug delivery systems have been commendable in various models ranging from in vitro to in vivo. It gives notion about the application of nano-carrier systems for the delivery of anti-retroviral drugs which ideally should provide better distribution to surpass Blood- Brain Barrier (BBB) and other tissue or to overcome innate barriers such as mucus. Considerably, nanomaterials such as dendrimers and many other inorganic NPs such as silver, gold, iron, and zinc can be used for HIV treatment by interfering in varying stages of HIV life cycle. Furthermore, NPs could best act as adjuvants, convoys during vaccine delivery, as intra-vaginal microbicides and for the early detection of HIV-1 p24 antigen. Nanomedicine may be a proper approach in HIV/AIDS therapy by means of offering lower dosage and side effect, better patient-to-patient consistency, bioavailability, target specificity and improved sensitivity of HIV diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Desmosomes In Vivo

    Directory of Open Access Journals (Sweden)

    David Garrod

    2010-01-01

    Full Text Available The structure, function, and regulation of desmosomal adhesion in vivo are discussed. Most desmosomes in tissues exhibit calcium-independent adhesion, which is strongly adhesive or “hyperadhesive”. This is fundamental to tissue strength. Almost all studies in culture are done on weakly adhesive, calcium-dependent desmosomes, although hyperadhesion can be readily obtained in confluent cell culture. Calcium dependence is a default condition in vivo, found in wounds and embryonic development. Hyperadhesion appears to be associated with an ordered arrangement of the extracellular domains of the desmosomal cadherins, which gives rise to the intercellular midline identified in ultrastructural studies. This in turn probably depends on molecular order in the desmosomal plaque. Protein kinase C downregulates hyperadhesion and there is preliminary evidence that it may also be regulated by tyrosine kinases. Downregulation of desmosomes in vivo may occur by internalisation of whole desmosomes rather than disassembly. Hyperadhesion has implications for diseases such as pemphigus.

  1. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

    Science.gov (United States)

    Ladinsky, Mark S; Kieffer, Collin; Olson, Gregory; Deruaz, Maud; Vrbanac, Vladimir; Tager, Andrew M; Kwon, Douglas S; Bjorkman, Pamela J

    2014-01-01

    Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of

  2. Electron tomography of HIV-1 infection in gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Mark S Ladinsky

    2014-01-01

    Full Text Available Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET to image HIV-1 in gut-associated lymphoid tissue (GALT of HIV-1-infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1-infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural

  3. Psychometric evaluation of the HIV symptom distress scale

    Science.gov (United States)

    Marc, Linda G.; Wang, Ming-Mei; Testa, Marcia A.

    2012-01-01

    The objective of this paper is to psychometrically validate the HIV Symptom Distress Scale (SDS), an instrument that can be used to measure overall HIV symptom distress or clinically relevant groups of HIV symptoms. A secondary data analysis was conducted using the Collaborations in HIV Outcomes Research U.S. Cohort (CHORUS). Inclusion criteria required study participants (N=5,521) to have a valid baseline measure of the AIDS Clinical Trial Group Symptom Distress Module, with an SF-12 or SF-36 completed on the same day. Psychometric testing assessed unidimensionality, internal consistency and factor structure using exploratory and confirmatory factor analysis, and structural equation modeling (SEM). Construct validity examined whether the new measure discriminates across clinical significance (CD4 and HIV viral load). Findings show that the SDS has high reliability (α=0.92), and SEM supports a correlated second-order factor model (physical and mental distress) with acceptable fit (GFI=0.88, AGFI=0.85, NFI=0.99, NNFI=0.99; RMSEA=0.06, [90% CI 0.06 – 0.06]; Satorra Bentler Scaled, C2 =3274.20; p=0.0). Construct validity shows significant differences across categories for HIV-1 viral load (p< 0.001) and CD4 (p< 0.001). Differences in mean SDS scores exist across gender (p< 0.001), race/ethnicity (p< 0.05) and educational attainment (p < 0.001). Hence, the HIV Symptom Distress Scale is a reliable and valid instrument, which measures overall HIV symptoms or clinically relevant groups of symptoms. PMID:22409246

  4. Alternative Forms of Fit in Contingency Theory.

    Science.gov (United States)

    Drazin, Robert; Van de Ven, Andrew H.

    1985-01-01

    This paper examines the selection, interaction, and systems approaches to fit in structural contingency theory. The concepts of fit evaluated may be applied not only to structural contingency theory but to contingency theories in general. (MD)

  5. Cardiorespiratory Fitness Profile of Undergraduate Biomedical ...

    African Journals Online (AJOL)

    ... for developing sedentary habits, which could lead to reduced cardiorespiratory fitness. ... This study therefore examined the cardiorespiratory fitness (CRF) profile of ... A modified sub-maximal cycle ergometer protocol was used to estimate ...

  6. Mapping organizational members' sense of fit

    OpenAIRE

    Billsberry, Jon; Marsh, Philip; Moss-Jones, John

    2004-01-01

    Despite its importance in the organizational behavior literature, person–organization (P–O) fit remains an elusive construct. One reason for this is the lack of research about organizational members’ own sense of their P–O fit. In this paper we report an empirical study that explored organizational members’ own sense of fit using storytelling and causal mapping techniques. The results suggest that organizational members categorize their perceptions of their fit into five discrete domains (job...

  7. Addressing men and gender diversity in education: a promising solution to the HIV/AIDS epidemic.

    Science.gov (United States)

    Ghajarieh, Amir Biglar Beigi; Kow, Karen Yip Cheng

    2011-04-01

    To date, researchers investigating gender in relation to social issues underscore women and appear to sideline men. Focusing on women in studies concerning sociogender issues may exclude not only men from mainstream research, but also those who do not fit into the binary gender system, including gay, lesbian, bisexual, and transgender (GLBT) people. One area closely related to gender issues is the HIV epidemic. Mainstream discussions of men and other versions of masculinity and femininity including GLBT people in the gender-related studies of the HIV epidemic can decrease the vulnerability of individuals against HIV infections regardless of their biological sex.

