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Sample records for expanded hiv tropism

  1. Species tropism of HIV-1 modulated by viral accessory proteins

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    Masako eNomaguchi; Naoya eDoi; Yui eMatsumoto; Yosuke eSakai; Sachi eFujiwara; Akio eAdachi

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) is tropic and pathogenic only for humans, and does not replicate in macaque monkeys routinely used for experimental infections. This specially narrow host range (species tropism) has impeded much the progress of HIV-1/acquired immunodeficiency syndrome (AIDS) basic research. Extensive studies on the underlying mechanism have revealed that Vif, one of viral accessory proteins, is critical for the HIV-1 species tropism in addition to Gag-capsid protei...

  2. HIV tropism and decreased risk of breast cancer.

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    Nancy A Hessol

    2010-12-01

    Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

  3. Expanded Tropism and Altered Activation of a Retroviral Glycoprotein Resistant to an Entry Inhibitor Peptide

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    Amberg, Sean M.; Netter, Robert C.; Simmons, Graham; Bates, Paul

    2006-01-01

    The envelope of class I viruses can be a target for potent viral inhibitors, such as the human immunodeficiency virus type 1 (HIV-1) inhibitor enfuvirtide, which are derived from the C-terminal heptad repeat (HR2) of the transmembrane (TM) subunit. Resistance to an HR2-based peptide inhibitor of a model retrovirus, subgroup A of the Avian Sarcoma and Leukosis Virus genus (ASLV-A), was studied by examining mutants derived by viral passage in the presence of inhibitor. Variants with reduced sensitivity to inhibitor were readily selected in vitro. Sensitivity determinants were identified for 13 different isolates, all of which mapped to the TM subunit. These determinants were identified in two regions: (i) the N-terminal heptad repeat (HR1) and (ii) the N-terminal segment of TM, between the subunit cleavage site and the fusion peptide. The latter class of mutants identified a region outside of the predicted HR2-binding site that can significantly alter sensitivity to inhibitor. A subset of the HR1 mutants displayed the unanticipated ability to infect nonavian cells. This expanded tropism was associated with increased efficiency of envelope triggering by soluble receptor at low temperatures, as measured by protease sensitivity of the surface subunit (SU) of envelope. In addition, expanded tropism was linked for the most readily triggered mutants with increased sensitivity to neutralization by SU-specific antiserum. These observations depict a class of HR2 peptide-selected mutations with a reduced activation threshold, thereby allowing the utilization of alternative receptors for viral entry. PMID:16352560

  4. HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.

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    Pou, Christian; Codoñer, Francisco M; Thielen, Alexander; Bellido, Rocío; Pérez-Álvarez, Susana; Cabrera, Cecilia; Dalmau, Judith; Curriu, Marta; Lie, Yolanda; Noguera-Julian, Marc; Puig, Jordi; Martínez-Picado, Javier; Blanco, Julià; Coakley, Eoin; Däumer, Martin; Clotet, Bonaventura; Paredes, Roger

    2013-01-01

    Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA evolution in PBMCs during viremia suppression and only found evolution of R5 viruses in one subject. No de novo CXCR4-using HIV-1 production was observed over time. Finally, Slatkin-Maddison tests suggested that plasma and cell-associated V3 forms were sometimes compartmentalized. The absence of tropism shifts during viremia suppression suggests that, when available, testing of stored plasma samples is generally safe and informative, provided that HIV-1 suppression is maintained. Tropism testing in PBMCs may not necessarily produce equivalent biological results to plasma, because the structure of viral populations and the diagnostic performance of tropism assays may sometimes vary between compartments. Thereby, proviral DNA tropism testing should be specifically validated in clinical trials before it can be applied to routine clinical decision-making.

  5. Pace of Coreceptor Tropism Switch in HIV-1-Infected Individuals after Recent Infection.

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    Arif, Muhammad Shoaib; Hunter, James; Léda, Ana Rachel; Zukurov, Jean Paulo Lopes; Samer, Sadia; Camargo, Michelle; Galinskas, Juliana; Kallás, Esper Georges; Komninakis, Shirley Vasconcelos; Janini, Luiz Mario; Sucupira, Maria Cecilia; Diaz, Ricardo Sobhie

    2017-10-01

    HIV-1 entry into target cells influences several aspects of HIV-1 pathogenesis, including viral tropism, HIV-1 transmission and disease progression, and response to entry inhibitors. The evolution from CCR5- to CXCR4-using strains in a given human host is still unpredictable. Here we analyzed timing and predictors for coreceptor evolution among recently HIV-1-infected individuals. Proviral DNA was longitudinally evaluated in 66 individuals using Geno2pheno[coreceptor] Demographics, viral load, CD4+ and CD8+ T cell counts, CCR5Δ32 polymorphisms, GB virus C (GBV-C) coinfection, and HLA profiles were also evaluated. Ultradeep sequencing was performed on initial samples from 11 selected individuals. A tropism switch from CCR5- to CXCR4-using strains was identified in 9/49 (18.4%) individuals. Only a low baseline false-positive rate (FPR) was found to be a significant tropism switch predictor. No minor CXCR4-using variants were identified in initial samples of 4 of 5 R5/non-R5 switchers. Logistic regression analysis showed that patients with an FPR of >40.6% at baseline presented a stable FPR over time whereas lower FPRs tend to progressively decay, leading to emergence of CXCR4-using strains, with a mean evolution time of 27.29 months (range, 8.90 to 64.62). An FPR threshold above 40.6% determined by logistic regression analysis may make it unnecessary to further determine tropism for prediction of disease progression related to emergence of X4 strains or use of CCR5 antagonists. The detection of variants with intermediate FPRs and progressive FPR decay over time not only strengthens the power of Geno2pheno in predicting HIV tropism but also indirectly confirms a continuous evolution from earlier R5 variants toward CXCR4-using strains.IMPORTANCE The introduction of CCR5 antagonists in the antiretroviral arsenal has sparked interest in coreceptors utilized by HIV-1. Despite concentrated efforts, viral and human host features predicting tropism switch are still poorly

  6. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

    DEFF Research Database (Denmark)

    Fontdevila, Maria Casadellà; Cozzi-Lepri, Alessandro; Phillips, Andrew

    2014-01-01

    INTRODUCTION: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA...... was observed between tropism and ART status. There were no significant differences in the CD4+ slope within or between tropism groups. CONCLUSIONS: Plasma HIV-1 tropism does not appear to add to the ability of CD4 count and viral load to predict the short term risk of AIDS and death outcomes, even with 454...... level >1000 copies/mL, including both people on ART and those ART naïve. METHODS: People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL)≥1,000 copies/mL available in the time window of 3-12 months prior to the event were identified...

  7. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

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    John Archer

    Full Text Available HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5 viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences and genotypic (e.g., population sequencing linked to bioinformatic algorithms assays are the most widely used. Although several next-generation sequencing (NGS platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences, Illumina®, and Ion Torrent™ (Life Technologies. Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used, compared to Trofile (80% and population sequencing (70%. In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  8. Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or death

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    Maria Casadellà Fontdevila

    2014-11-01

    Full Text Available Introduction: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case-control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve. Methods: People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV-1 RNA (VL≥1,000 copies/mL available in the time window of 3–12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event-free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS. Non-R5 HIV was defined as: (a ≥2% of sequences with a Geno2Pheno (G2P FPR≤3.75% by 454, and (b a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status. Results: The study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non-R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART-naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm3 and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038, CD4+ count (OR=0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00; p=0.058, being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022 and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0

  9. Use of Four Next-Generation Sequencing Platforms to Determine HIV-1 Coreceptor Tropism

    Czech Academy of Sciences Publication Activity Database

    Archer, J.; Weber, Jan; Henry, K.; Winner, D.; Gibson, R.; Lee, L.; Paxinos, E.; Arts, E. J.; Robertson, D. L.; Mimms, L.; Quinones-Mateu, M. E.

    2012-01-01

    Roč. 7, č. 11 (2012), e49602/1-e49602/17 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LK11207 Institutional research plan: CEZ:AV0Z40550506 Keywords : HIV -1 tropism * V3 region * deep sequencing Subject RIV: EE - Microbiology, Virology Impact factor: 3.730, year: 2012 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049602

  10. Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India

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    Kuttiatt Vijesh S

    2010-07-01

    Full Text Available Abstract Background Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine using in silico methods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences. Results R5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months compared to R5-tropic strains (20.5 months. Conclusions High prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.

  11. Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay.

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    van der Ryst, Elna; Heera, Jayvant; Demarest, James; Knirsch, Charles

    2015-06-01

    Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32-bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5-tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofile™, a novel phenotypic tropism assay, was used to identify patients with CCR5-tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed. © 2015 New York Academy of Sciences.

  12. DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS

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    Liã Bárbara Arruda

    2014-07-01

    Full Text Available The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.

  13. Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death

    DEFF Research Database (Denmark)

    Casadellà, Maria; Cozzi-Lepri, Alessandro; Phillips, Andrew

    2017-01-01

    OBJECTIVE: To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. DESIGN: Nested case-control study within the EuroSIDA cohort. METHODS: Cases were subjects with AIDS or who died from any cause, with...

  14. Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death.

    Science.gov (United States)

    Casadellà, Maria; Cozzi-Lepri, Alessandro; Phillips, Andrew; Noguera-Julian, Marc; Bickel, Markus; Sedlacek, Dalibor; Zilmer, Kai; Clotet, Bonaventura; Lundgren, Jens D; Paredes, Roger

    2017-01-01

    To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. Nested case-control study within the EuroSIDA cohort. Cases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling. The study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, pdeath. CD4+T-cell slopes did not differ within or between tropism groups. The predictive role of plasma tropism determined using 454 sequencing in the context of people receiving cART with detectable VL is not helpful to identify subjects at higher risk for clinical progression to AIDS or death.

  15. Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

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    Flávia Jacqueline Almeida

    Full Text Available Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir CD4 documented during follow-up (p < 0.0001 and with disease severity (clinical event and/or CD4 below 200 cells/mm3 at the last observation, using commonly applied clinical cutoffs, such as10%FPRclonal (p = 0.001. When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73 were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.

  16. Appraising the performance of genotyping tools in the prediction of coreceptor tropism in HIV-1 subtype C viruses

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    Crous Saleema

    2012-09-01

    Full Text Available Abstract Background In human immunodeficiency virus type 1 (HIV-1 infection, transmitted viruses generally use the CCR5 chemokine receptor as a coreceptor for host cell entry. In more than 50% of subtype B infections, a switch in coreceptor tropism from CCR5- to CXCR4-use occurs during disease progression. Phenotypic or genotypic approaches can be used to test for the presence of CXCR4-using viral variants in an individual’s viral population that would result in resistance to treatment with CCR5-antagonists. While genotyping approaches for coreceptor-tropism prediction in subtype B are well established and verified, they are less so for subtype C. Methods Here, using a dataset comprising V3 loop sequences from 349 CCR5-using and 56 CXCR4-using HIV-1 subtype C viruses we perform a comparative analysis of the predictive ability of 11 genotypic algorithms in their prediction of coreceptor tropism in subtype C. We calculate the sensitivity and specificity of each of the approaches as well as determining their overall accuracy. By separating the CXCR4-using viruses into CXCR4-exclusive (25 sequences and dual-tropic (31 sequences we evaluate the effect of the possible conflicting signal from dual-tropic viruses on the ability of a of the approaches to correctly predict coreceptor phenotype. Results We determined that geno2pheno with a false positive rate of 5% is the best approach for predicting CXCR4-usage in subtype C sequences with an accuracy of 94% (89% sensitivity and 99% specificity. Contrary to what has been reported for subtype B, the optimal approaches for prediction of CXCR4-usage in sequence from viruses that use CXCR4 exclusively, also perform best at predicting CXCR4-use in dual-tropic viral variants. Conclusions The accuracy of genotyping approaches at correctly predicting the coreceptor usage of V3 sequences from subtype C viruses is very high. We suggest that genotyping approaches can be used to test for coreceptor tropism in HIV-1

  17. The temporal increase in HIV-1 non-R5 tropism frequency among newly diagnosed patients from northern Poland is associated with clustered transmissions

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    Miłosz Parczewski

    2015-08-01

    Full Text Available Introduction: CCR5 (R5 tropic viruses are associated with early stages of infection, whereas CXCR4 (X4 HIV-1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype-predicted tropism frequency and the phylogenetic relationships between the R5 and non-R5 clades. Methods: A cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV-1 genotypic tropism with triplicate V3-loop sequencing. The non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference. Results: The overall non-R5 tropism frequency for 5.75% FPR was 15.5% (n=30 and 27.8% (n=54 for 10% FPR. The frequency of the non-R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0% to 2014 (n=5/17, 29.4% (p=0.004, rough slope +3.73%/year and from 0% (2007 to 35.3% (2014, n=6/17 (p=0.071, rough slope +2.9%/year using 10% FPR. Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope +3.53%/year along with a tendency to increase the lymphocyte CD4 nadir (p=0.069. Thirty-two clusters were identified, and non-R5 tropic viruses were found for 26 (30.95% sequences contained within 14 (43.8% clusters. Non-R5 tropism was associated with subtype D variants (p=0.0001 and the presence of CCR5 Δ32/wt genotype (p=0.052. Conclusions: R5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non-R5 tropic variants may limit the clinical efficacy of the co-receptor inhibitors. The rising prevalence of non-R5 HIV-1 may indicate transmission of X4 clades.

  18. A single gp120 residue can affect HIV-1 tropism in macaques.

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    Gregory Q Del Prete

    2017-09-01

    Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

  19. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5

    Energy Technology Data Exchange (ETDEWEB)

    Mefford, Megan E., E-mail: megan_mefford@hms.harvard.edu [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA (United States); Kunstman, Kevin, E-mail: kunstman@northwestern.edu [Northwestern University Medical School, Chicago, IL (United States); Wolinsky, Steven M., E-mail: s-wolinsky@northwestern.edu [Northwestern University Medical School, Chicago, IL (United States); Gabuzda, Dana, E-mail: dana_gabuzda@dfci.harvard.edu [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Neurology (Microbiology and Immunobiology), Harvard Medical School, Boston, MA (United States)

    2015-07-15

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120–CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. - Highlights: • We analyze HIV Env sequences and identify amino acids in beta 3 of the gp120 bridging sheet that enhance macrophage tropism. • These amino acids at positions 197 and 200 are present in brain of some patients with HIV-associated dementia. • D197 results in loss of a glycan near the HIV Env trimer apex, which may increase exposure of V3. • These variants may promote infection of macrophages in the brain by enhancing gp120–CCR5 interactions.

  20. The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors.

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    Valentina Gatta

    2015-05-01

    Full Text Available Herpes simplex virus (HSV enters cells by means of four essential glycoproteins - gD, gH/gL, gB, activated in a cascade fashion by gD binding to one of its receptors, nectin1 and HVEM. We report that the engineering in gH of a heterologous ligand - a single-chain antibody (scFv to the cancer-specific HER2 receptor - expands the HSV tropism to cells which express HER2 as the sole receptor. The significance of this finding is twofold. It impacts on our understanding of HSV entry mechanism and the design of retargeted oncolytic-HSVs. Specifically, entry of the recombinant viruses carrying the scFv-HER2-gH chimera into HER2+ cells occurred in the absence of gD receptors, or upon deletion of key residues in gD that constitute the nectin1/HVEM binding sites. In essence, the scFv in gH substituted for gD-mediated activation and rendered a functional gD non-essential for entry via HER2. The activation of the gH moiety in the chimera was carried out by the scFv in cis, not in trans as it occurs with wt-gD. With respect to the design of oncolytic-HSVs, previous retargeting strategies were based exclusively on insertion in gD of ligands to cancer-specific receptors. The current findings show that (i gH accepts a heterologous ligand. The viruses retargeted via gH (ii do not require the gD-dependent activation, and (iii replicate and kill cells at high efficiency. Thus, gH represents an additional tool for the design of fully-virulent oncolytic-HSVs retargeted to cancer receptors and detargeted from gD receptors.

  1. HIV-1 Tropism Dynamics and Phylogenetic Analysis from Longitudinal Ultra-Deep Sequencing Data of CCR5- and CXCR4-Using Variants

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    Sede, Mariano M.; Moretti, Franco A.; Laufer, Natalia L.

    2014-01-01

    Objective Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. The molecular and evolutionary mechanisms underlying the CCR5 to CXCR4 switch are the focus of intense recent research. We studied the HIV-1 tropism dynamics in relation to coreceptor usage, the nature of quasispecies from ultra deep sequencing (UDPS) data and their phylogenetic relationships. Methods Here, we characterized C2-V3-C3 sequences of HIV obtained from 19 patients followed up for 54 to 114 months using UDPS, with further genotyping and phylogenetic analysis for coreceptor usage. HIV quasispecies diversity and variability as well as HIV plasma viral load were measured longitudinally and their relationship with the HIV coreceptor usage was analyzed. The longitudinal UDPS data were submitted to phylogenetic analysis and sampling times and coreceptor usage were mapped onto the trees obtained. Results Although a temporal viral genetic structuring was evident, the persistence of several viral lineages evolving independently along the infection was statistically supported, indicating a complex scenario for the evolution of viral quasispecies. HIV X4-using variants were present in most of our patients, exhibiting a dissimilar inter- and intra-patient predominance as the component of quasispecies even on antiretroviral therapy. The viral populations from some of the patients studied displayed evidences of the evolution of X4 variants through fitness valleys, whereas for other patients the data favored a gradual mode of emergence. Conclusions CXCR4 usage can emerge independently, in multiple lineages, along the course of HIV infection. The mode of emergence, i.e. gradual or through fitness valleys seems to depend on both virus and patient factors. Furthermore, our analyses suggest that, besides becoming dominant after population-level switches, minor proportions of X4 viruses might exist along the infection, perhaps even at early stages of it. The fate of these minor

  2. HIV-1 tropism dynamics and phylogenetic analysis from longitudinal ultra-deep sequencing data of CCR5- and CXCR4-using variants.

    Science.gov (United States)

    Sede, Mariano M; Moretti, Franco A; Laufer, Natalia L; Jones, Leandro R; Quarleri, Jorge F

    2014-01-01

    Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. The molecular and evolutionary mechanisms underlying the CCR5 to CXCR4 switch are the focus of intense recent research. We studied the HIV-1 tropism dynamics in relation to coreceptor usage, the nature of quasispecies from ultra deep sequencing (UDPS) data and their phylogenetic relationships. Here, we characterized C2-V3-C3 sequences of HIV obtained from 19 patients followed up for 54 to 114 months using UDPS, with further genotyping and phylogenetic analysis for coreceptor usage. HIV quasispecies diversity and variability as well as HIV plasma viral load were measured longitudinally and their relationship with the HIV coreceptor usage was analyzed. The longitudinal UDPS data were submitted to phylogenetic analysis and sampling times and coreceptor usage were mapped onto the trees obtained. Although a temporal viral genetic structuring was evident, the persistence of several viral lineages evolving independently along the infection was statistically supported, indicating a complex scenario for the evolution of viral quasispecies. HIV X4-using variants were present in most of our patients, exhibiting a dissimilar inter- and intra-patient predominance as the component of quasispecies even on antiretroviral therapy. The viral populations from some of the patients studied displayed evidences of the evolution of X4 variants through fitness valleys, whereas for other patients the data favored a gradual mode of emergence. CXCR4 usage can emerge independently, in multiple lineages, along the course of HIV infection. The mode of emergence, i.e. gradual or through fitness valleys seems to depend on both virus and patient factors. Furthermore, our analyses suggest that, besides becoming dominant after population-level switches, minor proportions of X4 viruses might exist along the infection, perhaps even at early stages of it. The fate of these minor variants might depend on both viral and host

  3. HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

    Directory of Open Access Journals (Sweden)

    Andre Minhoto Lanca

    2012-02-01

    Full Text Available While human immunodeficiency virus (HIV-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1 over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49. The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05. Moreover, higher false-positive rates (FPR values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001. Transmitted drug resistance mutations, documented in 3/41 (7.3% cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

  4. 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.