  8. HIV/AIDS Clinical Trials Fact Sheet

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Overview Home Understanding HIV/AIDS Fact Sheets HIV/ ... 4 p.m. ET) Send us an email HIV/AIDS Clinical Trials Last Reviewed: August 25, 2017 ...

  9. What is a Preventive HIV Vaccine?

    Science.gov (United States)

    ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ...

  10. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon

    Science.gov (United States)

    Akiyama, Hisashi; Ramirez, Nora-Guadalupe Pina; Gibson, Gregory; Kline, Christopher; Watkins, Simon; Ambrose, Zandrea

    2017-01-01

    ABSTRACT A hallmark of human immunodeficiency virus type 1 (HIV-1) infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+ T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4+ T cells in trans and thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activation in vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gag and CD169, suggesting productive infection of CD169+ myeloid cells in vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+ T cells was robustly decreased, initiation of infection in trans via coculture with CD169+ IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 in cis and in trans to attenuate a type I IFN-induced antiviral state. IMPORTANCE HIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN

  11. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-03

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

  12. 48 CFR 752.7033 - Physical fitness.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Physical fitness. 752.7033 Section 752.7033 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CLAUSES AND... fitness. For use in all USAID contracts involving performance overseas. Physical Fitness (JUL 1997) (The...

  13. Having a Ball with Fitness Balls

    Science.gov (United States)

    McNulty, Betty

    2011-01-01

    Fitness programs can be greatly enhanced with the addition of fitness balls. They are a fun, challenging, economical, and safe way to incorporate a cardiovascular, strength, and stretching program for all fitness levels in a physical education setting. The use of these balls has become more popular during the last decade, and their benefits and…

  14. HRM and Fit: Survival of the fittest!?

    NARCIS (Netherlands)

    C.T. Boon (Corine)

    2008-01-01

    textabstractWhat is the nature of ‘fit’ in strategic HRM? This is the question guiding this thesis. Although the idea of fit is theoretically convincing, empirical evidence to support the role of fit is limited. Previous studies on fit have mainly focused on the alignment between HRM and strategy

  15. The simplest formal argument for fitness optimization

    Indian Academy of Sciences (India)

    The Formal Darwinism Project aims to provide a formal argument linking population genetics to fitness optimization, which of necessity includes defining fitness. This bridges the gulf between those biologists who assume that natural selection leads to something close to fitness optimization and those biologists who believe ...

  16. Relationship among Fitness, Morphological Characteristics, Skills ...

    African Journals Online (AJOL)

    The specific morphological and fitness demands of the sport are, therefore, not fully understood. The purpose of this ... The findings convincingly suggest that coaches should include fitness, morphological and skills tests in their coaching and fitness programmes, team selection and talent identification processes. Keywords: ...

  17. Exercise, fitness, and the gut.

    Science.gov (United States)

    Cronin, Owen; Molloy, Michael G; Shanahan, Fergus

    2016-03-01

    Exercise and gut symptomatology have long been connected. The possibility that regular exercise fosters intestinal health and function has been somewhat overlooked in the scientific literature. In this review, we summarize current knowledge and discuss a selection of recent, relevant, and innovative studies, hypotheses and reviews that elucidate a complex topic. The multiorgan benefits of regular exercise are extensive. When taken in moderation, these benefits transcend improved cardio-respiratory fitness and likely reach the gut in a metabolic, immunological, neural, and microbial manner. This is applicable in both health and disease. However, further work is required to provide safe, effective recommendations on physical activity in specific gastrointestinal conditions. Challenging methodology investigating the relationship between exercise and gut health should not deter from exploring exercise in the promotion of gastrointestinal health.

  18. Becoming fit for transnational comparability

    DEFF Research Database (Denmark)

    Krejsler, John Benedicto; Ulf, Olsson; Kenneth, Petersson

    2018-01-01

    . Consequently, Danish teacher education discourse has emerged from a distinctly national vocational seminary tradition, into a modernized university college discourse that increasingly fits the transnational templates of comparability, albeit at a slower pace than her Swedish neighbor. It is often difficult...... of modern nations, if they are to succeed in “an increasingly competitive global race among knowledge economies.” In the case of the Bologna Process, the transformative effects are often rather direct. More often, however, effects touch upon national educational agendas in indirect ways, in terms......This chapter traces how national teacher education policy discourse in Denmark and Sweden is being transformed by opaque, albeit often inclusive, processes in transnational policy forums, such as the Bologna Process, OECD, and EU. This is facilitated by “soft law” surrounding the imagined needs...

  19. Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

    International Nuclear Information System (INIS)

    Ganusov, Vitaly V; Neher, Richard A; Perelson, Alan S

    2013-01-01

    Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2–3 weeks postinfection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4–12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Indeed, the viral population ‘escapes’ from about half of the CTL responses by mutation in the first year. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the model fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with

  20. HIV counselling in prisons.

    Science.gov (United States)

    Curran, L; McHugh, M; Nooney, K

    1989-01-01

    HIV presents particular problem in penal establishments: the nature of the population; conditions in prison; media attention and misinformation; the possibility of transmission within and beyond the prison population; the extra issues that apply to female prisoners. These are discussed in the context of prison policy regarding HIV and the broad strategic approach which is being adopted to manage the problem of HIV within penal institutions. Counselling has a key role in the overall strategy. Pre- and post-test counselling with prisoners is described and the particular problems presented by inmates are discussed and illustrated by reference to case histories. Developments in counselling provision for inmates are outlined.

  1. Benchmarking HIV health care

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Reekie, Joanne; Mocroft, Amanda

    2012-01-01

    ABSTRACT: BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV-patients based on four key indicators. METHODS: Four indicators of health care we...... document pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for assessment and benchmarking the clinical management of HIV-patients in any setting worldwide....