  5. An expanded model of HIV cell entry phenotype based on multi-parameter single-cell data

    Directory of Open Access Journals (Sweden)

    Bozek Katarzyna

    2012-07-01

    Full Text Available Abstract Background Entry of human immunodeficiency virus type 1 (HIV-1 into the host cell involves interactions between the viral envelope glycoproteins (Env and the cellular receptor CD4 as well as a coreceptor molecule (most importantly CCR5 or CXCR4. Viral preference for a specific coreceptor (tropism is in particular determined by the third variable loop (V3 of the Env glycoprotein gp120. The approval and use of a coreceptor antagonist for antiretroviral therapy make detailed understanding of tropism and its accurate prediction from patient derived virus isolates essential. The aim of the present study is the development of an extended description of the HIV entry phenotype reflecting its co-dependence on several key determinants as the basis for a more accurate prediction of HIV-1 entry phenotype from genotypic data. Results Here, we established a new protocol of quantitation and computational analysis of the dependence of HIV entry efficiency on receptor and coreceptor cell surface levels as well as viral V3 loop sequence and the presence of two prototypic coreceptor antagonists in varying concentrations. Based on data collected at the single-cell level, we constructed regression models of the HIV-1 entry phenotype integrating the measured determinants. We developed a multivariate phenotype descriptor, termed phenotype vector, which facilitates a more detailed characterization of HIV entry phenotypes than currently used binary tropism classifications. For some of the tested virus variants, the multivariant phenotype vector revealed substantial divergences from existing tropism predictions. We also developed methods for computational prediction of the entry phenotypes based on the V3 sequence and performed an extrapolating calculation of the effectiveness of this computational procedure. Conclusions Our study of the HIV cell entry phenotype and the novel multivariate representation developed here contributes to a more detailed

  6. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    Directory of Open Access Journals (Sweden)

    Masmudur M Rahman

    Full Text Available Myxoma virus (MYXV-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR and RNA helicase A (RHA/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication

  7. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    Science.gov (United States)

    Rahman, Masmudur M; Liu, Jia; Chan, Winnie M; Rothenburg, Stefan; McFadden, Grant

    2013-01-01

    Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid

  8. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Science.gov (United States)

    2010-08-19

    ... Announcement CDC-RFA-PS10-10138, ``Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately... Assistance Number: 93.523 The Affordable Care Act: Human Immunodeficiency Virus (HIV) Prevention and Public... Number 93.523 The Affordable Care Act: Human Immunodeficiency Virus (HIV) Prevention and Public Health...

  9. Cost effectiveness of expanded antenatal HIV testing in London

    NARCIS (Netherlands)

    Postma, MJ; Beck, EJ; Hankins, CA; Mandalia, S; Jager, JC; de Jong-van den Berg, LTW; Sherr, L

    2000-01-01

    Background: Recently the Department of Health announced the introduction in England of voluntary universal HIV screening in early pregnancy to prevent vertical transmission. New data have shown the importance of HIV infection in infants born to mothers who were HIV-negative in early pregnancy and

  10. Enhancing School HIV and AIDS Strategic Plan through Expanded Stakeholder Involvement

    Science.gov (United States)

    Mgomezulu, V. Y.; Kruger, A. G.

    2011-01-01

    This article focuses on the need for expanded stakeholder involvement as a means of enhancing the Botswana Department of Secondary Education (DSE) HIV and AIDS strategic plan. Research has indicated that the effects of HIV and AIDS on the supply of and demand for education are considerable. Using a questionnaire and interviews, the research has…

  11. INTRODUCTION The global HIV epidemic continues to expand with ...

    African Journals Online (AJOL)

    the HIV disease itself.9 During pregnancy, dosing must be taken into consideration as blood volume and volume of distribution changes during pregnancy. In addition, there are potential toxic drug effects on the ... myopathy may dictate change of anesthetic techniques. Anemia and thrombocytopenia are major toxic side.

  12. Expanding access to the management of HIV/ AIDS through ...

    African Journals Online (AJOL)

    Most of them referred to the mass media as their primary source of information. There is an urgent need for pro-active planning to prepare physicians in private practice for increasing demands in the management of HIV/AIDS in Nigeria. Organising a nation-wide training programme that would lead to ongoing accreditation ...

  13. Expanding HIV testing and linkage to care in southwestern Uganda with community health extension workers.

    Science.gov (United States)

    Asiimwe, Stephen; Ross, Jennifer M; Arinaitwe, Anthony; Tumusiime, Obed; Turyamureeba, Bosco; Roberts, D Allen; O'Malley, Gabrielle; Barnabas, Ruanne V

    2017-07-21

    Achieving the UNAIDS goals of 90-90-90 will require more than doubling the number of people accessing HIV care in Uganda. Community-based programmes for entry into HIV care are effective strategies to expand access to HIV care, but few programmes have been evaluated with a particular focus on scale-up. Integrated Community Based Initiatives, a Uganda-based non-governmental organization, designed and implemented a programme of community-based HIV counselling and testing and facilitated linkage to care utilizing community health extension workers (CHEWs) in rural Sheema District, Uganda. CHEWs performed programme activities during 1 October 2015 through 31 March 2016. Outcomes for this evaluation were (1) the number of people tested for HIV, and (2) the proportion of those testing positive who were seen at an ART clinic within three months of their positive test, and (3) the cost of the programme per person newly diagnosed with HIV. Microcosting methods were used to calculate the programme costs. Program scalability factors were evaluated using a published framework. Sixty-two CHEWs attended a five-day training that introduced the biology of HIV, the conduct of confidential HIV testing, HIV prevention messages, and linkage, referral, and reporting requirements. CHEWs received a $30 monthly stipend and a field testing kit that included a bicycle, field bag, umbrella, gumboots, reporting booklet, pens, and HIV testing materials. Trained CHEWs tested 43,696 persons for HIV infection during the six-month programme period. Nine-hundred seventy-four participants (2.2%) were identified as HIV positive, and 623 participants (64%) were linked to HIV care. An estimated 69% of adult residents received testing as part of this campaign. The programme cost $3.02 per person test, $135.70 per positive person identified, and $212.15 per HIV-positive person linked to care. Lay community health extension workers (CHEWs) can be rapidly trained to scale-up home-based HIV testing and

  14. Visualization of X4- and R5-Tropic HIV-1 Viruses Expressing Fluorescent Proteins in Human Endometrial Cells: Application to Tropism Study.

    Science.gov (United States)

    Terrasse, Rachel; Memmi, Meriam; Palle, Sabine; Heyndrickx, Leo; Vanham, Guido; Pozzetto, Bruno; Bourlet, Thomas

    2017-01-01

    Worldwide most HIV infections occur through heterosexual transmission, involving complex interactions of cell-free and cell-associated particles with cells of the female genital tract mucosa. The ability of HIV-1 to "infect" epithelial cells remains poorly understood. To address this question, replicative-competent chimeric constructs expressing fluorescent proteins and harboring the envelope of X4- or R5-tropic HIV-1 strains were used to "infect" endometrial HEC1-A cells. The virus-cell interactions were visualized using confocal microscopy (CM) at various times post infection. Combined with quantification of viral RNA and total HIV DNA in infected cells, the CM pictures suggest that epithelial cells do not support a complete viral replication cycle: X4-tropic viruses are imported into the nucleus in a non-productive way, whereas R5-tropic viruses transit through the cytoplasm without replication and are preferentially transmitted to susceptible activated peripheral blood mononuclear cells. Within the limit of experiments conducted in vitro on a continued cell line, these results indicate that the epithelial mucosa may participate to the selection of HIV-1 strains at the mucosal level.

  15. Expanded syringe exchange programs and reduced HIV infection among new injection drug users in Tallinn, Estonia

    Science.gov (United States)

    2011-01-01

    Background Estonia has experienced an HIV epidemic among intravenous drug users (IDUs) with the highest per capita HIV prevalence in Eastern Europe. We assessed the effects of expanded syringe exchange programs (SEP) in the capital city, Tallinn, which has an estimated 10,000 IDUs. Methods SEP implementation was monitored with data from the Estonian National Institute for Health Development. Respondent driven sampling (RDS) interview surveys with HIV testing were conducted in Tallinn in 2005, 2007 and 2009 (involving 350, 350 and 327 IDUs respectively). HIV incidence among new injectors (those injecting for 80%), and young adults (mean ages 24 to 27 years). The proportion of new injectors decreased significantly over the years (from 21% in 2005 to 12% in 2009, p = 0.005). HIV prevalence among all respondents stabilized at slightly over 50% (54% in 2005, 55% in 2007, 51% in 2009), and decreased among new injectors (34% in 2005, 16% in 2009, p = 0.046). Estimated HIV incidence among new injectors decreased significantly from 18/100 person-years in 2005 and 21/100 person-years in 2007 to 9/100 person-years in 2009 (p = 0.026). Conclusions In Estonia, a transitional country, a decrease in the HIV prevalence among new injectors and in the numbers of people initiating injection drug use coincided with implementation of large-scale SEPs. Further reductions in HIV transmission among IDUs are still required. Provision of 70 or more syringes per IDU per year may be needed before significant reductions in HIV incidence occur. PMID:21718469

  16. HIV testing practices of South African township MSM in the era of expanded access to ART.

    Science.gov (United States)

    Sandfort, Theo G M; Knox, Justin; Collier, Kate L; Lane, Tim; Reddy, Vasu

    2015-03-01

    While men who have sex with men (MSM) in Africa are at high risk for HIV infection, few of those already infected know their status. Effectively promoting frequent HIV testing-of increasing importance with the expanding accessibility of antiretroviral treatment-requires an understanding of the testing practices in this population. To understand men's HIV testing practices, including their behavior, experiences, and perceptions, we conducted in-depth interviews with 81 black South African MSM (ages 20-39), purposively recruited from four townships. Many men in the sample had tested for HIV. While ever having tested seemed to facilitate repeat testing, men still expressed a high level of discomfort with testing. It was common to test after having engaged in risky behavior, thus increasing anxiety about testing that was already present. Fear that they might test HIV positive caused some men to avoid testing until they were clearly sick, and others to avoid testing completely. HIV testing may increase in this population if it becomes a routine practice, instead of being driven by anxiety-inducing incidents. Mobilization through social support might facilitate frequent testing while education about current treatment options is needed.

  17. Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Fischer, William [Los Alamos National Laboratory; Wallstrom, Timothy [Los Alamos National Laboratory

    2009-01-01

    An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.

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

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

  20. Expanding ART for treatment and prevention of HIV in South Africa: Estimated cost and cost-effectiveness 2011-2050

    NARCIS (Netherlands)

    R. Granich (Reuben); J.G. Kahn (James); R.L. Bennett (Robin); C.B. Holmes (Charles ); N. Garg (Navneet); C. Serenata (Celicia); M.L. Sabin (Miriam Lewis); C. Makhlouf-Obermeyer (Carla); C. de Filippo Mack (Christina); J.P. Williams (Jon); L. Jones (Louisa); C. Smyth (Caoimhe); K.A. Kutch (Kerry ); L. Ying-Ru (Lo); M. Vitoria (Marco); Y. Souteyrand (Yves); S. Crowley (Siobhan); E.L. Korenromp (Eline)

    2012-01-01

    textabstractBackground: Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. Methods: We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART

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

    Science.gov (United States)

    Beauparlant, David; Rusert, Peter; Magnus, Carsten; Kadelka, Claus; Weber, Jacqueline; Uhr, Therese; Zagordi, Osvaldo; Oberle, Corinna; Duenas-Decamp, Maria J; Clapham, Paul R; Metzner, Karin J; Günthard, Huldrych F; Trkola, Alexandra

    2017-03-01

    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.

  2. 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.

  3. Health and Federal Budgetary Effects of Increasing Access to Antiretroviral Medications for HIV by Expanding Medicaid

    Science.gov (United States)

    Kahn, James G.; Haile, Brain; Kates, Jennifer; Chang, Sophia

    2001-01-01

    Objectives. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. Methods. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10 000, absent or inadequate medication insurance, and annual income less than $10 000. Two benefits were modeled, “full” and “limited” (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. Results. An estimated 38 000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13 000 AIDS diagnoses and 2600 deaths and add 5816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Conclusions. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs. PMID:11527783

  4. Health and federal budgetary effects of increasing access to antiretroviral medications for HIV by expanding Medicaid.

    Science.gov (United States)

    Kahn, J G; Haile, B; Kates, J; Chang, S

    2001-09-01

    OBJECTIVES. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10,000, absent or inadequate medication insurance, and annual income less than $10,000. Two benefits were modeled, "full" and "limited" (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. An estimated 38,000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13,000 AIDS diagnoses and 2600 deaths and add 5,816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.

  5. Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1: possible implications for sexual transmission of HIV-1.

    Directory of Open Access Journals (Sweden)

    Yuyang Tang

    Full Text Available The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call "natural pseudotyping," expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV, progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus.

  6. Infection of Female Primary Lower Genital Tract Epithelial Cells after Natural Pseudotyping of HIV-1: Possible Implications for Sexual Transmission of HIV-1

    Science.gov (United States)

    Tang, Yuyang; George, Alvin; Nouvet, Franklin; Sweet, Stephanie; Emeagwali, Nkiruka; Taylor, Harry E.; Simmons, Glenn; Hildreth, James E. K.

    2014-01-01

    The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call “natural pseudotyping,” expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus. PMID:25010677

  7. Ocular tropism of respiratory viruses.

    Science.gov (United States)

    Belser, Jessica A; Rota, Paul A; Tumpey, Terrence M

    2013-03-01

    Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.

  8. Tropism and pathogenicity of rickettsiae

    Directory of Open Access Journals (Sweden)

    Tsuneo eUchiyama

    2012-06-01

    Full Text Available Rickettsiae are obligate intracellular parasitic bacteria that cause febrile exanthematous illnesses such as Rocky Mountain spotted fever, Mediterranean spotted fever, epidemic and murine typhus, etc. Although the vector ranges of each Rickettsia species are rather restricted; i.e., ticks belonging to Arachnida and lice and fleas belonging to Insecta usually act as vectors for spotted fever group and typhus group rickettsiae, respectively, it would be interesting to elucidate the mechanisms controlling the vector tropism of rickettsiae. This review discusses the factors determining the vector tropism of rickettsiae. In brief, the vector tropism of rickettsiae species is basically consistent with their tropism towards cultured tick and insect cells. The mechanisms responsible for rickettsiae pathogenicity are also described. Recently, genomic analyses of rickettsiae have revealed that they possess several genes that are homologous to those affecting the pathogenicity of other bacteria. Analyses comparing the genomes of pathogenic and nonpathogenic strains of rickettsiae have detected many factors that are related to rickettsial pathogenicity. It is also known that a reduction in the rickettsial genome has occurred during the course of its evolution. Interestingly, Rickettsia species with small genomes, such as Rickettsia prowazekii, are more pathogenic to humans than those with larger genomes. This review also examines the growth kinetics of pathogenic and nonpathogenic species of spotted fever group rickettsiae in mammalian cells. The growth of nonpathogenic species is restricted in these cells, which is mediated, at least in part, by autophagy. The superinfection of nonpathogenic rickettsiae-infected cells with pathogenic rickettsiae results in an elevated yield of the nonpathogenic rickettsiae and the growth of the pathogenic rickettsiae. Autophagy is restricted in these cells. These results are discussed in this review.

  9. The Breadth of Expandable Memory CD8+ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

    Science.gov (United States)

    Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin; Mavrothalassitis, Orestes; Alvino, Donna Marie; Li, Jonathan Z.; Wilton, Shannon; Karel, Daniel; Piechocka-Trocha, Alicja; Chen, Huabiao; Pereyra, Florencia

    2015-01-01

    ABSTRACT Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the in vivo relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8+ T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P = 0.01) as well as treated progressors (P = 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P = 0.9 for Nef as determined by a Kruskal-Wallis test; P = 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r = −0.6; P = 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8+ T cell feature that would be desirable in a vaccine-induced T cell response. IMPORTANCE Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8+ T lymphocytes, is at least

  10. Expanding hospital HIV testing in the Bronx, New York and Washington, D.C.: Results from the HPTN 065 study.

    Science.gov (United States)

    Branson, Bernard M; Chavez, Pollyanna R; Hanscom, Brett; Greene, Elizabeth; McKinstry, Laura; Buchacz, Kate; Beauchamp, Geetha; Gamble, Theresa; Zingman, Barry S; Telzak, Edward; Naab, Tammey; Fitzpatrick, Lisa; El-Sadr, Wafaa M

    2017-11-27

    HIV testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington DC undertook various efforts to encourage staff to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. From February 1, 2011 to January 31, 2014, HIV tests were conducted during 6.5% of 1,621,016 ED visits and 13.0% of 361,745 inpatient admissions in Bronx hospitals and 13.8% of 729,172 ED visits and 22.0% of 150,655 inpatient admissions in DC, with wide variation by hospital. From year 1 to year 3, testing was stable in the Bronx (6.6% to 6.9% of ED visits, 13.0% to 13.6% of inpatient admissions), but increased in DC (11.9% to 15.8% of ED visits, 19.0% to 23.9% of inpatient admissions). Overall, in the Bronx 0.4% (408) of ED HIV tests were positive, 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive, 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive, 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient HIV tests were positive, 0.7% (189) were new diagnoses. Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

  11. Sensitive Cell-Based Assay for Determination of Human Immunodeficiency Virus Type 1 Coreceptor Tropism

    Czech Academy of Sciences Publication Activity Database

    Weber, Jan; Vazquez, A. C.; Winner, D.; Gibson, R. M.; Rhea, A. M.; Rose, J. D.; Wylie, D.; Henry, K.; Wright, A.; King, K.; Archer, J.; Poveda, E.; Soriano, V.; Robertson, D. L.; Olivo, P. D.; Arts, E. J.; Quinones-Mateu, M. E.