  2. Nutrition and HIV

    DEFF Research Database (Denmark)

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

    2017-01-01

    , which is mainly synergistic and operating at different levels. HIV infection increases energy and nutrient requirements, yet it reduces food security. The result is nutritional deficiencies, which increase progression of HIV infection. Both undernutrition and food insecurity may also lead to increased...... risk of transmission. Nutritional intake and status may affect metabolism of antiretroviral drugs, some of which may affect body composition, and increase risk of the metabolic syndrome. In addition, HIV is transmitted through breastfeeding, causing a serious infant feeding dilemma for which...

  3. HIV in Pregnancy.

    Science.gov (United States)

    Roth, Cheryl; Hrenchir, Pauline F; Pacheco, Christine J

    2016-01-01

    In the United States, women with HIV have the ability to make informed choices relating to their reproductive lives more now than ever before. The increasing availability of antiretroviral therapy has spurred renewed interest among many HIV-positive women in their decisions about whether to have children. It is important for perinatal nurses to understand the maternal and fetal implications of HIV in pregnancy, including parameters for treatment and the drug regimens typically used during the antepartum, intrapartum, and postpartum periods. © 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  4. In vitro HIV-1 evolution in response to triple reverse transcriptase inhibitors & in silico phenotypic analysis.

    Directory of Open Access Journals (Sweden)

    Barbara A Rath

    Full Text Available Effectiveness of ART regimens strongly depends upon complex interactions between the selective pressure of drugs and the evolution of mutations that allow or restrict drug resistance.Four clinical isolates from NRTI-exposed, NNRTI-naive subjects were passaged in increasing concentrations of NVP in combination with 1 µM 3 TC and 2 µM ADV to assess selective pressures of multi-drug treatment. A novel parameter inference procedure, based on a stochastic viral growth model, was used to estimate phenotypic resistance and fitness from in vitro combination passage experiments.Newly developed mathematical methods estimated key phenotypic parameters of mutations arising through selective pressure exerted by 3 TC and NVP. Concentrations of 1 µM 3 TC maintained the M184V mutation, which was associated with intrinsic fitness deficits. Increasing NVP concentrations selected major NNRTI resistance mutations. The evolutionary pathway of NVP resistance was highly dependent on the viral genetic background, epistasis as well as stochasticity. Parameter estimation indicated that the previously unrecognized mutation L228Q was associated with NVP resistance in some isolates.Serial passage of viruses in the presence of multiple drugs may resemble the selection of mutations observed among treated individuals and populations in vivo and indicate evolutionary preferences and restrictions. Phenotypic resistance estimated here "in silico" from in vitro passage experiments agreed well with previous knowledge, suggesting that the unique combination of "wet-" and "dry-lab" experimentation may improve our understanding of HIV-1 resistance evolution in the future.

  5. Regression models for interval censored survival data: Application to HIV infection in Danish homosexual men

    DEFF Research Database (Denmark)

    Carstensen, Bendix

    1996-01-01

    This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men.......This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men....

  6. Neurological complication in HIV patients

    Science.gov (United States)

    Ritarwan, K.

    2018-03-01

    Human Immunodeficiency Virus (HIV) is neurotropic and immunotropic, making themassive destruction of both systems. Although their amount has been reduced, there is still neurological presentations and complications of HIV remain common in the era of combination antiretroviral therapy (cART). Neurological opportunistic infections (OI) occur in advanced HIV diseases such as primary cerebral lymphoma, cryptococcal meningitis, cerebral toxoplasmosis, and progressive multifocal encephalopathy. Neurological problem directly related to HIV appear at any stage in the progress of HIV disease, from AIDS-associated dementia to the aseptic meningitis of primary HIV infection observed in subjects with an immune deficiency. The replication of peripheral HIV viral is able to be controlled in the era of effective antiretroviral therapy. Non-HIV-related neurological disease such as stroke increased important as the HIV population ages.

  7. Decoding noises in HIV computational genotyping.

    Science.gov (United States)

    Jia, MingRui; Shaw, Timothy; Zhang, Xing; Liu, Dong; Shen, Ye; Ezeamama, Amara E; Yang, Chunfu; Zhang, Ming

    2017-11-01

    Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  9. HIV-1 protease-substrate coevolution in nelfinavir resistance.

    Science.gov (United States)

    Kolli, Madhavi; Ozen, Ayşegül; Kurt-Yilmaz, Nese; Schiffer, Celia A

    2014-07-01

    Resistance to various human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. The virus accumulates mutations within the protease (PR) that render the PIs less potent. Occasionally, Gag sequences also coevolve with mutations at PR cleavage sites contributing to drug resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. This interdependency in the PR-p1-p6 interactions enhances intermolecular contacts and reinforces the overall fit of the substrate within the substrate envelope, likely enabling coevolution to sustain substrate recognition and cleavage in the presence of PR resistance mutations. Resistance to human immunodeficiency virus type 1 (HIV-1) protease inhibitors challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. Mutations in HIV-1 protease selected under the pressure of protease inhibitors render the inhibitors less potent. Occasionally, Gag sequences also mutate and coevolve with protease, contributing to maintenance of viral fitness and to drug resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. Our structural analysis reveals the interdependency of protease-substrate interactions and how coevolution may restore substrate recognition and cleavage in the presence of protease drug resistance mutations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

    International Nuclear Information System (INIS)

    Kusano, Shuichi; Eizuru, Yoshito

    2013-01-01

    Highlights: •PLSCR1 specifically interacted with HIV-1 Tat in vitro and in vivo. •PLSCR1 repressed Tat-dependent transactivation of the HIV-1 LTR. •Suppression of PLSCR1 expression enhanced the levels of HIV-1 transcripts. •PLSCR1 reduced the nuclear localization of Tat. -- Abstract: Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160–250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection

  11. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina

    Directory of Open Access Journals (Sweden)

    Xiao-Liang ZHANG

    2016-07-01

    Full Text Available Northern pig-tailed macaques (NPMs, Macaca leonina are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.