    2013-01-01

    Roč. 51, č. 5 (2013), s. 1517-1527 ISSN 0095-1137 Grant - others:NIH(US) P30 AI036219 Institutional support: RVO:61388963 Keywords : HIV tropism * phenotypic assay * genotypic prediction * disease progression * CCR5 antagonists * naive patients Subject RIV: EE - Microbiology, Virology Impact factor: 4.232, year: 2013

  12. Increases in Recent HIV Testing Among Men Who Have Sex With Men Coincide With the Centers for Disease Control and Prevention's Expanded Testing Initiative

    Science.gov (United States)

    Cooley, Laura A.; Wejnert, Cyprian; Rose, Charles E.; Paz-Bailey, Gabriela; Taussig, Jennifer; Gern, Robert; Hoyte, Tamika; Salazar, Laura; White, Jianglan; Todd, Jeff; Bautista, Greg; Flynn, Colin; Sifakis, Frangiscos; German, Danielle; Isenberg, Debbie; Driscoll, Maura; Hurwitz, Elizabeth; Doherty, Rose; Wittke, Chris; Prachand, Nikhil; Benbow, Nanette; Melville, Sharon; Pannala, Praveen; Yeager, Richard; Sayegh, Aaron; Dyer, Jim; Sheu, Shane; Novoa, Alicia; Thrun, Mark; Al-Tayyib, Alia; Wilmoth, Ralph; Higgins, Emily; Griffin, Vivian; Mokotoff, Eve; MacMaster, Karen; Wolverton, Marcia; Risser, Jan; Rehman, Hafeez; Padgett, Paige; Bingham, Trista; Sey, Ekow Kwa; LaLota, Marlene; Metsch, Lisa; Forrest, David; Beck, Dano; Cardenas, Gabriel; Nemeth, Chris; Anderson, Bridget J.; Watson, Carol-Ann; Smith, Lou; Robinson, William T.; Gruber, DeAnn; Barak, Narquis; Murrill, Chris; Neaigus, Alan; Jenness, Samuel; Hagan, Holly; Reilly, Kathleen H.; Wendel, Travis; Cross, Helene; Bolden, Barbara; D'Errico, Sally; Wogayehu, Afework; Godette, Henry; Brady, Kathleen A.; Kirkland, Althea; Sifferman, Andrea; Miguelino-Keasling, Vanessa; Velasco, Al; Tovar, Veronica; Raymond, H. Fisher; De León, Sandra Miranda; Rolón-Colón, Yadira; Marzan, Melissa; Courogen, Maria; Jaenicke, Tom; Thiede, Hanne; Burt, Richard; Jia, Yujiang; Opoku, Jenevieve; Sansone, Marie; West, Tiffany; Magnus, Manya; Kuo, Irene

    2015-01-01

    According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects. PMID:25352589

  13. Increases in Recent HIV Testing Among Men Who Have Sex With Men Coincide With the Centers for Disease Control and Prevention's Expanded Testing Initiative

    OpenAIRE

    Cooley, Laura A.; Wejnert, Cyprian; Rose, Charles E.; Paz-Bailey, Gabriela; Taussig, Jennifer; Gern, Robert; Hoyte, Tamika; Salazar, Laura; White, Jianglan; Todd, Jeff; Bautista, Greg; Flynn, Colin; Sifakis, Frangiscos; German, Danielle; Isenberg, Debbie

    2014-01-01

    According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects.

  14. Expression of the activation antigen CD69 predicts functionality of in vitro expanded peripheral blood mononuclear cells (PBMC) from healthy donors and HIV-infected patients

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Ersbøll, A K

    1998-01-01

    Gene therapy for AIDS necessitates harvest and expansion of PBMC from HIV-infected patients. We expanded PBMC from healthy blood donors and HIV-infected patients for up to 14 days using four expansion protocols: 3 days of phytohaemagglutinin (PHA) stimulation, continuous PHA stimulation, 3 days...... cytometry. PBMC from healthy donors and HIV-infected patients were readily expanded. The best expansion was obtained using stimulation for 3 days. After expansion, functionality of PBMC measured as proliferative response was partly conserved. PBMC expanded with stimulation for 3 days exhibited more...... preserved functionality than PBMC stimulated continuously (P healthy donors expanded with PHA stimulation for 3 days...

  15. HIV: cell binding and entry

    National Research Council Canada - National Science Library

    Wilen, Craig B; Tilton, John C; Doms, Robert W

    2012-01-01

    The first step of the human immunodeficiency virus (HIV) replication cycle-binding and entry into the host cell-plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system...

  16. Lumbar Facet Tropism: A Comprehensive Review.

    Science.gov (United States)

    Alonso, Fernando; Kirkpatrick, Christina M; Jeong, William; Fisahn, Christian; Usman, Sameera; Rustagi, Tarush; Loukas, Marios; Chapman, Jens R; Oskouian, Rod J; Tubbs, R Shane

    2017-06-01

    Scattered reports exist in the medical literature regarding facet tropism. However, this finding has had mixed conclusions regarding its origin and impact on the normal spine. We performed a literature review of the anatomy, embryology, biomechanics, and pathology related to lumbar facet tropism. Facet tropism is most commonly found at L4-L5 vertebral segments and there is some evidence that this condition may lead to facet degenerative spondylolisthesis, intervertebral disc disease, and other degenerative conditions. Long-term analyses of patients are necessary to elucidate relationships between associated findings and facet tropism. In addition, a universally agreed definition that is more precise should be developed for future investigative studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050.

    Directory of Open Access Journals (Sweden)

    Reuben Granich

    Full Text Available Antiretroviral Treatment (ART significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm(3 (current practice, CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs, HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.Expanding ART to CD4 count <350 cells/mm(3 prevents an estimated 265,000 (17% and 1.3 million (15% new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45% and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.

  18. Expanding HIV testing efforts in concentrated epidemic settings: a population-based survey from rural Vietnam.

    Directory of Open Access Journals (Sweden)

    Anastasia Pharris

    Full Text Available BACKGROUND: To improve HIV prevention and care programs, it is important to understand the uptake of HIV testing and to identify population segments in need of increased HIV testing. This is particularly crucial in countries with concentrated HIV epidemics, where HIV prevalence continues to rise in the general population. This study analyzes determinants of HIV testing in a rural Vietnamese population in order to identify potential access barriers and areas for promoting HIV testing services. METHODS: A population-based cross-sectional survey of 1874 randomly sampled adults was linked to pregnancy, migration and economic cohort data from a demographic surveillance site (DSS. Multivariate logistic regression analysis was used to determine which factors were associated with having tested for HIV. RESULTS: The age-adjusted prevalence of ever-testing for HIV was 7.6%; however 79% of those who reported feeling at-risk of contracting HIV had never tested. In multivariate analysis, younger age (aOR 1.85, 95% CI 1.14-3.01, higher economic status (aOR 3.4, 95% CI 2.21-5.22, and semi-urban residence (aOR 2.37, 95% CI 1.53-3.66 were associated with having been tested for HIV. HIV testing rates did not differ between women of reproductive age who had recently been pregnant and those who had not. CONCLUSIONS: We found low testing uptake (6% among pregnant women despite an existing prevention of mother-to-child HIV testing policy, and lower-than-expected testing among persons who felt that they were at-risk of HIV. Poverty and residence in a more geographically remote location were associated with less HIV testing. In addition to current HIV testing strategies focusing on high-risk groups, we recommend targeting HIV testing in concentrated HIV epidemic settings to focus on a scaled-up provision of antenatal testing. Additional recommendations include removing financial and geographic access barriers to client-initiated testing, and encouraging provider

  19. Sexual behaviors and HIV/syphilis testing among transgender individuals in China: implications for expanding HIV testing services.

    Science.gov (United States)

    Best, John; Tang, Weiming; Zhang, Ye; Han, Larry; Liu, Fengying; Huang, Shujie; Yang, Bin; Wei, Chongyi; Tucker, Joseph D

    2015-05-01

    HIV and syphilis are disproportionately common among transgender individuals globally, yet few studies have investigated transgender HIV/syphilis risk and testing in low- and middle-income nations. We conducted an online survey of men who have sex with men (MSM) and transgender individuals to examine sexual behaviors and HIV/syphilis testing in China. We recruited MSM and transgender individuals from 2 major Chinese lesbian, gay, bisexual, and transgender Web platforms. χ Test and logistic regression were used to compare risk behaviors, HIV and syphilis testing history, and prevalence between transgender individuals and other MSM. Among the 1320 participants, 52 (3.9%) self-identified as transgender. Demographics, including education, employment, and marital status, were similar between both groups, whereas transgender individuals were older. Condomless anal intercourse rate was comparable between the groups. Transgender individuals were less likely to report ever testing for HIV (34.6% vs. 62.0%) and syphilis (15.7% vs. 31.2%) with adjusted odds ratios of 0.36 (95% confidence interval, 0.20-0.65) and 0.42 (95% confidence interval, 0.20-0.91), respectively. We found a trend toward a higher HIV prevalence among transgender individuals (11.1% vs. 5.7%, P = 0.12). Transgender individuals have suboptimal HIV and syphilis testing rates in China. Given the substantial risk behaviors and burden of HIV/STI in the general Chinese MSM population and a lack of knowledge about transgender individuals, enhanced HIV/syphilis testing programs for transgender individuals in China are needed.

  20. 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.

  1. Blastocystis tropism in the pig intestine

    Science.gov (United States)

    Blastocystis subtype 5, a subtype known to infect humans, was detected by molecular methods in the feces of 36 naturally infected market age pigs. At necropsy, 6 heavily infected pigs were selected to determine the tropism of the infection within the gastrointestinal tract. Because so little is know...

  2. Generation of recombinant adenovirus vectors with modified fibers for altering viral tropism.

    OpenAIRE

    Krasnykh, V N; Mikheeva, G V; Douglas, J T; Curiel, D.T.

    1996-01-01

    To expand the utility of recombinant adenovirus vectors for gene therapy applications, methods to alter native viral tropism to achieve cell-specific transduction would be beneficial. To this end, we are pursuing genetic methods to alter the cell recognition domain of the adenovirus fiber. To incorporate these modified fibers into mature virions, we have developed a method based on homologous DNA recombination between two plasmids. A fiber-deleted, propagation-defective rescue plasmid has bee...

  3. Expanding substance use treatment options for HIV prevention with Buprenorphine-Naloxone: HIV Prevention Trials Network 058 (HPTN 058)

    Science.gov (United States)

    Metzger, David S.; Donnell, Deborah; Celentano, David D.; Jackson, J. Brooks; Shao, Yiming; Aramrattana, Apinun; Wei, Liu; Fu, Liping; Ma, Jun; Lucas, Gregory M.; Chawarski, Marek; Ruan, Yuhua; Richardson, Paul; Shin, Katherine; Chen, Ray Y.; Sugarman, Jeremy; Dye, Bonnie J.; Rose, Scott M.; Beauchamp, Geetha; Burns, David N.

    2015-01-01

    Background Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited. Methods HPTN 058 was a randomized controlled trial designed to compare the impact of two medication assisted treatment (MAT) strategies on HIV incidence or death among opioid dependent people who inject drugs (PWID). HIV-negative opiate dependent PWID were recruited from four communities in Thailand and China with historically high prevalence of HIV among PWID. 1251 participants were randomly assigned to either; 1) a one year intervention consisting of two opportunities for a 15 day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling (Short Term Medication Assisted Treatment: ST-MAT) or, 2) thrice weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions (Long Term Medication Assisted Treatment: LT-MAT) followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact. Results While the study was stopped early due to lower than expected occurrence of the primary endpoints, sufficient data were available to assess the impact of the interventions on drug use and injection related risk behavior. At weeks 26, 22% of ST-MAT participants had negative urinalyses for opioids compared to 57% in the LT-MAT (p<0.001). Differences disappeared in the year following treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection related risk behaviors were significantly reduced in both groups following randomization. Conclusions Participants receiving BUP/NX three times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection related risk behavior. These data support

  4. Expanding access to HIV counselling and testing at schools – the ...

    African Journals Online (AJOL)

    South Africa's HIV epidemic disproportionately affects the youth.¹ The importance of knowing one's status via voluntary counselling and testing (VCT) is recognised as a key strategy in fighting the epidemic and is reflected in the National Strategic Plan (NSP),2 which has set targets of 70% of all adults knowing their status by ...

  5. AIDS vaccine for Asia Network (AVAN: expanding the regional role in developing HIV vaccines.

    Directory of Open Access Journals (Sweden)

    Stephen J Kent

    2010-09-01

    Full Text Available The HIV/AIDS pandemic continues to spread and an AIDS vaccine is urgently needed. Regional alliances and international collaborations can foster the development and evaluation of the next generation of AIDS vaccine candidates. The importance of coordinating and harmonizing efforts across regional alliances has become abundantly clear. We recently formed the AIDS Vaccine for Asia Network (AVAN to help facilitate the development of a regional AIDS vaccine strategy that accelerates research and development of an AIDS vaccine through government advocacy, improved coordination, and harmonization of research; develops clinical trial and manufacturing capacity; supports ethical and regulatory frameworks; and ensures community participation.

  6. Pharmacy staff characteristics associated with support for pharmacy-based HIV-testing in pharmacies participating in the New York State Expanded Access Syringe Exchange Program

    Science.gov (United States)

    Amesty, Silvia; Blaney, Shannon; Crawford, Natalie D.; Rivera, Alexis V.; Fuller, Crystal

    2013-01-01

    Objective To determine support of in-pharmacy HIV-testing among pharmacy staff and the individual-level characteristics associated with in-pharmacy HIV testing support. Design Descriptive, nonexperimental, cross-sectional study. Setting New York City (NYC) during January 2008 to March 2009. Intervention 131 pharmacies registered in the Expanded Syringe Access Program (ESAP) completed a survey. Participants 480 pharmacy staff, including pharmacists, owners/managers, and technicians/clerks. Main outcome measures Support of in-pharmacy HIV testing. Results Support of in-pharmacy HIV testing is high among pharmacy staff (79.4%). Pharmacy staff that supported in-pharmacy vaccinations were significantly more likely to support in-pharmacy HIV testing. Pharmacy staff that think that selling syringes to IDUs causes the community to be littered with dirty syringes were significantly less likely to support in-pharmacy HIV testing. Conclusion Support for in-pharmacy HIV testing is high among our sample of ESAP pharmacy staff actively involved in non-prescription syringe sales. These findings suggest that active ESAP pharmacy staff may be amenable to providing HIV counseling and testing to injection drug users and warrants further investigation. PMID:22825227

  7. An end to perinatal HIV: success in the US requires ongoing and innovative efforts that should expand globally.

    Science.gov (United States)

    Burr, Carolyn K; Lampe, Margaret A; Corle, Sharron; Margolin, Frances S; Abresh, Chad; Clark, Jill

    2007-07-01

    The dramatic reduction of perinatally transmitted HIV in the United States has been a striking success story in the HIV epidemic. Routine HIV screening during pregnancy followed by appropriate therapy has been extremely effective. This paper puts forth three strategies needed to maintain these gains and reach the goal of eliminating perinatal HIV: standardize medical interventions and policy changes that support perinatal HIV reduction; institute HIV screening in routine preconception care to identify HIV infection in women before pregnancy; and critically focus attention and resources on primary prevention of HIV infection in women. Healthcare providers should incorporate HIV prevention education and routine screening into women's primary health care. Public health leaders should support and fund prevention strategies directed at young women. Successful approaches that have nearly eliminated perinatal HIV transmission in the United States offer valuable lessons that should be applied to primary HIV prevention for women in the United States and globally.

  8. Understanding and altering cell tropism of vesicular stomatitis virus

    Science.gov (United States)

    Hastie, Eric; Cataldi, Marcela; Marriott, Ian; Grdzelishvili, Valery Z.

    2013-01-01

    Vesicular stomatitis virus (VSV) is a prototypic nonsegmented negative-strand RNA virus. VSV’s broad cell tropism makes it a popular model virus for many basic research applications. In addition, a lack of preexisting human immunity against VSV, inherent oncotropism and other features make VSV a widely used platform for vaccine and oncolytic vectors. However, VSV’s neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe vector. Therefore, it is very important to understand the determinants of VSV tropism and develop strategies to alter it. VSV glycoprotein (G) and matrix (M) protein play major roles in its cell tropism. VSV G protein is responsible for VSV broad cell tropism and is often used for pseudotyping other viruses. VSV M affects cell tropism via evasion of antiviral responses, and M mutants can be used to limit cell tropism to cell types defective in interferon signaling. In addition, other VSV proteins and host proteins may function as determinants of VSV cell tropism. Various approaches have been successfully used to alter VSV tropism to benefit basic research and clinically relevant applications. PMID:23796410

  9. Understanding and altering cell tropism of vesicular stomatitis virus.

    Science.gov (United States)

    Hastie, Eric; Cataldi, Marcela; Marriott, Ian; Grdzelishvili, Valery Z

    2013-09-01

    Vesicular stomatitis virus (VSV) is a prototypic nonsegmented negative-strand RNA virus. VSV's broad cell tropism makes it a popular model virus for many basic research applications. In addition, a lack of preexisting human immunity against VSV, inherent oncotropism and other features make VSV a widely used platform for vaccine and oncolytic vectors. However, VSV's neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe vector. Therefore, it is very important to understand the determinants of VSV tropism and develop strategies to alter it. VSV glycoprotein (G) and matrix (M) protein play major roles in its cell tropism. VSV G protein is responsible for VSV broad cell tropism and is often used for pseudotyping other viruses. VSV M affects cell tropism via evasion of antiviral responses, and M mutants can be used to limit cell tropism to cell types defective in interferon signaling. In addition, other VSV proteins and host proteins may function as determinants of VSV cell tropism. Various approaches have been successfully used to alter VSV tropism to benefit basic research and clinically relevant applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Streamlining tasks and roles to expand treatment and care for HIV: randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    van Vuuren Cloete

    2008-04-01

    Full Text Available Abstract Background A major barrier to accessing free government-provided antiretroviral treatment (ART in South Africa is the shortage of suitably skilled health professionals. Current South African guidelines recommend that only doctors should prescribe ART, even though most primary care is provided by nurses. We have developed an effective method of educational outreach to primary care nurses in South Africa. Evidence is needed as to whether primary care nurses, with suitable training and managerial support, can initiate and continue to prescribe and monitor ART in the majority of ART-eligible adults. Methods/design This is a protocol for a pragmatic cluster randomised trial to evaluate the effectiveness of a complex intervention based on and supporting nurse-led antiretroviral treatment (ART for South African patients with HIV/AIDS, compared to current practice in which doctors are responsible for initiating ART and continuing prescribing. We will randomly allocate 31 primary care clinics in the Free State province to nurse-led or doctor-led ART. Two groups of patients aged 16 years and over will be included: a 7400 registering with the programme with CD4 counts of ≤ 350 cells/mL (mainly to evaluate treatment initiation and b 4900 already receiving ART (to evaluate ongoing treatment and monitoring. The primary outcomes will be time to death (in the first group and viral suppression (in the second group. Patients' survival, viral load and health status indicators will be measured at least 6-monthly for at least one year and up to 2 years, using an existing province-wide clinical database linked to the national death register. Trial registration Controlled Clinical Trials ISRCTN46836853

  11. A clinical and pharmacokinetic study of the combination of etravirine plus raltegravir in HIV patients with expanded intolerance or resistance

    Directory of Open Access Journals (Sweden)

    Sara Bañón

    2014-11-01

    Full Text Available Introduction: The combination of etravirine (ETR plus raltegravir (RAL could be an option for HIV patients with resistance, intolerance or important interactions with other drugs. However, there are few data on the efficacy, safety and pharmacokinetics of this dual therapy, taking into account the effect of HCV co-infection or the possible induction of ETR in the drug metabolism of RAL. Material and Methods: Cohort study of HIV patients initiating ETR plus RAL as dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least one month on therapy. Results: A total of 25 patients have been included in this combination since 2009. Mean age was 46 years, 72% were male, and 20 patients (80% had HCV co-infection (seven patients with fibrosis 3–4. Median nadir CD4+ count was 109 (60–209, and 21 patients had an HIV RNA level below 50 copies/mL. Median time on previous therapy was 473 months (IQR, 395–570, and reasons for this dual therapy was toxicity/intolerance in 19, and interactions in nine (two chemotherapy, three DAAs, two methadone, two other. After a median follow up of 722 days (473–1088: 53.3 patients-year, there were no cases of blips or virological failure. Six patients (24% discontinued therapy after more than 1.5 year on therapy, in four cases due to lost follow up and in two due to simplification after finishing the reason for interaction. There were no cases of liver toxicity, and only two patients increased slightly transaminases values (grade 1 and 2. Total cholesterol and triglycerides levels decrease significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from 185 to 143 mg/dL; p=0.01. CT/HDL ratio decreases from 4.35 to 4.28 after six months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40–249 and only one patient (6% was below the in vitro IC50 of the wild type. Conclusions: The combination of ETR plus RAL as dual therapy is effective and safe in patients with expanded

  12. Characterization of human papillomavirus type 154 and tissue tropism of gammapapillomaviruses.

    Science.gov (United States)

    Ure, Agustín Enrique; Forslund, Ola

    2014-01-01

    The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus.