  12. New ROOT Graphical User Interfaces for fitting

    International Nuclear Information System (INIS)

    Maline, D Gonzalez; Moneta, L; Antcheva, I

    2010-01-01

    ROOT, as a scientific data analysis framework, provides extensive capabilities via Graphical User Interfaces (GUI) for performing interactive analysis and visualizing data objects like histograms and graphs. A new interface for fitting has been developed for performing, exploring and comparing fits on data point sets such as histograms, multi-dimensional graphs or trees. With this new interface, users can build interactively the fit model function, set parameter values and constraints and select fit and minimization methods with their options. Functionality for visualizing the fit results is as well provided, with the possibility of drawing residuals or confidence intervals. Furthermore, the new fit panel reacts as a standalone application and it does not prevent users from interacting with other windows. We will describe in great detail the functionality of this user interface, covering as well new capabilities provided by the new fitting and minimization tools introduced recently in the ROOT framework.

  13. Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality.

    Directory of Open Access Journals (Sweden)

    David Beauparlant

    2017-03-01

    Full Text Available A hallmark of HIV-1 infection is the continuously declining number of the virus' predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to CD4low targets proved to severely alter envelope functions including trimer opening as indicated by a higher affinity to CD4 and loss in shielding against neutralizing antibodies. We observed a strikingly decreased infectivity on CD4high target cells, but sustained infectivity on CD4low targets, including macrophages. Intriguingly, the adaptation to CD4low targets altered the kinetic of the entry process, leading to rapid CD4 engagement and an extended transition time between CD4 and CCR5 binding during entry. This phenotype was also observed for certain central nervous system (CNS derived macrophage-tropic viruses, highlighting that the functional perturbation we defined upon in vitro adaptation to CD4low targets occurs in vivo. Collectively, our findings suggest that CD4low adapted envelopes may exhibit severe deficiencies in entry fitness and shielding early in their evolution. Considering this, adaptation to CD4low targets may preferentially occur in a sheltered and immune-privileged environment such as the CNS to allow fitness restoring compensatory mutations to occur.

  14. Mouth Problems and HIV

    Science.gov (United States)

    ... teeth (periodontitis), canker sores, oral warts, fever blisters, oral candidiasis (thrush), hairy leukoplakia (which causes a rough, white patch on the tongue), and dental caries. Read More Publications Cover image Mouth Problems + HIV Publication files Download Language English PDF — ...

  15. HIV/AIDS

    Science.gov (United States)

    ... first signs of HIV infection Diarrhea Weight loss Oral yeast infection (thrush) Shingles (herpes zoster) Progression to AIDS Thanks ... eyes, digestive tract, lungs or other organs. Candidiasis. Candidiasis ... tongue, esophagus or vagina. Cryptococcal meningitis. Meningitis is ...

  16. Pregnancy and HIV infection

    Directory of Open Access Journals (Sweden)

    Mete Sucu

    2016-12-01

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

  17. HIV status and tuberculosis

    African Journals Online (AJOL)

    User

    Failure to perform mycobacterium culture bacterial blood culture and results of other causes of .... for Identification of Highly Infectious Tuberculosis in People Living with HIV in Southeast Asia. ... Indian Journal of Tuberculosis 58, 108-112.

  18. How Is HIV Transmitted?

    Science.gov (United States)

    ... used needle up to 42 days depending on temperature and other factors. Less commonly, HIV may be ... December 1 World AIDS Day Event Planning Guide Learning Opportunities Learning Opportunities Want to stay abreast of ...

  19. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... Disorders Fibromyalgia Food and Waterborne Illness Fungal Infections Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart ... antiretroviral therapy (ART) drugs. The test analyzes the genes of the HIV strain infecting the person to ...

  20. Primaer HIV-infektion

    DEFF Research Database (Denmark)

    Pedersen, C; Pedersen, B K

    1996-01-01

    Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely...

  1. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-05

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

  2. Curaxin CBL0100 Blocks HIV-1 Replication and Reactivation through Inhibition of Viral Transcriptional Elongation

    Directory of Open Access Journals (Sweden)

    Maxime J. Jean

    2017-10-01

    Full Text Available Despite combination antiretroviral therapy (cART, acquired immunodeficiency syndrome (AIDS, predominantly caused by the human immunodeficiency virus type 1 (HIV-1, remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the “shock and kill” strategy using latency-reversing agents (LRAs to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges. Recently, the “block and lock” strategy has been proposed. It aims to reinforce a deep state of latency and prevent sporadic reactivation (“blip” of HIV-1 using latency-promoting agents (LPAs for a functional cure. Our studies of curaxin 100 (CBL0100, a small-molecule targeting the facilitates chromatin transcription (FACT complex, show that it blocks both HIV-1 replication and reactivation in in vitro and ex vivo models of HIV-1. Mechanistic investigation elucidated that CBL0100 preferentially targets HIV-1 transcriptional elongation and decreases the occupancy of RNA Polymerase II (Pol II and FACT at the HIV-1 promoter region. In conclusion, CBL0100 is a newly identified inhibitor of HIV-1 transcription that can be used as an LPA in the “block and lock” cure strategy.

  3. Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection.

    Science.gov (United States)

    Cohen, Yehuda Z; Caskey, Marina

    2018-04-24

    Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency that target different HIV-1 envelope epitopes have been identified. bNAbs are an attractive new strategy for HIV-1 prevention and therapy, and potentially, for long-term remission or cure. Here, we discuss findings from early clinical studies that have evaluated these novel bNAbs. Phase 1 studies of bNAbs targeting two distinct HIV-1 envelope epitopes have demonstrated their favorable safety and pharmacokinetic profile. Single bNAb infusions led to significant, but transient, decline in viremia with selection of escape variants. A single bNAb also delayed viral rebound in ART-treated participants who discontinued ART. Importantly, in-vivo efficacy was related to antibody potency and to the level of preexisting resistance. Studies in animal models showed that bNAbs can clear HIV-infected cells and modulate host immune responses. These findings suggest that bNAbs may target the latent HIV reservoir in humans and could contribute to long-term remission of HIV-1 infection. bNAbs may offer advantages over traditional ART for both the prevention and treatment of HIV-1 infection. In addition, bNAbs may target the latent viral reservoir. bNAb combinations and bNAbs engineered for prolonged half-life and increased potency are currently undergoing clinical evaluation.