  13. Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids.

    Science.gov (United States)

    Castle, Michael J; Turunen, Heikki T; Vandenberghe, Luk H; Wolfe, John H

    2016-01-01

    More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina.

  14. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

    Science.gov (United States)

    Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

    2012-01-01

    Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

  15. HTLV-1 and HIV-1 co-infection: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Carmen Isache

    2016-01-01

    HTLV and HIV share the same routes of transmission and the same tropism for T-lymphocytes. Co-infection occurs probably more frequently than we are aware, since testing for HTLV is not routinely performed in outpatient HIV clinics.

  16. Reorienting the HIV response in Niger toward sex work interventions: from better evidence to targeted and expanded practice.

    Science.gov (United States)

    Fraser, Nicole; Kerr, Cliff C; Harouna, Zakou; Alhousseini, Zeinabou; Cheikh, Nejma; Gray, Richard; Shattock, Andrew; Wilson, David P; Haacker, Markus; Shubber, Zara; Masaki, Emiko; Karamoko, Djibrilla; Görgens, Marelize

    2015-03-01

    Niger's low-burden, sex-work-driven HIV epidemic is situated in a context of high economic and demographic growth. Resource availability of HIV/AIDS has been decreasing recently. In 2007-2012, only 1% of HIV expenditure was for sex work interventions, but an estimated 37% of HIV incidence was directly linked to sex work in 2012. The Government of Niger requested assistance to determine an efficient allocation of its HIV resources and to strengthen HIV programming for sex workers. Optima, an integrated epidemiologic and optimization tool, was applied using local HIV epidemic, demographic, programmatic, expenditure, and cost data. A mathematical optimization algorithm was used to determine the best resource allocation for minimizing HIV incidence and disability-adjusted life years (DALYs) over 10 years. Efficient allocation of the available HIV resources, to minimize incidence and DALYs, would increase expenditure for sex work interventions from 1% to 4%-5%, almost double expenditure for antiretroviral treatment and for the prevention of mother-to-child transmission, and reduce expenditure for HIV programs focusing on the general population. Such an investment could prevent an additional 12% of new infections despite a budget of less than half of the 2012 reference year. Most averted infections would arise from increased funding for sex work interventions. This allocative efficiency analysis makes the case for increased investment in sex work interventions to minimize future HIV incidence and DALYs. Optimal HIV resource allocation combined with improved program implementation could have even greater HIV impact. Technical assistance is being provided to make the money invested in sex work programs work better and help Niger to achieve a cost-effective and sustainable HIV response.

  17. Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study.

    Science.gov (United States)

    Garcia, Federico; Poveda, Eva; Pérez-Elías, Maria Jesús; Quero, José Hernández; Ribas, Maria Angels; Martínez-Madrid, Onofre J; Flores, Juan; Crespo, Manel; Gutiérrez, Félix; García-Deltoro, Miguel; Imaz, Arkaitz; Ocampo, Antonio; Artero, Arturo; Blanco, Francisco; Bernal, Enrique; Pasquau, Juan; Mínguez-Gallego, Carlos; Pérez, Núria; Aiestarán, Aintzane; Paredes, Roger

    2014-01-01

    In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological

  18. Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

    Directory of Open Access Journals (Sweden)

    Federico Garcia

    2014-11-01

    Full Text Available Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1, initiation of Maraviroc (MVC plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910 carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL 10% in a singleton, initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week*100. Results: Tropism results were available from 141/175 (80.6% subjects screened: 87/141 (60% were R5 and 74/87 (85% were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm3 at screening, and median nadir CD4+ counts were 143 cells/mm3. Previous ART included PIs in 46 (62% subjects, NNRTIs in 27 (36% and integrase inhibitors (INIs in 1 (2%. The main reasons for treatment change were dyslipidemia (42%, gastrointestinal symptoms (22%, and liver toxicity (15%. MVC was given alongside TDF/FTC in 40 (54% subjects, ABC/3TC in 30 (40%, AZT/3TC in 2 (3% and ABC/TDF in 2 (3%. Sixty-two (84% subjects maintained VL<50 c/mL through week 48, whereas 12 (16% discontinued treatment: two (3% withdrew informed consent, one (1% had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1% was lost to follow-up, one (1% developed an ART-related adverse event (rash, two (3% died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36, and five (7% developed protocol

  19. Developing and Implementing Monitoring and Evaluation Methods in the New Era of Expanded Care and Treatment of HIV/AIDS

    Science.gov (United States)

    Wolf, R. Cameron; Bicego, George; Marconi, Katherine; Bessinger, Ruth; van Praag, Eric; Noriega-Minichiello, Shanti; Pappas, Gregory; Fronczak, Nancy; Peersman, Greet; Fiorentino, Renee K.; Rugg, Deborah; Novak, John

    2004-01-01

    The sharp rise in the HIV/AIDS burden worldwide has elicited calls for increased efforts to combat the spread and impact of HIV/AIDS. Efforts must continue with the aim to decrease new infections. At the same time, care and treatment services for those already infected can lead to longer, productive lives, thereby minimizing negative effects on…

  20. Expanding the role of community mobilization to accelerate progress towards ending vertical transmission of HIV in Uganda: the Networks model.

    Science.gov (United States)

    Mburu, Gitau; Iorpenda, Kate; Muwanga, Fred

    2012-07-11

    Efforts to prevent vertical transmission of HIV have gained momentum globally since the launch of the "Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive", reflecting the growing consensus that we now have low-cost, efficacious interventions that promise to end vertical transmission of HIV. Uganda is one of the 22 focus countries in the global plan and one of the 10 countries with the highest need for prevention of vertical transmission globally. In the context of current shortfalls in the prevention of vertical HIV transmission, this paper presents the results of the Networks project, a community mobilisation model implemented by the International HIV/AIDS Alliance in Uganda, and draws out the theoretical foundations and promising community mobilization practices relevant to prevention of vertical transmission. A retrospective review of the Network project's activities, documentation and evaluation was performed. The Networks project, through community mobilisation and greater involvement of people living with HIV, reached an estimated 1.3 million people with at least one health service. By clustering 750 groups of people living with HIV into larger coalitions, the project supported existing groups to amalgamate their collective strengths and skills in outreach, referral and literacy activities; and improved reach and coverage of HIV services through strengthened linkages with healthcare facilities. Our analysis of the Networks model shows that it could contribute to the prevention of vertical transmission of HIV as a replicable and sustainable community mobilisation approach. In particular, the Networks model increased the uptake of decentralized interventions for preventing vertical transmission through community referrals; promoted male involvement through peer sensitisation; and linked communities to advocacy channels for advancing maternal health and prevention of vertical HIV transmission. BY

  1. Expanding the prevention armamentarium portfolio: a framework for promoting HIV-Conversant Communities within a complex, adaptive epidemiological landscape.

    Science.gov (United States)

    Burman, Christopher J; Aphane, Marota; Mtapuri, Oliver; Delobelle, Peter

    2015-01-01

    The article describes a design journey that culminated in an HIV-Conversant Community Framework that is now being piloted in the Limpopo Province of South Africa. The objective of the initiative is to reduce the aggregate community viral load by building capacity at multiple scales that strengthens peoples' HIV-related navigational skill sets-while simultaneously opening a 'chronic situation' schema. The framework design is based upon a transdisciplinary methodological combination that synthesises ideas and constructs from complexity science and the management sciences as a vehicle through which to re-conceptualise HIV prevention. This resulted in a prototype that included the following constructs: managing HIV-prevention in a complex, adaptive epidemiological landscape; problematising and increasing the scope of the HIV knowledge armamentarium through education that focuses on the viral load and Langerhans cells; disruptive innovation and safe-fail probes followed by the facilitation of path creations and pattern management implementation techniques. These constructs are underpinned by a 'middle-ground' prevention approach which is designed to bridge the prevention 'fault line', enabling a multi-ontology conceptualisation of the challenge to be developed. The article concludes that stepping outside of the 'ordered' epistemological parameters of the existing prevention 'messaging' mind-set towards a more systemic approach that emphasises agency, structure and social practices as a contribution to 'ending AIDS by 2030' is worthy of further attention if communities are to engage more adaptively with the dynamic HIV landscape in South Africa.

  2. Identification of a large, fast-expanding HIV-1 subtype B transmission cluster among MSM in Valencia, Spain.

    Directory of Open Access Journals (Sweden)

    Juan Ángel Patiño-Galindo

    Full Text Available We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain. A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients. This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 113 patients, predominately men who have sex with men (MSM. Although it was significantly located in the city of Valencia (n = 105, phylogenetic analyses suggested this cluster derives from a larger HIV lineage affecting other Spanish localities (n = 194. Coalescent analyses estimated its expansion in Valencia to have started between 1998 and 2004. From 2004 to 2009, members of this cluster represented only 1.46% of the HIV-1 subtype B samples studied in Valencia (n = 5/143, whereas from 2010 onwards its prevalence raised to 12.64% (n = 100/791. In conclusion, we have detected a very large transmission cluster in the CV where it has experienced a very fast growth in the recent years in the city of Valencia, thus contributing significantly to the HIV epidemic in this locality. Its transmission efficiency evidences shortcomings in HIV control measures in Spain and particularly in Valencia.

  3. The 'Expanded HIV care in opioid substitution treatment' (EHOST) cluster-randomized, stepped-wedge trial: A study protocol.

    Science.gov (United States)

    Nosyk, B; Krebs, E; Min, J E; Ahamad, K; Buxton, J; Goldsmith, C; Hull, M; Joe, R; Krajden, M; Lima, V D; Olding, M; Wood, E; Montaner, J S G

    2015-11-01

    The public health response to HIV/AIDS has turned its focus onto optimizing health care system delivery to maximize case identification, access and sustained engagement in antiretroviral treatment (ART). Opioid Agonist Treatment (OAT) provides a critical opportunity for HIV testing and linkage to ART. The EHOST study is a cluster-randomized, stepped-wedge trial to evaluate a prescriber-focused intervention to increase HIV testing rates, and optimize ART engagement and retention outcomes among individuals engaged in OAT. The study will encompass all drug treatment clinics currently admitting patients for the treatment of opioid use disorder across the province of British Columbia, encompassing an estimated 90% of the OAT caseload. The trial will be executed over a 24-month period, with groups of clinics receiving the intervention in 6-month intervals. Evaluation of the proposed intervention's effectiveness will focus on three primary outcomes: (i) the HIV testing rate among those not known to be HIV positive; (ii) the rate of ART initiation among those not on ART; and (iii) the rate of ART continuation among those on ART. A difference-in-differences analytical framework will be applied to estimate the intervention's effect. This approach will assess site-specific changes in primary outcomes across clusters while adjusting for potential residual heterogeneity in patient case mix, volume, and quality of care across clinics. Statistical analysis of outcomes will be conducted entirely with linked population-level administrative health datasets. Facilitated by established collaborations between key stakeholders across the province, the EHOST intervention promises to optimize HIV testing and care within a marginalized and hard-to-reach population. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Expanding HIV testing and counselling into communities: Feasibility, acceptability, and effects of an integrated family planning/HTC service delivery model by Village Health Teams in Uganda.

    Science.gov (United States)

    Brunie, Aurélie; Wamala-Mucheri, Patricia; Akol, Angela; Mercer, Sarah; Chen, Mario

    2016-10-01

    Improving HIV testing and counselling (HTC) requires a range of strategies. This article reports on HTC service delivery by Village Health Teams (VHTs) in Uganda in the context of a model integrating this new component into pre-existing family planning services. Eight health centres from matched pairs were randomly allocated to intervention or control. After being trained, 36 VHTs reporting to selected facilities in the intervention group started offering HTC along with family planning, while VHTs in the control group provided family planning only. Proficiency testing was conducted as external quality assurance. A survey of all 36 VHTs and 137 family planning clients in the intervention group and 119 clients in the control group and a review of record data were conducted after 10 months. Survey responses by VHTs and their clients in the intervention group demonstrate knowledge of counselling messages and safe testing. External quality assessment results provide additional evidence of competency. Eighty per cent of the family planning clients surveyed in the intervention group received an HIV test during the intervention; 27% of those were first-time testers. More clients had ever tested for HIV in the intervention group compared with the control; clients also retested more often. Findings indicate that this model is feasible and acceptable for expanding quality HTC into communities. This study was registered with ClinicalTrials.gov, number [NCT02244398]. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic

    NARCIS (Netherlands)

    Urbanus, Anouk T.; van de Laar, Thijs J.; Stolte, Ineke G.; Schinkel, Janke; Heijman, Titia; Coutinho, Roel A.; Prins, Maria

    2009-01-01

    Background: Since 2000 outbreaks of sexually transmitted hepatitis C Virus (HCV) infections have been reported among HIV-infected men who have sex with men (MSM). We studied the prevalence and determinants of HCV-infection among MSM attending a large sexually transmitted infection (STI) clinic in

  6. The effective method for investigation meridian tropism theory in rats ...

    African Journals Online (AJOL)

    This present work describes an effective new method for study traditional Chinese medicine (TCM) on meridian tropism (MT) theory, which plays an essential role in clinical selection of TCM according to syndromes and strengthens the therapeutic effects. The new thread included material basis foundation and its tissue ...

  7. Human immature Langerhans cells restrict CXCR4-using HIV-1 transmission

    NARCIS (Netherlands)

    Sarrami-Forooshani, Ramin; Mesman, Annelies W.; van Teijlingen, Nienke H.; Sprokholt, Joris K.; van der Vlist, Michiel; Ribeiro, Carla M. S.; Geijtenbeek, Teunis B. H.

    2014-01-01

    Sexual transmission is the main route of HIV-1 infection and the CCR5-using (R5) HIV-1 is predominantly transmitted, even though CXCR4-using (X4) HIV-1 is often abundant in chronic HIV-1 patients. The mechanisms underlying this tropism selection are unclear. Mucosal Langerhans cells (LCs) are the

  8. Monocytes expand with immune dysregulation and is associated with insulin resistance in older individuals with chronic HIV.

    Directory of Open Access Journals (Sweden)

    Cecilia M Shikuma

    Full Text Available Rates of insulin resistance are increased in HIV-infected patients on stable antiretroviral therapy (ART. Such increase may partially be due to HIV-induced immune dysregulation involving monocytes (MO and its subsets.Cross-sectional analysis of 141 HIV-infected subjects age ≥ 40 years on stable ART. Homeostatic model assessment-insulin resistance (HOMA-IR and rates of metabolic syndrome were calculated. Subjects were classified by fasting glucose and oral glucose tolerance test (OGTT into clinical diabetes categories. Multi-parametric flow cytometry was used to determine MO subset percentages: [classical (CD14(++CD16(-, intermediate (CD14(++CD16(+, non-classical (CD14(low/+CD16(++, and a recently identified fourth (CD14(low/+CD16(- 'transitional' MO subset] and percentage of activated (CD38(+HLA-DR(+ CD8 T cells. Absolute levels of cells were calculated using clinical CBC and T cell subset data. Multiple plasma soluble biomarkers were assessed by Luminex technology.Median age 50 years, CD4 count (percent 505 cells/µL (29%, and 89% male. Total MO (r=-0.23, p=0.006 and classical and non-classical MO subsets correlated negatively with CD4 percent. No correlations were seen with CD4 count as absolute values. Log-total MO and log-classical MO predicted HOMA-IR independently of HIV immuno-virologic and diabetes risk factors (β=0.42, p=0.02 and β=0.35, p=0.02, respectively and were increased in subjects with metabolic syndrome (p=0.03 and p=0.05 respectively. Total and/or subset MO levels correlated with multiple soluble plasma biomarkers including CRP, IL-6, MMP-9, MPO, SAA, SAP and tPAI-1, with tPAI-1 independently predicting HOMA-IR (β=0.74, p<0.001.MO levels increase with worsening HIV immune dysregulation as assessed by CD4 percent. CD4 percent may provide additional information about MO and metabolic risk in this population beyond absolute values. MO, and specifically classical MO, may contribute to insulin resistance and metabolic syndrome

  9. Expanding the generation and use of economic and financial data to improve HIV program planning and efficiency: a global perspective.

    Science.gov (United States)

    Holmes, Charles B; Atun, Rifat; Avila, Carlos; Blandford, John M

    2011-08-01

    Cost information is needed at multiple levels of health care systems to inform the public health response to HIV. To date, most attention has been paid to identifying the cost drivers of providing antiretroviral treatment, and these data have driven interventions that have been successful in reducing drug and human resource costs. The need for further cost information, especially for less well-studied areas such as HIV prevention, is particularly acute given global budget constraints and ongoing efforts to extract the greatest possible value from money spent on the response. Cost information can be collected from multiple perspectives and levels of the health care system (site, program, and national levels), and it is critical to choose the appropriate methodology in order to generate the appropriate information for decision-making. Organizations such as United States President's Emergency Plan for AIDS Relief, the Global Fund to Fight AIDS, Tuberculosis, and Malaria, and other organizations are working together to bridge the divide between the fields of economics and HIV program implementation by accelerating the collection of cost data and building further local demand and capacity for their use.

  10. Induction of Robust Immune Responses against Human Immunodeficiency Virus Is Supported by the Inherent Tropism of Adeno-Associated Virus Type 5 for Dendritic Cells▿

    OpenAIRE

    Xin, Ke-Qin; MIZUKAMI, HIROAKI; Urabe, Masashi; Toda, Yoshihiko; Shinoda, Kaori; Yoshida, Atsushi; Oomura, Kenji; Kojima, Yoshitsugu; Ichino, Motohide; Klinman, Dennis; Ozawa, Keiya; Okuda, Kenji

    2006-01-01

    The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study o...

  11. Understanding and altering cell tropism of vesicular stomatitis virus

    OpenAIRE

    Hastie, Eric; Cataldi, Marcela; Marriott, Ian; Valery Z Grdzelishvili

    2013-01-01

    Vesicular stomatitis virus (VSV) is a prototypic nonsegmented negative-strand RNA virus. VSV’s broad cell tropism makes it a popular model virus for many basic research applications. In addition, a lack of preexisting human immunity against VSV, inherent oncotropism and other features make VSV a widely used platform for vaccine and oncolytic vectors. However, VSV’s neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a sa...

  12. Chinese highly pathogenic porcine reproductive and respiratory syndrome virus exhibits more extensive tissue tropism for pigs

    Directory of Open Access Journals (Sweden)

    Li Limin

    2012-09-01

    Full Text Available Abstract Background The highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV emerging in China exhibits high fatality to pigs. However, the mechanism related to the increased pathogenicity of the virus remains unclear. In the present study, the differences in tissue tropism between the highly pathogenic PRRSV strain (JXwn06 and the low pathogenic PRRSV strain (HB-1/3.9 were investigated using PRRSV-specific immunohistochemistry (IHC staining to provide evidence for elucidating possible mechanism of the pathogenicity of Chinese highly pathogenic PRRSV. Findings IHC examination showed that PRRSV antigen in the tissues including spleen, tonsil, thymus, kidney, cerebellum, stomach, small intestine, large intestine, turbinal bone and laryngeal cartilage was positive in more pigs inoculated with JXwn06 than HB-1/3.9, and the tissues including trachea, esophagus, liver, mandibular gland and thyroid gland were positive for viral antigen in the pigs inoculated with JXwn06, but not in the pigs inoculated with HB-1/3.9. Meanwhile, we observed that epithelium in tissues including interlobular bile duct in liver, distal renal tubule of kidney, esophageal gland and tracheal gland were positive for viral antigen only in JXwn06-inoculated pigs, and epithelium of gastric mucosa and fundic gland, and intestinal gland were positive for viral antigen in both JXwn06- and HB-1/3.9-inoculated pigs, using monoclonal antibodies to N and Nsp2 proteins. Conclusions Taken together, these findings indicate that the highly pathogenic PRRSV JXwn06 displays an expanded tissue tropism in vivo, suggesting this may contribute to its high pathogenicity to pigs.