  4. Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

    Science.gov (United States)

    Carias, Ann M.; McCoombe, Scott; McRaven, Michael; Anderson, Meegan; Galloway, Nicole; Vandergrift, Nathan; Fought, Angela J.; Lurain, John; Duplantis, Maurice; Veazey, Ronald S.

    2013-01-01

    Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4+ target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection. PMID:23966398

  5. Antimalarial activity of HIV-1 protease inhibitor in chromone series.

    Science.gov (United States)

    Lerdsirisuk, Pradith; Maicheen, Chirattikan; Ungwitayatorn, Jiraporn

    2014-12-01

    Increasing parasite resistance to nearly all available antimalarial drugs becomes a serious problem to human health and necessitates the need to continue the search for new effective drugs. Recent studies have shown that clinically utilized HIV-1 protease (HIV-1 PR) inhibitors can inhibit the in vitro and in vivo growth of Plasmodium falciparum. In this study, a series of chromone derivatives possessing HIV-1 PR inhibitory activity has been tested for antimalarial activity against P. falciparum (K1 multi-drug resistant strain). Chromone 15, the potent HIV-1 PR inhibitor (IC50=0.65μM), was found to be the most potent antimalarial compound with IC50=0.95μM while primaquine and tafenoquine showed IC50=2.41 and 1.95μM, respectively. Molecular docking study of chromone compounds against plasmepsin II, an aspartic protease enzyme important in hemoglobin degradation, revealed that chromone 15 exhibited the higher binding affinity (binding energy=-13.24kcal/mol) than the known PM II inhibitors. Thus, HIV-1 PR inhibitor in chromone series has the potential to be a new class of antimalarial agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus

    Science.gov (United States)

    Kell, Alison M.; Wargo, Andrew R.; Kurath, Gael

    2014-01-01

    Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution.

  7. The in vitro fitness cost of antimicrobial resistance in Escherichia coli varies with the growth conditions

    DEFF Research Database (Denmark)

    Petersen, Andreas; Aarestrup, Frank Møller; Olsen, John Elmerdahl

    2009-01-01

    The objective of this study was to investigate the influence of stressful growth conditions on the fitness cost of antimicrobial resistance in Escherichia coli BJ4 caused by chromosomal mutations and plasmid acquisition. The fitness cost of chromosomal streptomycin resistance increased......H and at high-salt concentrations. Strains with an impaired rpoS demonstrated a reduced fitness only during growth in a high-salt concentration. In conclusion, it was demonstrated that bacterial fitness cost in association with antimicrobial resistance generally increases under stressful growth conditions....... However, the growth potential of bacteria with antimicrobial resistances did not increase in a straightforward manner in these in vitro experiments and is therefore probably even more difficult to predict in vivo....

  8. HIV and bone disease.

    Science.gov (United States)

    Stone, Benjamin; Dockrell, David; Bowman, Christine; McCloskey, Eugene

    2010-11-01

    Advances in management have resulted in a dramatic decline in mortality for individuals infected with human immunodeficiency virus (HIV). This decrease in mortality, initially the result of improved prophylaxis and treatment of opportunistic infections but later mediated by the use of highly-active antiretroviral therapy (HAART) has led to the need to consider long-term complications of the disease itself, or its treatment. Bone disease is increasingly recognised as a concern. The prevalence of reduced BMD and possibly also fracture incidence are increased in HIV-positive individuals compared with HIV-negative controls. There are many potential explanations for this - an increased prevalence of established osteoporosis risk factors in the HIV-positive population, a likely direct effect of HIV infection itself and a possible contributory role of ARV therapy. At present, the assessment of bone disease and fracture risk remains patchy, with little or no guidance on identifying those at increased risk of reduced BMD or fragility fracture. Preventative and therapeutic strategies with bone specific treatments need to be developed. Limited data suggest bisphosphonates may be beneficial in conjunction with vitamin D and calcium supplementation in the treatment of reduced BMD in HIV-infected patients but larger studies of longer duration are needed. The safety and cost-effectiveness of these and other treatments needs to be evaluated. Copyright © 2010. Published by Elsevier Inc.

  9. Damped-dynamics flexible fitting.

    Science.gov (United States)

    Kovacs, Julio A; Yeager, Mark; Abagyan, Ruben

    2008-10-01

    In fitting atomic structures into EM maps, it often happens that the map corresponds to a different conformation of the structure. We have developed a new methodology to handle these situations that preserves the covalent geometry of the structure and allows the modeling of large deformations. The first goal is achieved by working in generalized coordinates (positional and internal coordinates), and the second by avoiding harmonic potentials. Instead, we use dampers (shock absorbers) between every pair of atoms, combined with a force field that attracts the atomic structure toward incompletely occupied regions of the EM map. The trajectory obtained by integrating the resulting equations of motion converges to a conformation that, in our validation cases, was very close to the target atomic structure. Compared to current methods, our approach is more efficient and robust against wrong solutions and to overfitting, and does not require user intervention or subjective decisions. Applications to the computation of transition pathways between known conformers, homology and loop modeling, as well as protein docking, are also discussed.

  10. The best-fit universe

    International Nuclear Information System (INIS)

    Turner, M.S.; Chicago Univ., IL

    1990-10-01

    Inflation provides very strong motivation for a flat Universe, Harrison-Zel'dovich (constant-curvature) perturbations, and cold dark matter. However, there are a number of cosmological observations that conflict with the predictions of the simplest such model -- one with zero cosmological constant. They include the age of the Universe, dynamical determinations of Ω, galaxy-number counts, and the apparent abundance of large-scale structure in the Universe. While the discrepancies are not yet serious enough to rule out the simplest and ''most well motivated'' model, the current data point to a ''best-fit model'' with the following parameters: Ω B ≅ 0.03, Ω CDM ≅ 0.17, Ω Λ ≅ 0.8, and H 0 ≅ 70 km sec -1 Mpc -1 , which improves significantly the concordance with observations. While there is no good reason to expect such a value for the cosmological constant, there is no physical principle that would rule out such. 42 refs

  11. The best-fit universe

    Energy Technology Data Exchange (ETDEWEB)

    Turner, M.S. (Fermi National Accelerator Lab., Batavia, IL (USA) Chicago Univ., IL (USA). Enrico Fermi Inst.)