  13. A mosaic adenovirus possessing serotype Ad5 and serotype Ad3 knobs exhibits expanded tropism

    NARCIS (Netherlands)

    Takayama, K; Reynolds, PN; Short, JS; Kawakami, Y; Adachi, Y; Glasgow, JN; Rots, MG; Krasnykh, VN; Douglas, JT; Curiel, DT

    2003-01-01

    The efficiency of cancer gene therapy with recombinant adenoviruses based on serotype 5 (Ad5) has been limited partly because of variable, and often low, expression by human primary cancer cells of the primary cellular-receptor which recognizes the knob domain of the fiber protein, the coxsackie and

  14. HIV

    African Journals Online (AJOL)

    Introduction. The·human immunodeficiency virus (HIV) can be transmiHed from one person to onother through the use of non-sterile nee- dles, syringes, and other skin-piercing and invasive instruments. Proper .sterilization of all such instruments is therefore important to prevent its transmission. HIV is very sensitive to ...

  15. hiv

    African Journals Online (AJOL)

    2016-03-31

    Mar 31, 2016 ... Indexed By: African Journal Online (AJOL); Texila American University; Genamics; Scholarsteer; EIJASR; CAS-American Chemical. Society; and IRMS Informatics India (J-Gate). ABSTRACT. This study evaluated the effect of HIV infection on CD4 T-lymphocyte depletion in people living with HIV/AIDS.

  16. Development and Applications of VSV Vectors Based on Cell Tropism.

    Science.gov (United States)

    Tani, Hideki; Morikawa, Shigeru; Matsuura, Yoshiharu

    2011-01-01

    Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency are useful tools not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV) is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own envelope (G) gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses. These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors. Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities. Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.

  17. An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3'-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients.

    Science.gov (United States)

    Swart, Marelize; Evans, Jonathan; Skelton, Michelle; Castel, Sandra; Wiesner, Lubbe; Smith, Peter J; Dandara, Collet

    2015-01-01

    Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy (HAART) in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in plasma concentrations has been reported. Poor treatment outcomes such as development of adverse drug reactions or treatment failure have been linked to EFV plasma concentrations outside the therapeutic range (1-4 μg/mL) in some studies. The drug metabolizing enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP1A2, CYP2A6, CYP3A4, CYP3A5, and UGT2B7. DME coding genes are also regulated by microRNAs through targeting the 3'-untranslated region. Expanded analysis of 30 single nucleotide polymorphisms (SNPs), including those in the 3'-UTR, was performed to identify pharmacogenetics determinants of EFV plasma concentrations in addition to CYP2B6 c.516G>T and c.983T>C SNPs. SNPs in CYP1A2, CYP2B6, UGT2B7, and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV. Despite evaluating thirty SNPs, CYP2B6 c.516G>T and c.983T>C SNPs remain the most prominent predictors of EFV plasma concentration. We have shown that CYP2B6 c.516G>T and c.983T>C SNPs are the most important predictors of EFV plasma concentration after taking into account all other SNPs, including genetic variation in the 3'-UTR, and variables affecting EFV metabolism.

  18. Glycated AAV vectors: chemical redirection of viral tissue tropism.

    Science.gov (United States)

    Horowitz, Eric D; Weinberg, Marc S; Asokan, Aravind

    2011-04-20

    A chemical approach for selective masking of arginine residues on viral capsids featuring an exogenous glycation reaction has been developed. Reaction of adeno-associated viral (AAV) capsids with the α-dicarbonyl compound, methylglyoxal, resulted in formation of arginine adducts. Specifically, surface-exposed guanidinium side chains were modified into charge neutral hydroimidazolones, thereby disrupting a continuous cluster of basic amino acid residues implicated in heparan sulfate binding. Consequent loss in heparin binding ability and decrease in infectivity were observed. Strikingly, glycated AAV retained the ability to infect neurons in the mouse brain and were redirected from liver to skeletal and cardiac muscle following systemic administration in mice. Further, glycated AAV displayed altered antigenicity demonstrating the potential for evading antibody neutralization. Generation of unnatural amino acid side chains through capsid glycation might serve as an orthogonal strategy to engineer AAV vectors displaying novel tissue tropisms for gene therapy applications.

  19. Migration and Tissue Tropism of Innate Lymphoid Cells

    Science.gov (United States)

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  20. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis

    Science.gov (United States)

    Millet, Jean Kaoru; Whittaker, Gary R.

    2015-01-01

    Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity. PMID:25445340

  1. Relationship between facet tropism and facet joint degeneration in the sub-axial cervical spine

    Directory of Open Access Journals (Sweden)

    Xin Rong

    2017-02-01

    Full Text Available Abstract Background Facet tropism is the angular asymmetry between the left and right facet joint orientation. Although debatable, facet tropism was suggested to be associated with disc degeneration, facet degeneration and degenerative spondylolisthesis in the lumbar spine. The purpose of this study was to explore the relationship between facet tropism and facet degeneration in the sub-axial cervical spine. Methods A total of 200 patients with cervical spondylosis were retrospectively analyzed. Facet degeneration was categorized into 4 grade: grade I, normal; grade II, degenerative changes including joint space narrowing, cyst formation, small osteophytes (3 mm without fusion of the joint; grade IV, bony fusion of the facet joints. Facet orientations and facet tropisms with respect to the transverse, sagittal and coronal plane were calculated from the reconstructed cervical spine, which was based on the axial CT scan images. The paired facet joints were then categorized into three types: symmetric, moderated tropism and severe tropism. Univariate and multivariate analysis were performed to evaluate the relationship between any demographic and anatomical factor and facet degeneration. Results The mean age of enrolled patients was 46.23 years old (ranging from 30 to 64 years old. There were 114 males and 86 females. The degrees of facet degeneration varied according to cervical levels and ages. Degenerated facet joints were most common at C2-C3 level and more common in patients above 50 years old. The facet orientations were also different from level to level. By univariate analysis, genders, ages, cervical levels, facet orientations and facet tropisms were all significantly different between the normal facets and degenerated facets. However, results from multivariate logistic regression suggested only age and facet tropism with respect to the sagittal plane were related to facet degeneration. Conclusion Facet degeneration were more common at

  2. The case for expanding the definition of 'key populations' to include high-risk groups in the general population to improve targeted HIV prevention efforts.

    Science.gov (United States)

    Shisana, Olive; Zungu, N; Evans, M; Risher, K; Rehle, T; Clementano, D

    2015-09-22

    Two additional key populations within the general population in South Africa (SA) that are at risk of HIV infection are black African women aged 20 - 34 years and black African men aged 25 - 49 years. To investigate the social determinants of HIV serostatus for these two high-risk populations. Data from the 2012 South African National HIV Prevalence, Incidence, and Behaviour Survey were analysed for black African women aged 20 - 34 years and black African men aged 25 - 49 years. Of the 6.4 million people living with HIV in SA in 2012, 1.8 million (28%) were black women aged 20 - 34 years and 1.9 million (30%) black men aged 25 - 49 years. In 2012, they constituted 58% of the total HIV-positive population and 48% of the newly infected population. Low socioeconomic status (SES) was strongly associated (p<0.001) with being HIV-positive among black women aged 20 - 34 years, and was marginally significant among black men aged 25 - 49 years (p<0.1). Low SES is a critical social determinant for HIV infection among the high-risk groups of black African women aged 20 - 34 years and black African men aged 25 - 49 years. Targeted interventions for these key populations should prioritise socioeconomic empowerment, access to formal housing and services, access to higher education, and broad economic transformation.

  3. Differential Cellular Tropism of Lentivirus and Adeno-Associated Virus in the Brain of Cynomolgus Monkey

    OpenAIRE

    An, Heeyoung; Cho, Doo-Wan; Lee, Seung Eun; Yang, Young-Su; Han, Su-Cheol; Lee, C. Justin

    2016-01-01

    Many researchers are using viruses to deliver genes of interest into the brains of laboratory animals. However, certain target brain cells are not easily infected by viruses. Moreover, the differential tropism of different viruses in monkey brain is not well established. We investigated the cellular tropism of lentivirus and adeno-associated virus (AAV) toward neuron and glia in the brain of cynomolgus monkeys (Macaca fascularis). Lentivirus and AAV were injected into putamen of the monkey br...

  4. Breaking Barriers to an AIDS Model with Macaque-Tropic HIV-1 Derivatives

    OpenAIRE

    Kimata, Jason T; Hongmei Ruan; Rajesh Thippeshappa

    2012-01-01

    The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as...

  5. Induction of Robust Immune Responses against Human Immunodeficiency Virus Is Supported by the Inherent Tropism of Adeno-Associated Virus Type 5 for Dendritic Cells▿

    Science.gov (United States)

    Xin, Ke-Qin; Mizukami, Hiroaki; Urabe, Masashi; Toda, Yoshihiko; Shinoda, Kaori; Yoshida, Atsushi; Oomura, Kenji; Kojima, Yoshitsugu; Ichino, Motohide; Klinman, Dennis; Ozawa, Keiya; Okuda, Kenji

    2006-01-01

    The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy. PMID:17005662

  6. Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells.

    Science.gov (United States)

    Xin, Ke-Qin; Mizukami, Hiroaki; Urabe, Masashi; Toda, Yoshihiko; Shinoda, Kaori; Yoshida, Atsushi; Oomura, Kenji; Kojima, Yoshitsugu; Ichino, Motohide; Klinman, Dennis; Ozawa, Keiya; Okuda, Kenji

    2006-12-01

    The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.

  7. Expanding Access to HIV Viral Load Testing: A Systematic Review of RNA Stability in EDTA Tubes and PPT beyond Current Time and Temperature Thresholds: e113813

    National Research Council Canada - National Science Library

    Kimberly Bonner; Reed A Siemieniuk; Andrew Boozary; Teri Roberts; Emmanuel Fajardo; Jennifer Cohn

    2014-01-01

    .... Methods and Findings Using a pre-defined protocol, five databases were searched for studies where blood samples from HIV patients were stored at time and temperature points that exceeded manufacturer recommendations...

  8. Basic HIV/AIDS Statistics

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Center . Expand All Collapse All How many new HIV infections are there each year in the United ...

  9. Recent Observations on Australian Bat Lyssavirus Tropism and Viral Entry

    Directory of Open Access Journals (Sweden)

    Dawn L. Weir

    2014-02-01

    Full Text Available Australian bat lyssavirus (ABLV is a recently emerged rhabdovirus of the genus lyssavirus considered endemic in Australian bat populations that causes a neurological disease in people indistinguishable from clinical rabies. There are two distinct variants of ABLV, one that circulates in frugivorous bats (genus Pteropus and the other in insectivorous microbats (genus Saccolaimus. Three fatal human cases of ABLV infection have been reported, the most recent in 2013, and each manifested as acute encephalitis but with variable incubation periods. Importantly, two equine cases also arose recently in 2013, the first occurrence of ABLV in a species other than bats or humans. Similar to other rhabdoviruses, ABLV infects host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion facilitated by its single fusogenic envelope glycoprotein (G. Recent studies have revealed that proposed rabies virus (RABV receptors are not sufficient to permit ABLV entry into host cells and that the unknown receptor is broadly conserved among mammalian species. However, despite clear tropism differences between ABLV and RABV, the two viruses appear to utilize similar endocytic entry pathways. The recent human and horse infections highlight the importance of continued Australian public health awareness of this emerging pathogen.

  10. Spaceflight studies of tropisms in the European Modular Cultivation System

    Science.gov (United States)

    Kiss, J. Z.; Correll, M. J.; Edelmann, R. E.

    Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μ g, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station (ISS), we have been performing ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments that will use Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue-light and red-light signaling systems interact with each other, and also with the gravisensing system.

  11. Operations of a spaceflight experiment to investigate plant tropisms

    Science.gov (United States)

    Kiss, John Z.; Kumar, Prem; Millar, Katherine D. L.; Edelmann, Richard E.; Correll, Melanie J.

    2009-10-01

    Plants will be an important component in bioregenerative systems for long-term missions to the Moon and Mars. Since gravity is reduced both on the Moon and Mars, studies that identify the basic mechanisms of plant growth and development in altered gravity are required to ensure successful plant production on these space colonization missions. To address these issues, we have developed a project on the International Space Station (ISS) to study the interaction between gravitropism and phototropism in Arabidopsis thaliana. These experiments were termed TROPI (for tropisms) and were performed on the European Modular Cultivation System (EMCS) in 2006. In this paper, we provide an operational summary of TROPI and preliminary results on studies of tropistic curvature of seedlings grown in space. Seed germination in TROPI was lower compared to previous space experiments, and this was likely due to extended storage in hardware for up to 8 months. Video downlinks provided an important quality check on the automated experimental time line that also was monitored with telemetry. Good quality images of seedlings were obtained, but the use of analog video tapes resulted in delays in image processing and analysis procedures. Seedlings that germinated exhibited robust phototropic curvature. Frozen plant samples were returned on three space shuttle missions, and improvements in cold stowage and handing procedures in the second and third missions resulted in quality RNA extracted from the seedlings that was used in subsequent microarray analyses. While the TROPI experiment had technical and logistical difficulties, most of the procedures worked well due to refinement during the project.

  12. The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls

    Science.gov (United States)

    Imamichi, Hiromi; Lempicki, Richard A.; Adelsberger, Joseph W.; Hasley, Rebecca B.; Rosenberg, Alice; Roby, Gregg; Rehm, Catherine A.; Nelson, Amy; Krishnan, Sonya; Pavlick, Mark; Woods, Christian J.; Baseler, Michael W.; Lane, H. Clifford

    2013-01-01

    HIV-induced immune activation leads to expansion of a subset of human CD8+ T cells expressing HLA-DR antigens. Expansion of CD8+HLA-DR+ T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent “immune exhaustion” and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR-engagement. Detailed cell cycle analysis revealed that compared with their CD8+HLA-DR-counterpart, the CD8+HLA-DR+ T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8+ pool of cells in vivo that undergo further expansion independent of ongoing TCR-engagement. No qualitative differences were noted between CD8+HLA-DR+ cells from HIV+ and HIV− donors, indicating that the generation of CD8+HLA-DR+ T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection. PMID:22777759

  13. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  14. Expander Codes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 1. Expander Codes - The Sipser–Spielman Construction. Priti Shankar. General Article Volume 10 ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science Bangalore 560 012, India.

  15. The expanding role of civil society in the global HIV/AIDS response: what has the President's Emergency Program For AIDS Relief's role been?

    Science.gov (United States)

    Coutinho, Alex; Roxo, Uchechi; Epino, Henry; Muganzi, Alex; Dorward, Emily; Pick, Billy

    2012-08-15

    Civil society has been part of the HIV/AIDS response from the very beginning of the epidemic, often becoming engaged before national governments. Traditional roles of civil society--advocacy, activism, serving as government watchdog, and acting as community caretaker--have been critical to the response. In addition, civil society organizations (CSOs) play an integral part in providing world-class HIV prevention and treatment services and helping to ensure continuity of care. The President's Emergency Program for AIDS Relief (PEPFAR) has significantly increased the global scale-up of combination antiretroviral therapy reaching for more than 5 million people in developing countries, as well as implementation of effective evidence-based combination prevention approaches. PEPFAR databases in 5 countries and annual reports from a centrally managed initiative were mined and analyzed to determine the numbers and types of CSOs funded by PEPFAR over a 5-year period (2006-2011). Data are also presented from Uganda showing the overall resource growth in CSO working for HIV. Case studies document the evolution of 3 indigenous CSOs that increased the capacity to implement activities with PEPFAR funding. A legacy of PEPFAR has been the growth of civil society to address social and health issues as well as recognition by governments that partnerships with beneficiaries and civil society result in better outcomes. Scale-up of the global response could not have happened without the involvement of civil society and people living with HIV. This game changing partnership to jointly tackle the problems that countries face may well be the greatest benefit emerging from the HIV epidemic.

  16. Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing.

    Science.gov (United States)

    Goedert, James J; Swenson, Luke C; Napolitano, Laura A; Haddad, Mojgan; Anastos, Kathryn; Minkoff, Howard; Young, Mary; Levine, Alexandra; Adeyemi, Oluwatoyin; Seaberg, Eric C; Aouizerat, Bradley; Rabkin, Charles S; Harrigan, P Richard; Hessol, Nancy A

    2015-01-01

    Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P values and conditional logistic regression. In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 0.56-0.81). Concordance was similar among cases and controls. HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer.

  17. CDC Vital Signs: HIV Care Saves Lives

    Science.gov (United States)

    ... in HIV medical care. Health departments and communitybased organizations can Expand HIV testing services to get people ... Diseases (STDs) CDC Global HIV/AIDS CDC Lesbian, Gay, Bisexual, and Transgender Health Preventing Chronic Disease On ...

  18. Differential tropism in roots and shoots infected by Citrus tristeza virus.

    Science.gov (United States)

    Harper, S J; Cowell, S J; Robertson, C J; Dawson, W O

    2014-07-01

    Virus tropism is a result of interactions between virus, host and vector species, and determines the fate of an infection. In this study, we examined the infection process of Citrus tristeza virus (CTV) in susceptible and resistant species, and found that the tropism of CTV is not simply phloem limited, but tissue specific. In resistant species, virus infection was not prevented, but mostly restricted to the roots. This phenomenon was also observed after partial replacement of genes of one CTV strain from another, despite both parental strains being capable of systemic infection. Finally, the roots remained susceptible in the absence of viral gene products needed for systemic infection of shoots. Our results suggest that all phloem cells within a plant are not equally susceptible and that changes in host or virus may produce a novel tropism: restriction by the host to a location where further virus spread is prevented. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Partition expanders

    Czech Academy of Sciences Publication Activity Database

    Gavinsky, Dmitry; Pudlák, Pavel

    2017-01-01

    Roč. 60, č. 3 (2017), s. 378-395 ISSN 1432-4350 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : expanders * pseudorandomness * communication complexity Subject RIV: BA - General Mathematics Impact factor: 0.645, year: 2016 http://link.springer.com/article/10.1007%2Fs00224-016-9738-5

  20. Tuberculosis and tuberculosis/HIV/AIDS-associated mortality in Africa: the urgent need to expand and invest in routine and research autopsies.