    1990-10-01

    Inflation provides very strong motivation for a flat Universe, Harrison-Zel'dovich (constant-curvature) perturbations, and cold dark matter. However, there are a number of cosmological observations that conflict with the predictions of the simplest such model -- one with zero cosmological constant. They include the age of the Universe, dynamical determinations of {Omega}, galaxy-number counts, and the apparent abundance of large-scale structure in the Universe. While the discrepancies are not yet serious enough to rule out the simplest and most well motivated'' model, the current data point to a best-fit model'' with the following parameters: {Omega}{sub B} {approx equal} 0.03, {Omega}{sub CDM} {approx equal} 0.17, {Omega}{sub {Lambda}} {approx equal} 0.8, and H{sub 0} {approx equal} 70 km sec{sup {minus}1} Mpc{sup {minus}1}, which improves significantly the concordance with observations. While there is no good reason to expect such a value for the cosmological constant, there is no physical principle that would rule out such. 42 refs.

  12. FItness programy a individuální přístup ve fitness

    OpenAIRE

    Rambous, Milan

    2008-01-01

    Souhrn: Tato diplomová práce se zabývá problematikou fitness programů a individuálru'ho přístupu ve fitness centrech. Celé téma zahrnuje rozpracování postupu při vytváření fitness programů a roli osobního trenéra ve fitness. Dále jsou zde uvedeny specifika některých fitness programů a v empirické části pak příklad dvou individuálních fitness programů. Název práce: Fitness programy a individuálnípřístup ve fitness Title: FITNESS PROGRAMS AND INDIVIDUAL CARE IN FITNESS Cíle práce: 1. podrobný p...

  13. When did HIV incidence peak in Harare, Zimbabwe? Back-calculation from mortality statistics.

    Directory of Open Access Journals (Sweden)

    Ben Lopman

    2008-03-01

    Full Text Available HIV prevalence has recently begun to decline in Zimbabwe, a result of both high levels of AIDS mortality and a reduction in incident infections. An important component in understanding the dynamics in HIV prevalence is knowledge of past trends in incidence, such as when incidence peaked and at what level. However, empirical measurements of incidence over an extended time period are not available from Zimbabwe or elsewhere in sub-Saharan Africa. Using mortality data, we use a back-calculation technique to reconstruct historic trends in incidence. From AIDS mortality data, extracted from death registration in Harare, together with an estimate of survival post-infection, HIV incidence trends were reconstructed that would give rise to the observed patterns of AIDS mortality. Models were fitted assuming three parametric forms of the incidence curve and under nine different assumptions regarding combinations of trends in non-AIDS mortality and patterns of survival post-infection with HIV. HIV prevalence was forward-projected from the fitted incidence and mortality curves. Models that constrained the incidence pattern to a cubic spline function were flexible and produced well-fitting, realistic patterns of incidence. In models assuming constant levels of non-AIDS mortality, annual incidence peaked between 4 and 5% between 1988 and 1990. Under other assumptions the peak level ranged from 3 to 8% per annum. However, scenarios assuming increasing levels of non-AIDS mortality resulted in implausibly low estimates of peak prevalence (11%, whereas models with decreasing underlying crude mortality could be consistent with the prevalence and mortality data. HIV incidence is most likely to have peaked in Harare between 1988 and 1990, which may have preceded the peak elsewhere in Zimbabwe. This finding, considered alongside the timing and location of HIV prevention activities, will give insight into the decline of HIV prevalence in Zimbabwe.

  14. Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

    Directory of Open Access Journals (Sweden)

    Vladimir Novitsky

    2011-02-01

    Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

  15. Adherence to feeding guidelines among HIV-infected and HIV ...

    African Journals Online (AJOL)

    For infants older than six months, complementary feeding was more common among HIV-uninfected (100%) than HIV-infected mothers (41.7%; P<0.001). Among infants of all ages, none of the HIV-uninfected and 45% of HIV-infected mothers were replacement feeding (p<0.001). More than a half (59.8%) of the mothers ...

  16. Physical characteristics related to bra fit.

    Science.gov (United States)

    Chen, Chin-Man; LaBat, Karen; Bye, Elizabeth

    2010-04-01

    Producing well-fitting garments has been a challenge for retailers and manufacturers since mass production began. Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. Because body contours are important factors affecting bra fit, this study analyses the relationship of physical characteristics to bra-fit problems. This study has used 3-D body-scanning technology to extract upper body angles from a sample of 103 college women; these data were used to categorise physical characteristics into shoulder slope, bust prominence, back curvature and acromion placement. Relationships between these physical categories and bra-fit problems were then analysed. Results show that significant main effects and two-way interactions of the physical categories exist in the fit problems of poor bra support and bra-motion restriction. The findings are valuable in helping the apparel industry create better-fitting bras. STATEMENT OF RELEVANCE: Poorly fitted bras can cause discomfort or pain and result in lost sales for retailers. The findings regarding body-shape classification provide researchers with a statistics method to quantify physical characteristics and the findings regarding the relationship analysis between physical characteristics and bra fit offer bra companies valuable information about bra-fit perceptions attributable to women with figure variations.

  17. HIV Status Discordance: Associated Factors Among HIV Positive ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    infection for a partner of a person with HIV is about 10%, with higher annual transmission rates ... We recommend the tracking of both men and women as index cases in other to reduce HIV .... HIV status was accepted as known only if backed.

  18. Bone mineral density abnormalities in HIV infected patients and HIV ...

    African Journals Online (AJOL)

    Bone mineral density abnormalities in HIV infected patients and HIV ... Comprehensive Care Clinic (CCC) and a HIV negative control group seen at the ... Older patients had lower levels of BMD (i.e. more negative BMD. p-value = 0.032).