    Science.gov (United States)

    Mudenda, Victor; Lucas, Sebastian; Shibemba, Aaron; O'Grady, Justin; Bates, Matthew; Kapata, Nathan; Schwank, Samana; Mwaba, Peter; Atun, Rifat; Hoelscher, Michael; Maeurer, Markus; Zumla, Alimuddin

    2012-05-15

    Frequently quoted statistics that tuberculosis and human immunodeficiency virus (HIV)/AIDS are the most important infectious causes of death in high-burden countries are based on clinical records, death certificates, and verbal autopsy studies. Causes of death ascertained through these methods are known to be grossly inaccurate. Most data from Africa on mortality and causes of death currently used by international agencies have come from verbal autopsy studies, which only provide inaccurate estimates of causes of death. Autopsy rates in most sub-Saharan African countries have declined over the years, and actual causes of deaths in the community and in hospitals in most sub-Saharan African countries remain unknown. The quality of cause-specific mortality statistics remains poor. The effect of various interventions to reduce mortality rates can only be evaluated accurately if cause-specific mortality data are available. Autopsy studies could have particular relevance to direct public health interventions, such as vaccination programs or preventive therapy, and could also allow for study of background levels of subclinical tuberculosis disease, Mycobacterium tuberculosis-HIV coinfection, and other infectious and noncommunicable diseases not yet clinically manifest. Autopsies performed soon after death may represent a unique opportunity to understand the pathogenesis of M. tuberculosis and the pathogenesis of early deaths after initiation of antiretroviral therapy. The few autopsies performed so far for research purposes have yielded invaluable information and insights into tuberculosis, HIV/AIDS, and other opportunistic infections. Accurate cause-specific mortality data are essential for prioritization of governmental and donor investments into health services to reduce morbidity and mortality from deadly infectious diseases such as tuberculosis and HIV/AIDS. There is an urgent need for reviving routine and research autopsies in sub-Saharan African countries.

  1. Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: evidence for local spread among MSMs in Bucharest area.

    Science.gov (United States)

    Paraschiv, Simona; Otelea, Dan; Batan, Ionelia; Baicus, Cristian; Magiorkinis, Gkikas; Paraskevis, Dimitrios

    2012-07-01

    HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003-2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. 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.

  3. Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells▿

    OpenAIRE

    Stanford, Marianne M.; Barrett, John W.; Nazarian, Steven H.; Werden, Steven; McFadden, Grant

    2006-01-01

    Myxoma virus is a rabbit-specific poxvirus pathogen that also exhibits a unique tropism for human tumor cells and is dramatically oncolytic for human cancer xenografts. Most tumor cell lines tested are permissive for myxoma infection in a fashion intimately tied to the activation state of Akt kinase. A host range factor of myxoma virus, M-T5, directly interacts with Akt and mediates myxoma virus tumor cell tropism. mTOR is a regulator of cell growth and metabolism downstream of Akt and is spe...

  4. Expanding versus non expanding universe

    CERN Document Server

    Alfonso-Faus, Antonio

    2012-01-01

    In cosmology the number of scientists using the framework of an expanding universe is very high. This model, the big-bang, is now overwhelmingly present in almost all aspects of society. It is the main stream cosmology of today. A small number of scientists are researching on the possibility of a non-expanding universe. The existence of these two groups, one very large and the other very small, is a good proof of the use of the scientific method: it does not drive to an absolute certainty. All models have to be permanently validated, falsified. Ockham's razor, a powerful philosophical tool, will probably change the amount of scientists working in each of these groups. We present here a model where a big-bang is unnecessary. It ends, in a finite time, in a second INFLATION, or a disaggregation to infinity. We also discuss the possibilities of a non-expanding universe model. Only a few references will be cited, mainly concerned with our own work in the past, thus purposely avoiding citing the many thousands of ...

  5. Linking Influenza Virus Tissue Tropism to Population-Level Reproductive Fitness

    NARCIS (Netherlands)

    L.A. Reperant (Leslie); T. Kuiken (Thijs); B.T. Grenfell (Bryan); A.D.M.E. Osterhaus (Albert); A.P. Dobson (Andrew)

    2012-01-01

    textabstractInfluenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of

  6. Evolution of HIV-1 coreceptor usage and coreceptor switching during pregnancy.

    Science.gov (United States)

    Ransy, Doris G; Motorina, Alena; Merindol, Natacha; Akouamba, Bertine S; Samson, Johanne; Lie, Yolanda; Napolitano, Laura A; Lapointe, Normand; Boucher, Marc; Soudeyns, Hugo

    2014-03-01

    Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. To document the evolution of coreceptor tropism during pregnancy, a longitudinal study of envelope gene sequences was performed in a group of pregnant women infected with HIV-1 of clade B (n=10) or non-B (n=9). Polymerase chain reaction (PCR) amplification of the V1-V3 region was performed on plasma viral RNA, followed by cloning and sequencing. Using geno2pheno and PSSMX4R5, the presence of X4 variants was predicted in nine of 19 subjects (X4 subjects) independent of HIV-1 clade. Six of nine X4 subjects exhibited CD4(+) T cell counts pregnancy, invariably accompanied by progressive increases in the PSSMX4R5 score, the net charge of V3, and the relative representation of X4 sequences. Evolution toward X4 tropism was also echoed in the primary structure of V2, as an accumulation of substitutions associated with CXCR4 tropism was seen in X4 subjects. Results from these experiments provide the first evidence of the ongoing evolution of coreceptor utilization from CCR5 to CXCR4 during pregnancy in a significant fraction of HIV-infected women. These results inform changes in host-pathogen interactions that lead to a directional shaping of viral populations and viral tropism during pregnancy, and provide insights into the biology of HIV transmission from mother to child.

  7. Expanded Dengue.

    Science.gov (United States)

    Kadam, D B; Salvi, Sonali; Chandanwale, Ajay

    2016-07-01

    The World Health Organization (WHO) has coined the term expanded dengue to describe cases which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. This has incorporated several atypical findings of dengue. Dengue virus has not been enlisted as a common etiological agent in several conditions like encephalitis, Guillain Barre syndrome. Moreover it is a great mimic of co-existing epidemics like Malaria, Chikungunya and Zika virus disease, which are also mosquito-borne diseases. The atypical manifestations noted in dengue can be mutisystemic and multifacetal. In clinical practice, the occurrence of atypical presentation should prompt us to investigate for dengue. Knowledge of expanded dengue helps to clinch the diagnosis of dengue early, especially during ongoing epidemics, avoiding further battery of investigations. Dengue has proved to be the epidemic with the ability to recur and has a diverse array of presentation as seen in large series from India, Srilanka, Indonesia and Taiwan. WHO has given the case definition of dengue fever in their comprehensive guidelines. Accordingly, a probable case is defined as acute febrile illness with two or more of any findings viz. headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia and supportive serology. There have been cases of patients admitted with fever, altered mentation with or without neck stiffness and pyramidal tract signs. Some had seizures or status epilepticus as presentation. When they were tested for serology, dengue was positive. After ruling out other causes, dengue remained the only culprit. We have come across varied presentations of dengue fever in clinical practice and the present article throws light on atypical manifestations of dengue. © Journal of the Association of Physicians of India 2011.

  8. Unique glycan signatures regulate adeno-associated virus tropism in the developing brain.

    Science.gov (United States)

    Murlidharan, Giridhar; Corriher, Travis; Ghashghaei, H Troy; Asokan, Aravind

    2015-04-01

    Adeno-associated viruses (AAV) are thought to spread through the central nervous system (CNS) by exploiting cerebrospinal fluid (CSF) flux and hijacking axonal transport pathways. The role of host receptors that mediate these processes is not well understood. In the current study, we utilized AAV serotype 4 (AAV4) as a model to evaluate whether ubiquitously expressed 2,3-linked sialic acid and the developmentally regulated marker 2,8-linked polysialic acid (PSA) regulate viral transport and tropism in the neonatal brain. Modulation of the levels of SA and PSA in cell culture studies using specific neuraminidases revealed possibly opposing roles of the two glycans in AAV4 transduction. Interestingly, upon intracranial injection into lateral ventricles of the neonatal mouse brain, a low-affinity AAV4 mutant (AAV4.18) displayed a striking shift in cellular tropism from 2,3-linked SA(+) ependymal lining to 2,8-linked PSA(+) migrating progenitors in the rostral migratory stream and olfactory bulb. In addition, this gain-of-function phenotype correlated with robust CNS spread of AAV4.18 through paravascular transport pathways. Consistent with these observations, altering glycan dynamics within the brain by coadministering SA- and PSA-specific neuraminidases resulted in striking changes to the cellular tropisms and transduction efficiencies of both parental and mutant vectors. We postulate that glycan signatures associated with host development can be exploited to redirect novel AAV vectors to specific cell types in the brain. Viruses invade the CNS through various mechanisms. In the current study, we utilized AAV as a model to study the dynamics of virus-carbohydrate interactions in the developing brain and their impact on viral tropism. Our findings suggest that carbohydrate content can be exploited to regulate viral transport and tropism in the brain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Cutaneous and mucosal human papillomaviruses differ in net surface charge, potential impact on tropism

    Directory of Open Access Journals (Sweden)

    Wibom Carl

    2008-10-01

    Full Text Available Abstract Papillomaviruses can roughly be divided into two tropism groups, those infecting the skin, including the genus beta PVs, and those infecting the mucosa, predominantly genus alpha PVs. The L1 capsid protein determines the phylogenetic separation between beta types and alpha types and the L1 protein is most probably responsible for the first interaction with the cell surface. Virus entry is a known determinant for tissue tropism and to study if interactions of the viral capsid with the cell surface could affect HPV tropism, the net surface charge of the HPV L1 capsid proteins was analyzed and HPV-16 (alpha and HPV-5 (beta with a mucosal and cutaneous tropism respectively were used to study heparin inhibition of uptake. The negatively charged L1 proteins were all found among HPVs with cutaneous tropism from the beta- and gamma-PV genus, while all alpha HPVs were positively charged at pH 7.4. The linear sequence of the HPV-5 L1 capsid protein had a predicted isoelectric point (pI of 6.59 and a charge of -2.74 at pH 7.4, while HPV-16 had a pI of 7.95 with a charge of +2.98, suggesting no interaction between HPV-5 and the highly negative charged heparin. Furthermore, 3D-modelling indicated that HPV-5 L1 exposed more negatively charged amino acids than HPV-16. Uptake of HPV-5 (beta and HPV-16 (alpha was studied in vitro by using a pseudovirus (PsV assay. Uptake of HPV-5 PsV was not inhibited by heparin in C33A cells and only minor inhibition was detected in HaCaT cells. HPV-16 PsV uptake was significantly more inhibited by heparin in both cells and completely blocked in C33A cells.

  10. Curr Opin HIV AIDS

    OpenAIRE

    Zewdie, D.; Cahn, P.; McClure, C; Bataringaya, J.

    2008-01-01

    PURPOSE OF REVIEW: There is growing recognition that greater investment in research is needed to expand our knowledge and understanding of how to scale up HIV programmes effectively and equitably in the context of weak health systems. Current debates acknowledge that there remains a gap in evidence on how HIV resources can best be managed to contribute to building health system capacity; how to integrate HIV interventions into primary healthcare systems; and how HIV scale-up is affecting othe...

  11. Humanized mice for HIV and AIDS research.

    Science.gov (United States)

    Victor Garcia, J

    2016-08-01

    HIV has a very limited species tropism that prevents the use of most conventional small animal models for AIDS research. The in vivo analysis of HIV/AIDS has benefited extensively from novel chimeric animal models that accurately recapitulate key aspects of the human condition. Specifically, immunodeficient mice that are systemically repopulated with human hematolymphoid cells offer a viable alternative for the study of a multitude of highly relevant aspects of HIV replication, pathogenesis, therapy, transmission, prevention, and eradication. This article summarizes some of the multiple contributions that humanized mouse models of HIV infection have made to the field of AIDS research. These models have proven to be highly informative and hold great potential for accelerating multiple aspects of HIV research in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

    Science.gov (United States)

    Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

    2005-02-01

    Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

  13. In vitro selection of viral vectors with modified tropism: the adeno-associated virus display.

    Science.gov (United States)

    Perabo, Luca; Büning, Hildegard; Kofler, David M; Ried, Martin U; Girod, Anne; Wendtner, Clemens M; Enssle, Jörg; Hallek, Michael

    2003-07-01

    Improving the efficiency and specificity of gene vectors is critical for the success of gene therapy. In an effort to generate viral mutants with controlled tropism we produced a library of adeno-associated virus (AAV) clones with randomly modified capsids and used it for the selection of receptor-targeting mutants. After several rounds of selection on different cell lines that were resistant to infection by wild-type (wt) AAV, infectious mutants were harvested at high titers. These mutants transduced target cells with an up to 100-fold increased efficiency, in a receptor-specific manner and without interacting with the primary receptor for wt AAV. The results demonstrate for the first time that a combinatorial approach based on a eukaryotic virus library allows one to generate efficient, receptor-specific targeting vectors with desired tropism.

  14. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression.

    Directory of Open Access Journals (Sweden)

    James J Zhu

    Full Text Available Foot-and-mouth disease virus (FMDV targets specific tissues for primary infection, secondary high-titer replication (e.g. foot and mouth where it causes typical vesicular lesions and long-term persistence at some primary replication sites. Although integrin αVβ6 receptor has been identified as primary FMDV receptors in animals, their tissue distribution alone fails to explain these highly selective tropism-driven events. Thus, other molecular mechanisms must play roles in determining this tissue specificity. We hypothesized that differences in certain biological activities due to differential gene expression determine FMDV tropism and applied whole genome gene expression profiling to identify genes differentially expressed between FMDV-targeted and non-targeted tissues in terms of supporting primary infection, secondary replication including vesicular lesions, and persistence. Using statistical and bioinformatic tools to analyze the differential gene expression, we identified mechanisms that could explain FMDV tissue tropism based on its association with differential expression of integrin αVβ6 heterodimeric receptor (FMDV receptor, fibronectin (ligand of the receptor, IL-1 cytokines, death receptors and the ligands, and multiple genes in the biological pathways involved in extracellular matrix turnover and interferon signaling found in this study. Our results together with reported findings indicate that differences in (1 FMDV receptor availability and accessibility, (2 type I interferon-inducible immune response, and (3 ability to clear virus infected cells via death receptor signaling play roles in determining FMDV tissue tropism and the additional increase of high extracellular matrix turnover induced by FMDV infection, likely via triggering the signaling of highly expressed IL-1 cytokines, play a key role in the pathogenesis of vesicular lesions.

  15. Pseudotyped Adeno-associated Viral Vector Tropism and Transduction Efficiencies in Murine Wound Healing

    OpenAIRE

    Keswani, Sundeep G.; Balaji, Swathi; Le, Louis; Leung, Alice; Lim, Foong-Yen; Habli, Mounira; Jones, Helen N.; Wilson, James M.; Crombleholme, Timothy M.

    2012-01-01

    Cell specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy for tissue repair and regeneration. Adeno-associated virus serotype 2 (AAV2/2) mediated gene transfer to the skin results in stable transgene expression in the muscle fascicles of the panniculus carnosus in mice, with minimal gene transfer to the dermal or epidermal elements. We hypothesized that pseudotyped AAV vectors may have a unique and characteristic tropism and transduction efficiency pro...

  16. Differential Cellular Tropism of Lentivirus and Adeno-Associated Virus in the Brain of Cynomolgus Monkey.

    Science.gov (United States)

    An, Heeyoung; Cho, Doo-Wan; Lee, Seung Eun; Yang, Young-Su; Han, Su-Cheol; Lee, C Justin

    2016-02-01

    Many researchers are using viruses to deliver genes of interest into the brains of laboratory animals. However, certain target brain cells are not easily infected by viruses. Moreover, the differential tropism of different viruses in monkey brain is not well established. We investigated the cellular tropism of lentivirus and adeno-associated virus (AAV) toward neuron and glia in the brain of cynomolgus monkeys (Macaca fascularis). Lentivirus and AAV were injected into putamen of the monkey brain. One month after injection, monkeys were sacrificed, and then the presence of viral infection by expression of reporter fluorescence proteins was examined. Tissues were sectioned and stained with NeuN and GFAP antibodies for identifying neuronal cells or astrocytes, respectively, and viral reporter GFP-expressing cells were counted. We found that while lentivirus infected mostly astrocytes, AAV infected neurons at a higher rate than astrocytes. Moreover, astrocytes showed reactiveness when cells were infected by virus, likely due to virus-mediated neuroinflammation. The Sholl analysis was done to compare the hypertrophy of infected and uninfected astrocytes by virus. The lentivirus infected astrocytes showed negligible hypertrophy whereas AAV infected astrocytes showed significant changes in morphology, compared to uninfected astrocytes. In the brain of cynomolgus monkey, lentivirus shows tropism for astrocytes over neurons without much reactivity in astrocytes, whereas AAV shows tropism for neurons over glial cells with a significant reactivity in astrocytes. We conclude that AAV is best-suited for gene delivery to neurons, whereas lentivirus is the best choice for gene delivery to astrocytes in the brain of cynomolgus monkeys.

  17. A Unified Model of Shoot Tropism in Plants: Photo-, Gravi- and Propio-ception

    OpenAIRE

    Renaud Bastien; Stéphane Douady; Bruno Moulia

    2015-01-01

    Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation. In natural conditions, these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ. Recently, a parsimonious model was developed that accurately predicted the complete gravitropic and proprioceptive control over the movement of different organs in different species in response to gravitational stimuli. Here we show that the framework of this...

  18. An expanded analysis of pharmacogenetics determinants of efavirenz response that includes 3'-UTR single nucleotide polymorphisms among Black South African HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Marelize eSwart

    2016-01-01

    Full Text Available Introduction: Efavirenz (EFV is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in EFV plasma concentrations has been reported. Poor treatment outcomes such as the development of adverse drug reactions or treatment failure have been linked to EFV concentrations outside the therapeutic range (1 - 4 µg/mL. The drug metabolising enzyme (DME, CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP2A6, CYP3A4, CYP3A5, UGT2B7 and CYP1A2. Genes coding for DMEs have been shown to be regulated by microRNAs through targeting the 3'-untranslated region. Genetic variation in the 3'-UTR, in addition to genetic variation in the coding regions, could potentially be used to explain a larger proportion of the inter-individual variability observed in drug response. Methods: SNPs in CYP1A2, CYP2B6, UGT2B7 and NR1I2 (PXR were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing specifically the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV.Results: In addition to CYP2B6 c.516G>T and c.983T>C SNPs, the CYP2B6 c.1355A>G SNP was identified as pharmacogenetics determinant of EFV concentration among CYP2B6 intermediate and extensive metabolisers (carriers of either c.516G/G+c.983T/T or c.516G/G+c.983T/C or c.516G/T+c.983T/T genotypes. NR1I2 c.522C>T and NR1I3 c.239-1089T>C SNPs were predictors of EFV concentration among CYP2B6 poor metabolisers (carriers of either c.516T/T or c.983C/C or both c.516G/T and c.983T/C genotypes.Conclusion: Genotyping results provide support for comprehensive studies of genetic variation in the 3'-UTR of genes coding for DMEs and their

  19. Peste des Petits Ruminants Virus Tissue Tropism and Pathogenesis in Sheep and Goats following Experimental Infection

    Science.gov (United States)

    Truong, Thang; Boshra, Hani; Embury-Hyatt, Carissa; Nfon, Charles; Gerdts, Volker; Tikoo, Suresh; Babiuk, Lorne A.; Kara, Pravesh; Chetty, Thireshni; Mather, Arshad; Wallace, David B.; Babiuk, Shawn

    2014-01-01

    Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions. PMID:24498032

  20. Oncolytic virotherapy synergism with signaling inhibitors: Rapamycin increases myxoma virus tropism for human tumor cells.