  19. Living with HIV: Patients Perspective

    Centers for Disease Control (CDC) Podcasts

    This podcast showcases three people who are living with HIV. The patients share their experiences of being diagnosed with HIV, of the treatments they are undergoing, and on taking responsibility for their health.

  20. HIV/AIDS and Infections

    Science.gov (United States)

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

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV Learn the Link - Drugs and HIV ... Drugs can change the way the brain works, disrupting the parts of the brain that people use to weigh risks and benefits when making decisions. ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

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

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... PSA) where an HIV-positive teenager recounts the night she went to a party and under the ... party could change their lives , but now their night out always will be associated with HIV/AIDS. ...

  5. Drugs + HIV, Learn the Link

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

  6. Drugs + HIV, Learn the Link

    Medline Plus

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

  7. Drugs + HIV, Learn the Link

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

  8. Drugs + HIV, Learn the Link

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

  9. Drugs + HIV, Learn the Link

    Medline Plus

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

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... associated with drug misuse are among the main factors in the spread of HIV infection in the ... associated with drug misuse are among the main factors in the spread of HIV infection in the ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of people infected with HIV, drug misuse can interfere with an individual's likelihood of adhering to the ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... who use methamphetamine than among HIV patients who do not misuse drugs. In animal studies, methamphetamine has ... risk, trends in HIV/AIDS, and what to do to counter these trends. Online Resources NIDA for ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the main factors in the spread of HIV infection in the United States. Drugs can change the ... about the link between drug misuse and HIV infection. It contains information for young people, parents and ...

  14. Pediatric HIV in Kano, Nigeria

    African Journals Online (AJOL)

    2013-02-15

    Feb 15, 2013 ... HIV‑infected children were enrolled into HIV care and followed up for 6 months. ..... the HIV infection, particularly from diarrhoea and anorexia resulting from ... improved socio‑economic status, and improved nutrition should be ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

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

  16. Drugs + HIV, Learn the Link

    Medline Plus

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

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV patients who do not misuse drugs. In animal studies, methamphetamine has been shown to increase the amount of HIV in brain cells 1 . Drug use disorder treatment. Since the late ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... drug injection paraphernalia—HIV can be transmitted between users. Other infections, such as hepatitis C, can also ... also serve an important role in providing current information on HIV/AIDS and related diseases, counseling and ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... that is crucial to the normal function of the human immune system. Loss of these CD4+ cells in ... AIDS. Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

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

  1. Drugs + HIV, Learn the Link

    Medline Plus

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

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... NIDA Director's Page Organization Legislative Activities Advisory Boards & ... "HIV/AIDS." HIV can be transferred between people if an infected person's blood or other bodily fluid comes in contact with ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV infection in the United States. Drugs can change the way the brain works, disrupting the parts ... HIV infection in the United States. Drugs can change the way the brain works, disrupting the parts ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

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

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS ... produced a set of multicultural public service announcements (PSAs) that use text messaging ...

  6. HIV: Social and Environmental Factors

    Centers for Disease Control (CDC) Podcasts

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses how social and environmental factors may put African Americans at greater risk for HIV.

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This site provides information both for health care providers and for Veterans and the public. Send ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental ... suppress the virus and prevent or decrease symptoms of illness. To learn about current statistics of HIV in ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

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

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drug Misuse Hepatitis (Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain ... brain. Research has shown that HIV causes greater injury to cells in the brain and cognitive impairment ...

  11. UCSF Center for HIV Information

    Science.gov (United States)

    ... from the UCSF Positive Health Program HIV/AIDS Clinic (Ward 86) at San Francisco General Hospital This series offers clinical practice recommendations for management of HIV-related conditions from the expert clinicians ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... for contracting HIV. In general, middle and late teen years are when young people engage in risk-taking and sensation-seeking behaviors. Unsafe sexual practices increase a person's risk of contracting HIV, ...

  13. HIV 1065_IN.indd

    African Journals Online (AJOL)

    disease. is case highlights the diagnostic value of lymph node excision biopsy in HIV-infected patients. S Afr J HIV .... illustrated that life expectancy in multicentric ... Schulte KM, Talat N. Castleman's disease: A two compartment model of HHV.

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... their compromised immune system, people with AIDS often develop serious infections or cancers, and they frequently suffer ... Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

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

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to HIV and progression of ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... between drug misuse and HIV/AIDS. In the early years of the HIV epidemic, it became clear ... Children, Youth and Families The American Academy of Child & Adolescent Psychiatry (AACAP) The United Negro College Fund, ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

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

  19. Drugs + HIV, Learn the Link

    Medline Plus

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

  20. Living with HIV: Patients Perspective

    Centers for Disease Control (CDC) Podcasts

    2009-06-04

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

  1. Inclusive Fitness Maximization:An Axiomatic Approach

    OpenAIRE

    Okasha, Samir; Weymark, John; Bossert, Walter

    2014-01-01

    Kin selection theorists argue that evolution in social contexts will lead organisms to behave as if maximizing their inclusive, as opposed to personal, fitness. The inclusive fitness concept allows biologists to treat organisms as akin to rational agents seeking to maximize a utility function. Here we develop this idea and place it on a firm footing by employing a standard decision-theoretic methodology. We show how the principle of inclusive fitness maximization and a related principle of qu...

  2. [Person-organization fit and work ability].

    Science.gov (United States)

    Merecz, Dorota; Andysz, Aleksandra

    2011-01-01

    Person-environment issue has long been in focus of researchers who explore the area of human labor. It is known that the level of fit is a predictor of many phenomena related to health and attitude to work. The aim of this study was to explore the association between the level of person- organization fit (P-O fit) and work ability, including indicators of somatic and mental health. Research was conducted on a representative sample of 600 Polish men and women at working age. The Person-Organization Fit Questionnaire was used to assess three dimensions of P-O fit (supplementary fit, complementary fit and identification with organization); mental health status was measured by GHQ-28; the number of diagnosed diseases was taken as an index of somatic health; work ability, ability to physical and mental efforts were measured by three items from the Work Ability Index. A significant relationship between P-O fit level and work ability was found. In men, work ability predictors were: age, supplementary fit and mental health status, which explained 25% of the variance in work ability. In women, work ability predictors were: the number of diagnosed somatic diseases, supplementary fit, age and complementary fit, which explained 27% of the variance in work ability. Some gender-related differences in the predictive value of variables under the study were also found. The results of this study indicate the importance of P-O fit in shaping the sense of work ability, a recognized predictor of workers' occupational activity and the frequency of taking sick leave in subsequent years. Therefore, this result may be a useful argument to motivate employers to employ workers adequately to their abilities and preferences.

  3. Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

    Science.gov (United States)

    Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

    2016-06-01

    Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

  4. Handling of computational in vitro/in vivo correlation problems by Microsoft Excel II. Distribution functions and moments.

    Science.gov (United States)

    Langenbucher, Frieder

    2003-01-01

    MS Excel is a useful tool to handle in vitro/in vivo correlation (IVIVC) distribution functions, with emphasis on the Weibull and the biexponential distribution, which are most useful for the presentation of cumulative profiles, e.g. release in vitro or urinary excretion in vivo, and differential profiles such as the plasma response in vivo. The discussion includes moments (AUC and mean) as summarizing statistics, and data-fitting algorithms for parameter estimation.

  5. The Obesity Paradox and Cardiorespiratory Fitness

    Directory of Open Access Journals (Sweden)

    Paul A. McAuley

    2012-01-01

    Full Text Available Cardiorespiratory fitness as an explanation for the obesity paradox warrants further examination. We evaluated independent and joint associations of cardiorespiratory fitness and adiposity with all-cause mortality in 811 middle-aged (age, 53.3±7.2 years male never smokers without documented cardiopulmonary disease or diabetes from the Veterans Exercise Testing Study (VETS. Cardiorespiratory fitness was quantified in metabolic equivalents (METs using final treadmill speed and grade achieved on a maximal exercise test. Subjects were grouped for analysis by METs: unfit (lowest third and fit (upper two-thirds; and by body mass index (kg/m2: nonobese (18.5−29.9 and obese (≥30.0. Associations of baseline fitness and adiposity measures with all-cause mortality were determined by Cox proportional hazards analysis adjusted for age, ethnicity, hypertension, hypercholesterolemia, family history of coronary artery disease, and cardiovascular medication use. In multivariate analysis, mortality risk for obese/fit men did not differ significantly from the nonobese/fit reference group. However, compared to the reference group, nonobese and obese unfit men were 2.2 (=0.01 and 1.9 (=0.03 times more likely to die, respectively. Cardiorespiratory fitness altered the obesity paradox such that mortality risk was lower for both obese and nonobese men who were fit.

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... women can pass HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV treatment and prevention clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... AIDSinfo, a service of the U.S. Department of Health and Human Services (HHS), offers access to the latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention ... for health care providers, researchers, people affected by HIV/AIDS, ...

  9. HIV Infection and Cancer Risk

    Science.gov (United States)

    ... same age ( 1 ). The general term for these cancers is "HIV-associated cancers." Three of these cancers are known as " acquired ... also have an increased cumulative risk of developing HIV-associated cancers. What can people infected with HIV do to ...

  10. What Is HIV/AIDS?

    Science.gov (United States)

    ... take their HIV medications as directed, and different health-related choices they make, such as decisions to eat a healthful diet , exercise , and not smoke . Is There a Cure for HIV? No effective cure currently exists for HIV. But with proper ...

  11. Textbook of pediatric HIV care

    National Research Council Canada - National Science Library

    Read, Jennifer S; Zeichner, Steven L. (Steven Leonard)

    2005-01-01

    ... and the opportunistic infections that accompany HIV infection have been developed, accompanied by many new ways of monitoring HIV infection in children. These new therapies and approaches to management are complicated, but the long-term health of HIV-infected children depends on their meticulously correct application. This textbook explains, helps and guides...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... response to HIV/AIDS, as well as HIV/AIDS research and policies. AIDS.gov New Media Tools : These new media tools ... offers access to the latest, federally approved HIV/AIDS medical practice ... information for health care providers, researchers, people affected ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... at: http://www.drugabuse.gov/news-events/public-education-projects/learn-link-drugs-hiv . 120x90 460x80 486x60 ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe sexual practices, which put people at risk for getting HIV or transmitting it to someone ... HIV, and using drugs and alcohol can increase the chances of unsafe behavior by ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to cells in the brain and cognitive impairment among people who use methamphetamine than among HIV patients who do not misuse drugs. In animal studies, methamphetamine has been shown to increase the amount ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention clinical trials, and other research information ... of this virus. Although we currently have medical therapies that ... infected with HIV, drug misuse can interfere with an individual's likelihood ...

  17. Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages.

    Directory of Open Access Journals (Sweden)

    Weibin Zha

    Full Text Available HIV protease inhibitor (PI-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR, a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp in HIV PI-mediated accumulation of BBR in macrophages.Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT and human P-gp transfected (MDCK/P-gp cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123 efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp.HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic.

  18. A person-environment fit approach to volunteerism : Volunteer personality fit and culture fit as predictors of affective outcomes

    NARCIS (Netherlands)

    Van Vianen, Annelies E. M.; Nijstad, Bernard A.; Voskuijl, Olga F.

    2008-01-01

    This study employed a person-environment (P-E) fit approach to explaining volunteer satisfaction, affective commitment, and turnover intentions. It was hypothesized that personality fit would explain additional variance in volunteer affective outcomes above and beyond motives to volunteer. This

  19. HIV stigma and social capital in women living with HIV

    OpenAIRE

    Cuca, Yvette P.; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

    2016-01-01

    Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total so...

  20. HIV-1 vaccines

    Science.gov (United States)

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

    2014-01-01

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