    Science.gov (United States)

    Stanford, Marianne M; Barrett, John W; Nazarian, Steven H; Werden, Steven; McFadden, Grant

    2007-02-01

    Myxoma virus is a rabbit-specific poxvirus pathogen that also exhibits a unique tropism for human tumor cells and is dramatically oncolytic for human cancer xenografts. Most tumor cell lines tested are permissive for myxoma infection in a fashion intimately tied to the activation state of Akt kinase. A host range factor of myxoma virus, M-T5, directly interacts with Akt and mediates myxoma virus tumor cell tropism. mTOR is a regulator of cell growth and metabolism downstream of Akt and is specifically inhibited by rapamycin. We report that treatment of nonpermissive human tumor cell lines, which normally restrict myxoma virus replication, with rapamycin dramatically increased virus tropism and spread in vitro. This increased myxoma replication is concomitant with global effects on mTOR signaling, specifically, an increase in Akt kinase. In contrast to the effects on human cancer cells, rapamycin does not increase myxoma virus replication in rabbit cell lines or permissive human tumor cell lines with constitutively active Akt. This indicates that rapamycin increases the oncolytic capacity of myxoma virus for human cancer cells by reconfiguring the internal cell signaling environment to one that is optimal for productive virus replication and suggests the possibility of a potentially therapeutic synergism between kinase signaling inhibitors and oncolytic poxviruses for cancer treatment.

  1. HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation.

    Science.gov (United States)

    Tsang, Jhen; Chain, Benjamin M; Miller, Robert F; Webb, Benjamin L J; Barclay, Wendy; Towers, Greg J; Katz, David R; Noursadeghi, Mahdad

    2009-11-13

    The cellular innate immune response to HIV-1 is poorly characterized. In view of HIV-1 tropism for macrophages, which can be activated via pattern recognition receptors to trigger antimicrobial defences, we investigated innate immune responses to HIV-1 by monocyte-derived macrophages. In a model of productive HIV-1 infection, cellular innate immune responses to HIV-1 were investigated, at the level of transcription factor activation, specific gene expression and genome-wide transcriptional profiling. In addition, the viral determinants of macrophage responses and the physiological effect of innate immune cellular activation on HIV-1 replication were assessed. Productive HIV-1 infection did not activate nuclear factor-kappaB and interferon regulatory factor 3 transcription factors or interferon gene expression (IFN) and caused remarkably small changes to the host-cell transcriptome, with no evidence of inflammatory or IFN signatures. Evasion of IFN induction was not dependent on HIV-1 envelope-mediated cellular entry, inhibition by accessory proteins or reverse transcription of ssRNA that may reduce innate immune cellular activation by viral RNA. Furthermore, IFNbeta priming did not sensitize responses to HIV-1. Importantly, exogenous IFNbeta or stimulation with the RNA analogue poly I:C to simulate innate immune activation invoked HIV-1 restriction. We conclude that macrophages lack functional pattern recognition receptors for this virus and that HIV-1 tropism for macrophages helps to establish a foothold in the host without triggering innate immune cellular activation, which would otherwise block viral infection effectively.

  2. What is an Investigational HIV Drug?

    Science.gov (United States)

    ... Find HIV Treatment Services HIV and Mental Health HIV and Nutrition and Food Safety Print This Fact Sheet Entire Series Related Content ClinicalTrials.gov Expanded Access: Information for Patients HIV/AIDS Overview Need Help? Call 1-800-448- ...

  3. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  4. PrPSc formation and clearance as determinants of prion tropism.

    Science.gov (United States)

    Shikiya, Ronald A; Langenfeld, Katie A; Eckland, Thomas E; Trinh, Jonathan; Holec, Sara A M; Mathiason, Candace K; Kincaid, Anthony E; Bartz, Jason C

    2017-03-01

    Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPSc as the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPSc formation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPSc is more susceptible to degradation when compared to PrPSc from other lymphotrophic strains. We hypothesize that the relative rates of PrPSc formation and clearance can influence prion tropism.

  5. Cell tropism predicts long-term nucleotide substitution rates of mammalian RNA viruses.

    Directory of Open Access Journals (Sweden)

    Allison L Hicks

    2014-01-01

    Full Text Available The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001 as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively. These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.

  6. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern

    2005-01-01

    . The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....... and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right...

  7. Robust supervised and unsupervised statistical learning for HIV type 1 coreceptor usage analysis.

    Science.gov (United States)

    Prosperi, Mattia C F; Fanti, Iuri; Ulivi, Giovanni; Micarelli, Alessandro; De Luca, Andrea; Zazzi, Maurizio

    2009-03-01

    Human immunodeficiency virus type 1 (HIV-1) isolates differ in their use of coreceptors to enter target cells. This has important implications for both viral pathogenicity and susceptibility to entry inhibitors, recently approved or under development. Predicting HIV-1 coreceptor usage on the basis of sequence information is a challenging task, due to the high variability of the envelope. The associations of the whole HIV-1 envelope genetic features (subtype, mutations, insertions-deletions, physicochemical properties) and clinical markers (viral RNA load, CD8(+), CD4(+) T cell counts) with viral tropism were investigated, using a set of 2896 (659 after filter, 593 patients) sequence-tropism pairs available at the Los Alamos HIV database. Bootstrapped hierarchical clustering was used to assess mutational covariation. Univariate and multivariate analysis was performed to assess the relative importance of different features. Different machine learning (logistic regression, support vector machines, decision trees, rule bases, instance based reasoning) and feature selection (filter and embedded) methods, along with loss functions (accuracy, AUC of ROC curves, sensitivity, specificity, f-measure), were applied and compared for the classification of X4 variants. Extra-sample error estimation was assessed via multiple cross-validation and adjustments for multiple testing. A high-performing, compact, and interpretable logistic regression model was derived to infer HIV-1 coreceptor tropism for a given patient [accuracy = 92.76 (SD 3.07); AUC = 0.93 (SD 0.04)].

  8. Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species.

    Directory of Open Access Journals (Sweden)

    Smanla Tundup

    2017-03-01

    Full Text Available The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown. Here, we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species. We engineered H5N1 viruses with restricted cell tropism through the exploitation of cell type-specific microRNA expression by incorporating microRNA target sites into the viral genome. Restriction of H5N1 replication in endothelial cells via miR-126 ameliorated disease symptoms, prevented systemic viral spread and limited mortality, despite showing similar levels of peak viral replication in the lungs as compared to control virus-infected mice. Similarly, restriction of H5N1 replication in endothelial cells resulted in ameliorated disease symptoms and decreased viral spread in ferrets. Our studies demonstrate that H5N1 infection of endothelial cells results in excessive production of cytokines and reduces endothelial barrier integrity in the lungs, which culminates in vascular leakage and viral pneumonia. Importantly, our studies suggest a need for a combinational therapy that targets viral components, suppresses host immune responses, and improves endothelial barrier integrity for the treatment of highly pathogenic H5N1 virus infections.

  9. Predicting Zoonotic Risk of Influenza A Viruses from Host Tropism Protein Signature Using Random Forest

    Directory of Open Access Journals (Sweden)

    Christine L. P. Eng

    2017-05-01

    Full Text Available Influenza A viruses remain a significant health problem, especially when a novel subtype emerges from the avian population to cause severe outbreaks in humans. Zoonotic viruses arise from the animal population as a result of mutations and reassortments, giving rise to novel strains with the capability to evade the host species barrier and cause human infections. Despite progress in understanding interspecies transmission of influenza viruses, we are no closer to predicting zoonotic strains that can lead to an outbreak. We have previously discovered distinct host tropism protein signatures of avian, human and zoonotic influenza strains obtained from host tropism predictions on individual protein sequences. Here, we apply machine learning approaches on the signatures to build a computational model capable of predicting zoonotic strains. The zoonotic strain prediction model can classify avian, human or zoonotic strains with high accuracy, as well as providing an estimated zoonotic risk. This would therefore allow us to quickly determine if an influenza virus strain has the potential to be zoonotic using only protein sequences. The swift identification of potential zoonotic strains in the animal population using the zoonotic strain prediction model could provide us with an early indication of an imminent influenza outbreak.

  10. A Unified Model of Shoot Tropism in Plants: Photo-, Gravi- and Propio-ception

    Science.gov (United States)

    Bastien, Renaud; Douady, Stéphane; Moulia, Bruno

    2015-01-01

    Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation. In natural conditions, these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ. Recently, a parsimonious model was developed that accurately predicted the complete gravitropic and proprioceptive control over the movement of different organs in different species in response to gravitational stimuli. Here we show that the framework of this unifying graviproprioceptive model can be readily extended to include phototropism. The interaction between gravitropism and phototropism results in an alignment of the apical part of the organ toward a photogravitropic set-point angle. This angle is determined by a combination of the two directional stimuli, gravity and light, weighted by the ratio between the gravi- and photo-sensitivities of the plant organ. In the model, two dimensionless numbers, the graviproprioceptive number B and the photograviceptive number M, control the dynamics and the shapes of the movement. The extended model agrees well with two sets of detailed quantitative data on photogravitropic equilibrium in oat coleoptiles. It is demonstrated that the influence of light intensity I can be included in the model in a power-law-dependent relationship M(I). The numbers B and M and the related photograviceptive number D are all quantitative genetic traits that can be measured in a straightforward manner, opening the way to the phenotyping of molecular and mechanical aspects of shoot tropism. PMID:25692607

  11. Comparative development and tissue tropism of Nosema apis and Nosema ceranae.

    Science.gov (United States)

    Huang, Wei-Fone; Solter, Leellen F

    2013-05-01

    The two etiological agents of nosema disease in honey bees, Nosema apis and Nosema ceranae (Microsporidia: Nosematidae), reproduce in the midgut tissues of the host. N. apis is tissue specific but the development and tissue tropism of N. ceranae is not well understood. Our investigations compared development of the two phylogenetically related pathogens in all major host tissues. Using microscopy, PCR and qPCR quantification to evaluate tissue tropism of infected bees in communal cages and of individually restrained infected bees, we found no detectable spores in cephalic or other body tissues except midgut tissues. Nosema DNA was detected in Malpighian tubules but the tubules could not be separated from the alimentary tract without release of spores from the midgut. Nosema DNA was not detected in hemolymph sampled from the head capsule or the abdomen of infected bees. We confirmed that N. ceranae only develops in midgut tissues. Spores of both species released from host midgut cells accumulated in the hindgut lumen, and we noted differences in numbers and ratios of spore types and in growth curves between the two pathogens. N. apis reached a consistent level of spore production after 12 days post inoculation (dpi); N. ceranae spore production increased linearly from 12 to 20 dpi and the number of mature N. ceranae spores was consistently higher. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Neutralization-resistant variants of infectious hematopoietic necrosis virus have altered virulence and tissue tropism

    Science.gov (United States)

    Kim, C.H.; Winton, J.R.; Leong, J.C.

    1994-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that causes an acute disease in salmon and trout. In this study, a correlation between changes in tissue tropism and specific changes in the virus genome appeared to be made by examining four IHNV neutralization-resistant variants (RB-1, RB-2, RB-3, and RB-4) that had been selected with the glycoprotein (G)-specific monoclonal antibody RB/B5. These variants were compared with the parental strain (RB-76) for their virulence and pathogenicity in rainbow trout after waterborne challenge. Variants RB-2, RB-3, and RB-4 were only slightly attenuated and showed distributions of viral antigen in the livers and hematopoietic tissues of infected fish similar to those of the parental strain. Variant RB-1, however, was highly attenuated and the tissue distribution of viral antigen in RB-1-infected fish was markedly different, with more viral antigen in brain tissue. The sequences of the G genes of all four variants and RB-76 were determined. No significant changes were found for the slightly attenuated variants, but RB-1 G had two changes at amino acids 78 and 218 that dramatically altered its predicted secondary structure. These changes are thought to be responsible for the altered tissue tropism of the virus. Thus, IHNV G, like that of rabies virus and vesicular stomatitis virus, plays an integral part in the pathogenesis of viral infection.

  13. Canine Cutaneous Leishmaniasis: Dissemination and Tissue Tropism of Genetically Distinct Leishmania (Viannia braziliensis Populations

    Directory of Open Access Journals (Sweden)

    Guilherme Marx de Oliveira

    2013-01-01

    Full Text Available Little is known regarding the internal dissemination of initial cutaneous lesions and tissue tropism of Leishmania (Viannia braziliensis populations in naturally infected dogs. The aim of this study was to investigate genetic polymorphisms of L. (V. braziliensis populations in different anatomic sites of naturally infected dogs by using polymerase chain reaction (PCR and low-stringency single specific primer-PCR (LSSP-PCR techniques. The amplified products were analyzed by LSSP-PCR to investigate the genetic variability of the parasite populations present in different anatomical sites. Twenty-three out of the 52 samples gave PCR-positive results. The existence of L. (V. braziliensis strains that remained restricted to cutaneous lesions and others showing characteristics of dissemination to internal organs and healthy skin was observed. LSSP-PCR and numerical analyses revealed that parasite populations that do not disseminate were genetically similar and belonged to a separate phenetic cluster. In contrast, populations that showed spreading to internal organs displayed a more polymorphic genetic profile. Despite the heterogeneity, L. (V. braziliensis populations with identical genetic profiles were observed in popliteal and cervical lymph nodes of the same animal. Our results indicate that infection in dogs can be manifested by dissemination and tissue tropism of genetically distinct populations of L. (V. braziliensis.

  14. A unified model of shoot tropism in plants: photo-, gravi- and Propio-ception.

    Directory of Open Access Journals (Sweden)

    Renaud Bastien

    2015-02-01

    Full Text Available Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation. In natural conditions, these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ. Recently, a parsimonious model was developed that accurately predicted the complete gravitropic and proprioceptive control over the movement of different organs in different species in response to gravitational stimuli. Here we show that the framework of this unifying graviproprioceptive model can be readily extended to include phototropism. The interaction between gravitropism and phototropism results in an alignment of the apical part of the organ toward a photogravitropic set-point angle. This angle is determined by a combination of the two directional stimuli, gravity and light, weighted by the ratio between the gravi- and photo-sensitivities of the plant organ. In the model, two dimensionless numbers, the graviproprioceptive number B and the photograviceptive number M, control the dynamics and the shapes of the movement. The extended model agrees well with two sets of detailed quantitative data on photogravitropic equilibrium in oat coleoptiles. It is demonstrated that the influence of light intensity I can be included in the model in a power-law-dependent relationship M(I. The numbers B and M and the related photograviceptive number D are all quantitative genetic traits that can be measured in a straightforward manner, opening the way to the phenotyping of molecular and mechanical aspects of shoot tropism.

  15. HIV status and participation in HIV surveillance in the era of antiretroviral treatment: a study of linked population‐based and clinical data in rural South Africa

    National Research Council Canada - National Science Library

    Bärnighausen, T; Tanser, F; Malaza, A; Herbst, K; Newell, M. ‐L

    2012-01-01

    Objective  To examine whether HIV status affects participation in a population‐based longitudinal HIV surveillance in the context of an expanding HIV treatment and care programme in rural South Africa. Method...

  16. The expanding universe of prion diseases.

    Directory of Open Access Journals (Sweden)

    Joel C Watts

    2006-03-01

    Full Text Available Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C. Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases--including human diseases variant Creutzfeldt-Jakob disease (vCJD and sporadic fatal insomnia (sFI, bovine amyloidotic spongiform encephalopathy (BASE, and Nor98 of sheep--have been identified in the last ten years, and chronic wasting disease (CWD of North American deer (Odocoileus Specis and Rocky Mountain elk (Cervus elaphus nelsoni is undergoing a dramatic spread across North America. While amplification (BSE and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

  17. The expanding universe of prion diseases.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C. Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases-including human diseases variant Creutzfeldt-Jakob disease (vCJD and sporadic fatal insomnia (sFI, bovine amyloidotic spongiform encephalopathy (BASE, and Nor98 of sheep-have been identified in the last ten years, and chronic wasting disease (CWD of North American deer (Odocoileus Specis and Rocky Mountain elk (Cervus elaphus nelsoni is undergoing a dramatic spread across North America. While amplification (BSE and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

  18. Association of facet tropism and progressive facet arthrosis after lumbar total disc replacement using ProDisc-L.

    Science.gov (United States)

    Shin, Myung-Hoon; Ryu, Kyeong-Sik; Hur, Jung-Woo; Kim, Jin-Sung; Park, Chun-Kun

    2013-08-01

    The purpose of this retrospective study was to examine the association of facet tropism and progressive facet arthrosis (PFA) after lumbar total disc replacement (TDR) surgery using ProDisc-L. A total of 51 segments of 42 patients who had undergone lumbar TDR using ProDisc-L between October 2003 and July 2007 and completed minimum 36-month follow-up period were retrospectively reviewed. The changes of facet arthrosis were categorized as non-PFA and PFA group. Comparison between non-PFA and PFA group was made according to age, sex, mean follow-up duration, grade of preoperative facet arthrosis, coronal and sagittal prosthetic position and degree of facet tropism. Multiple logistic regression analysis was also performed to analyze the effect of facet tropism on the progression of facet arthrosis. The mean age at the surgery was 44.43 ± 11.09 years and there were 16 males and 26 females. The mean follow-up period was 53.18 ± 15.79 months. Non-PFA group was composed of 19 levels and PFA group was composed of 32 levels. Age at surgery, sex proportion, mean follow-up period, level of implant, grade of preoperative facet arthrosis and coronal and sagittal prosthetic position were not significantly different between two groups (p = 0.264, 0.433, 0.527, 0.232, 0.926, 0.849 and 0.369, respectively). However, PFA group showed significantly higher degree of facet tropism (7.37 ± 6.46°) than that of non-PFA group (3.51 ± 3.53°) and p value was 0.008. After adjustment for age, sex and coronal and sagittal prosthetic position, multiple logistic regression analysis revealed that facet tropism of more than 5° was the only significant independent predictor of progression of facet arthrosis (odds ratio 5.39, 95 % confidence interval 1.251-19.343, p = 0.023). The data demonstrate that significant higher degree of facet tropism was seen in PFA group compared with non-PFA group and facet tropism of more than 5° had a significant association with PFA after TDR using ProDisc-L.

  19. Short Communication: Evolution of HIV-1 Coreceptor Usage and Coreceptor Switching During Pregnancy

    Science.gov (United States)

    Ransy, Doris G.; Motorina, Alena; Merindol, Natacha; Akouamba, Bertine S.; Samson, Johanne; Lie, Yolanda; Napolitano, Laura A.; Lapointe, Normand; Boucher, Marc

    2014-01-01

    Abstract Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. To document the evolution of coreceptor tropism during pregnancy, a longitudinal study of envelope gene sequences was performed in a group of pregnant women infected with HIV-1 of clade B (n=10) or non-B (n=9). Polymerase chain reaction (PCR) amplification of the V1-V3 region was performed on plasma viral RNA, followed by cloning and sequencing. Using geno2pheno and PSSMX4R5, the presence of X4 variants was predicted in nine of 19 subjects (X4 subjects) independent of HIV-1 clade. Six of nine X4 subjects exhibited CD4+ T cell counts false-positive rate was observed during the course of pregnancy, invariably accompanied by progressive increases in the PSSMX4R5 score, the net charge of V3, and the relative representation of X4 sequences. Evolution toward X4 tropism was also echoed in the primary structure of V2, as an accumulation of substitutions associated with CXCR4 tropism was seen in X4 subjects. Results from these experiments provide the first evidence of the ongoing evolution of coreceptor utilization from CCR5 to CXCR4 during pregnancy in a significant fraction of HIV-infected women. These results inform changes in host–pathogen interactions that lead to a directional shaping of viral populations and viral tropism during pregnancy, and provide insights into the biology of HIV transmission from mother to child. PMID:24090041

  20. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  1. Phylogenetically distinct equine influenza viruses show different tropism for the swine respiratory tract.

    Science.gov (United States)

    Patrono, Livia V; Bonfante, Francesco; Zanardello, Claudia; Terregino, Calogero; Capua, Ilaria; Murcia, Pablo R

    2015-05-01

    Influenza A viruses circulate in a wide range of animals. H3N8 equine influenza virus (EIV) is an avian-origin virus that has established in dogs as canine influenza virus (CIV) and has also been isolated from camels and pigs. Previous work suggests that mutations acquired during EIV evolution might have played a role in CIV emergence. Given the potential role of pigs as a source of human infections, we determined the ability of H3N8 EIVs to replicate in pig cell lines and in respiratory explants. We show that phylogenetically distinct EIVs display different infection phenotypes along the pig respiratory tract, but not in cell lines. Our results suggest that EIV displays a dynamic host range along its evolutionary history, supporting the view that evolutionary processes play important roles in host range and tropism and also underscoring the utility of using explant cultures to study influenza pathogenesis. © 2015 The Authors.

  2. Salivary gland morphology, tissue tropism and the progression of tospovirus infection in Frankliniella occidentalis.

    Science.gov (United States)

    Montero-Astúa, Mauricio; Ullman, Diane E; Whitfield, Anna E

    2016-06-01

    Tomato spotted wilt virus (TSWV) is transmitted by thrips in a propagative manner; however, progression of virus infection in the insect is not fully understood. The goal of this work was to study the morphology and infection of thrips salivary glands. The primary salivary glands (PSG) are complex, with three distinct regions that may have unique functions. Analysis of TSWV progression in thrips revealed the presence of viral proteins in the foregut, midgut, ligaments, tubular salivary glands (TSG), and efferent duct and filament structures connecting the TSG and PSG of first and second instar larvae. The primary site of virus infection shifted from the midgut and TSG in the larvae to the PSG in adults, suggesting that tissue tropism changes with insect development. TSG infection was detected in advance of PSG infection. These findings support the hypothesis that the TSG are involved in trafficking of TSWV to the PSG. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages.

    Directory of Open Access Journals (Sweden)

    Christiane E Wobus

    2004-12-01

    Full Text Available Noroviruses are understudied because these important enteric pathogens have not been cultured to date. We found that the norovirus murine norovirus 1 (MNV-1 infects macrophage-like cells in vivo and replicates in cultured primary dendritic cells and macrophages. MNV-1 growth was inhibited by the interferon-alphabeta receptor and STAT-1, and was associated with extensive rearrangements of intracellular membranes. An amino acid substitution in the capsid protein of serially passaged MNV-1 was associated with virulence attenuation in vivo. This is the first report of replication of a norovirus in cell culture. The capacity of MNV-1 to replicate in a STAT-1-regulated fashion and the unexpected tropism of a norovirus for cells of the hematopoietic lineage provide important insights into norovirus biology.

  4. Neural Processing of Auditory Signals and Modular Neural Control for Sound Tropism of Walking Machines

    Directory of Open Access Journals (Sweden)

    Hubert Roth

    2008-11-01

    Full Text Available The specialized hairs and slit sensillae of spiders (Cupiennius salei can sense the airflow and auditory signals in a low-frequency range. They provide the sensor information for reactive behavior, like e.g. capturing a prey. In analogy, in this paper a setup is described where two microphones and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right. The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it.

  5. Vertebral rotatory subluxation in degenerative scoliosis: facet joint tropism is related.

    Science.gov (United States)

    Bao, Hongda; Zhu, Feng; Liu, Zhen; Bentley, Mark; Mao, Saihu; Zhu, Zezhang; Ding, Yitao; Qiu, Yong

    2014-12-15

    A cross-sectional study. To identify facet tropism as one of the possible risk factors leading to vertebral rotatory subluxation (VRS). VRS has been considered as one of the prognostic factors for degenerative scoliosis. Although several risk factors of VRS, including age and Cobb angle, have been investigated, few studies exist that have evaluated the correlation between VRS and anatomical structures of the vertebral column. This retrospective study recruited 23 patients diagnosed with degenerative lumbar scoliosis with VRS and 20 patients with degenerative scoliosis without VRS. The lateral translation on coronal radiographs was measured and 5 mm was used as the cutoff value to define rotatory subluxation. Computed tomographic scans for facet joints were made for all lumbar levels. The difference between right and left facet angles was recorded as ΔFA. Facet tropism was defined as a difference between the bilateral facet angles of more than 10°. In this study, VRS was most commonly found at the L3-L4 level (49%) and, with decreasing frequency at L2-L3 (24%), L4-L5 (20%), and L1-L2 (7%). On the convex side of the main curve, face joints at levels with VRS were more coronally oriented compared with those at levels without VRS (41.64° ± 11.65° vs. 36.30° ± 10.99°, P = 0.034). ΔFA was also significantly different between levels with and without VRS (P = 0.005). A strong correlation was found between ΔFA and lateral translation, with a coefficient of 0.33 (P scoliosis should be considered to be related to VRS.

  6. Genotypic tropism testing by massively parallel sequencing: qualitative and quantitative analysis

    Directory of Open Access Journals (Sweden)

    Thiele Bernhard

    2011-05-01

    Full Text Available Abstract Background Inferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4 variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing. Massively parallel sequencing (MPS detects single clones thereby being much more sensitive. Using this technology we wanted to improve genotypic prediction of coreceptor usage. Methods Plasma samples from 55 antiretroviral-treated patients tested for coreceptor usage with the Monogram Trofile Assay were sequenced with standard population-based approaches. Fourteen of these samples were selected for further analysis with MPS. Tropism was predicted from each sequence with geno2pheno[coreceptor]. Results Prediction based on bulk-sequencing yielded 59.1% sensitivity and 90.9% specificity compared to the trofile assay. With MPS, 7600 reads were generated on average per isolate. Minorities of sequences with high confidence in CXCR4-usage were found in all samples, irrespective of phenotype. When using the default false-positive-rate of geno2pheno[coreceptor] (10%, and defining a minority cutoff of 5%, the results were concordant in all but one isolate. Conclusions The combination of MPS and coreceptor usage prediction results in a fast and accurate alternative to phenotypic assays. The detection of X4-viruses in all isolates suggests that coreceptor usage as well as fitness of minorities is important for therapy outcome. The high sensitivity of this technology in combination with a quantitative description of the viral population may allow implementing meaningful cutoffs for predicting response to CCR5-antagonists in the presence of X4-minorities.

  7. Drosophila melanogaster as a Model Organism for Bluetongue Virus Replication and Tropism

    Science.gov (United States)

    Shaw, Andrew E.; Veronesi, Eva; Maurin, Guillemette; Ftaich, Najate; Guiguen, Francois; Rixon, Frazer; Ratinier, Maxime; Mertens, Peter; Carpenter, Simon; Palmarini, Massimo; Terzian, Christophe

    2012-01-01

    Bluetongue virus (BTV) is the etiological agent of bluetongue (BT), a hemorrhagic disease of ruminants that can cause high levels of morbidity and mortality. BTV is an arbovirus transmitted between its ruminant hosts by Culicoides biting midges (Diptera: Ceratopogonidae). Recently, Europe has experienced some of the largest BT outbreaks ever recorded, including areas with no known history of the disease, leading to unprecedented economic and animal welfare issues. The current lack of genomic resources and genetic tools for Culicoides restricts any detailed study of the mechanisms involved in the virus-insect interactions. In contrast, the genome of the fruit fly (Drosophila melanogaster) has been successfully sequenced, and it is used extensively as a model of molecular pathways due to the existence of powerful genetic technology. In this study, D. melanogaster is investigated as a model for the replication and tropism of BTV. Using reverse genetics, a modified BTV-1 that expresses the fluorescent mCherry protein fused to the viral nonstructural protein NS3 (BTV-1/NS3mCherry) was generated. We demonstrate that BTV-1/NS3mCherry is not only replication competent as it retains many characteristics of the wild-type virus but also replicates efficiently in D. melanogaster after removal of the bacterial endosymbiont Wolbachia pipientis by antibiotic treatment. Furthermore, confocal microscopy shows that the tissue tropism of BTV-1/NS3mCherry in D. melanogaster resembles that described previously for BTV in Culicoides. Overall, the data presented in this study demonstrate the feasibility of using D. melanogaster as a genetic model to investigate BTV-insect interactions that cannot be otherwise addressed in vector species. PMID:22674991

  8. Dynamic distribution and tissue tropism of classical swine fever virus in experimentally infected pigs

    Science.gov (United States)

    2011-01-01

    Background Classical swine fever (CSF), caused by the Classical swine fever virus (CSFV), is an Office International des Epizooties (OIE) notifiable disease. However, we are far from fully understand the distribution, tissue tropism, pathogenesis, replication and excretion of CSFV in pigs. In this report, we investigated the dynamic distribution and tissue tropism of the virus in internal organs of the experimentally infected pigs using real-time RT-PCR and immunohistochemistry (IHC). Results A relative quantification real-time PCR was established and used to detect the virus load in internal organs of the experimentally infected pigs. The study revealed that the virus was detected in all 21 of the internal organs and blood collected from pigs at day 1 to day 8 post infections, and had an increasing virus load from day 1 to day 8 post infections. However, there was irregular distribution virus load in most internal organs over the first 2 days post infection. Blood, lymphoid tissue, pancreas and ileum usually contain the highest viral loads, while heart, duodenum and brain show relatively low viral loads. Conclusions All the data suggest that CSFV had an increasing virus load from day 1 to day 8 post infections in experimentally infected pigs detected by real-time RT-PCR, which was in consistent with the result of the IHC staining. The data also show that CSFV was likely to reproduce in blood, lymphoid tissue, pancreas and the ileum, while unlikely to replicate in the heart, duodenum and brain. The results provide a foundation for further clarification of the pathogenic mechanism of CSFV in internal organs, and indicate that blood, lymphoid tissue, pancreas and ileum may be preferred sites of acute infection. PMID:21535885

  9. What Expands in an Expanding Universe?

    Directory of Open Access Journals (Sweden)

    JOSÉ A. DE FREITAS PACHECO

    2015-12-01

    Full Text Available ABSTRACT In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  10. What Expands in an Expanding Universe?

    Science.gov (United States)

    Pacheco, José A De Freitas

    2015-01-01

    In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  11. Layouts of Expander Graphs

    OpenAIRE

    Dujmović, Vida; Sidiropoulos, Anastasios; Wood, David R.

    2015-01-01

    Bourgain and Yehudayoff recently constructed $O(1)$-monotone bipartite expanders. By combining this result with a generalisation of the unraveling method of Kannan, we construct 3-monotone bipartite expanders, which is best possible. We then show that the same graphs admit 3-page book embeddings, 2-queue layouts, 4-track layouts, and have simple thickness 2. All these results are best possible.

  12. HIV Transmission

    Science.gov (United States)

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

  13. Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain

    OpenAIRE

    Sandro Alves; Julia Bode; Alexis-Pierre Bemelmans; Christof von Kalle; Nathalie Cartier; Björn Tews

    2016-01-01

    Recombinant adeno-associated viral (AAV) vectors have advanced to the vanguard of gene therapy. Numerous naturally occurring serotypes have been used to target cells in various tissues. There is a strong need for fast and dynamic methods which efficiently unravel viral tropism in whole organs. Ultramicroscopy (UM) is a novel fluorescence microscopy technique that images optically cleared undissected specimens, achieving good resolutions at high penetration depths while being non-destructive. ...

  14. Tissue tropisms in group A Streptococcus: what virulence factors distinguish pharyngitis from impetigo strains?

    Science.gov (United States)

    Bessen, Debra E

    2016-06-01

    Group A streptococci (GAS) are a common cause of pharyngitis and impetigo, and distinct throat strains and skin strains have been long recognized. This review aims to describe recent advances in molecular differences between throat and skin strains, and the pathogenic mechanisms used by virulence factors that may distinguish between these two groups. Recent findings include a new typing scheme for GAS strains based on sequence clusters of genes encoding the entire surface-exposed portion of M protein; correlations between emm-based typing schemes, clinical disease and surface adhesins; covalent bond formation mediated by GAS pili and other adhesins in binding to host ligands; a key role for superantigens in oropharyngeal infection via binding major histocompatibility complex class II antigen; and migration of GAS-specific Th17 cells from the upper respiratory tract to the brain, which may be relevant to autoimmune sequelae. The gap between molecular markers of disease (correlation) and virulence mechanisms (causation) in the establishment of tissue tropisms for GAS infection currently remains wide, but the gap also continues to narrow. Whole genome sequencing combined with mutant construction and improvements in animal models for oropharyngeal infection by GAS may help pave the way for new discoveries.

  15. The genetic basis of plasmid tropism between Chlamydia trachomatis and Chlamydia muridarum.

    Science.gov (United States)

    Wang, Yibing; Cutcliffe, Lesley T; Skilton, Rachel J; Ramsey, Kyle H; Thomson, Nicholas R; Clarke, Ian N

    2014-10-01

    The development of genetic transformation technology for Chlamydia trachomatis using its endogenous plasmid has recently been described. Chlamydia muridarum cannot be transformed by the C. trachomatis plasmid, indicating a barrier between chlamydial species. To determine which regions of the plasmid conferred the species specificity, we used the novel approach of transforming wild-type C. muridarum carrying the endogenous plasmid pNigg and forced recombination with the C. trachomatis vector pGFP::SW2 which carries the complete C. trachomatis plasmid (pSW2). Penicillin and chloramphenicol-resistant transformants expressing the green fluorescent protein were selected. Recovery of plasmids from these transformants showed they were recombinants. The differences between the pSW2 and pNigg allowed identification of the recombination breakpoints and showed that pGFP::SW2 had exchanged a ~ 1 kbp region with pNigg covering CDS 2. The recombinant plasmid (pSW2NiggCDS2) is maintained under antibiotic selection when transformed into plasmid-cured C. muridarum. The ability to select for recombinants in C. muridarum shows that the barrier is not at transformation, but at the level of plasmid replication or maintenance. Our studies show that CDS 2, together with adjoining sequences, is the main determinant of plasmid tropism. © 2014 The Authors. Pathogens and Disease published by John Wiley & Sons on behalf of the Federation of European Microbiological Societies.

  16. The genetic basis of plasmid tropism between Chlamydia trachomatis and Chlamydia muridarum

    Science.gov (United States)

    Wang, Yibing; Cutcliffe, Lesley T; Skilton, Rachel J; Ramsey, Kyle H; Thomson, Nicholas R; Clarke, Ian N

    2014-01-01

    The development of genetic transformation technology for Chlamydia trachomatis using its endogenous plasmid has recently been described. Chlamydia muridarum cannot be transformed by the C. trachomatis plasmid, indicating a barrier between chlamydial species. To determine which regions of the plasmid conferred the species specificity, we used the novel approach of transforming wild-type C. muridarum carrying the endogenous plasmid pNigg and forced recombination with the C. trachomatis vector pGFP::SW2 which carries the complete C. trachomatis plasmid (pSW2). Penicillin and chloramphenicol-resistant transformants expressing the green fluorescent protein were selected. Recovery of plasmids from these transformants showed they were recombinants. The differences between the pSW2 and pNigg allowed identification of the recombination breakpoints and showed that pGFP::SW2 had exchanged a ∼ 1 kbp region with pNigg covering CDS 2. The recombinant plasmid (pSW2NiggCDS2) is maintained under antibiotic selection when transformed into plasmid-cured C. muridarum. The ability to select for recombinants in C. muridarum shows that the barrier is not at transformation, but at the level of plasmid replication or maintenance. Our studies show that CDS 2, together with adjoining sequences, is the main determinant of plasmid tropism. PMID:24700815

  17. Genome degradation in Brucella ovis corresponds with narrowing of its host range and tissue tropism.

    Directory of Open Access Journals (Sweden)

    Renee M Tsolis

    Full Text Available Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis.

  18. Tissue tropism related to vector competence of Frankliniella occidentalis for tomato spotted wilt tospovirus.

    Science.gov (United States)

    Nagata, T; Inoue-Nagata, A K; Smid, H M; Goldbach, R; Peters, D

    1999-02-01

    The development of tomato spotted wilt tospovirus (TSWV) infection in the midgut and salivary glands of transmitting and non-transmitting thrips, Frankliniella occidentalis, was studied to elucidate tissue tropism and the virus pathway within the body of this vector. Immunohistological techniques used in this study showed that the midgut, foregut and salivary glands were the only organs in which virus accumulated. The first signals of infection, observed as randomly distributed fluorescent granular spots, were found in the epithelial cells of the midgut, mainly restricted to the anterior region. The virus subsequently spread to the circular and longitudinal midgut muscle tissues, a process which occurred late in the larval stage. In the adult stage, the infection occurred in the visceral muscle tissues, covering the whole midgut and foregut, and was abolished in the midgut epithelium. The infection of the salivary glands was first observed 72 h post-acquisition, and simultaneously in the ligaments connecting the midgut with these glands. The salivary glands of transmitting individuals appeared heavily or completely infected, while no or only a low level of infection was found in the glands of non-transmitting individuals. Moreover, the development of an age-dependent midgut barrier against virus infection was observed in second instar larvae and adults. The results show that the establishment of TSWV infection in the various tissues and the potential of transmission seems to be regulated by different barriers and processes related to the metamorphosis of thrips.

  19. Natural Hendra Virus Infection in Flying-Foxes - Tissue Tropism and Risk Factors.

    Directory of Open Access Journals (Sweden)

    Lauren K Goldspink

    Full Text Available Hendra virus (HeV is a lethal zoonotic agent that emerged in 1994 in Australia. Pteropid bats (flying-foxes are the natural reservoir. To date, HeV has spilled over from flying-foxes to horses on 51 known occasions, and from infected horses to close-contact humans on seven occasions. We undertook screening of archived bat tissues for HeV by reverse transcription quantitative polymerase chain reaction (RT-qPCR. Tissues were tested from 310 bats including 295 Pteropodiformes and 15 Vespertilioniformes. HeV was detected in 20 individual flying-foxes (6.4% from various tissues including spleen, kidney, liver, lung, placenta and blood components. Detection was significantly higher in Pteropus Alecto and P. conspicillatus, identifying species as a risk factor for infection. Further, our findings indicate that HeV has a predilection for the spleen, suggesting this organ plays an important role in HeV infection. The lack of detections in the foetal tissues of HeV-positive females suggests that vertical transmission is not a regular mode of transmission in naturally infected flying-foxes, and that placental and foetal tissues are not a major source of infection for horses. A better understanding of HeV tissue tropism will strengthen management of the risk of spillover from flying-foxes to horses and ultimately humans.

  20. Natural Hendra Virus Infection in Flying-Foxes - Tissue Tropism and Risk Factors.

    Science.gov (United States)

    Goldspink, Lauren K; Edson, Daniel W; Vidgen, Miranda E; Bingham, John; Field, Hume E; Smith, Craig S

    2015-01-01

    Hendra virus (HeV) is a lethal zoonotic agent that emerged in 1994 in Australia. Pteropid bats (flying-foxes) are the natural reservoir. To date, HeV has spilled over from flying-foxes to horses on 51 known occasions, and from infected horses to close-contact humans on seven occasions. We undertook screening of archived bat tissues for HeV by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Tissues were tested from 310 bats including 295 Pteropodiformes and 15 Vespertilioniformes. HeV was detected in 20 individual flying-foxes (6.4%) from various tissues including spleen, kidney, liver, lung, placenta and blood components. Detection was significantly higher in Pteropus Alecto and P. conspicillatus, identifying species as a risk factor for infection. Further, our findings indicate that HeV has a predilection for the spleen, suggesting this organ plays an important role in HeV infection. The lack of detections in the foetal tissues of HeV-positive females suggests that vertical transmission is not a regular mode of transmission in naturally infected flying-foxes, and that placental and foetal tissues are not a major source of infection for horses. A better understanding of HeV tissue tropism will strengthen management of the risk of spillover from flying-foxes to horses and ultimately humans.

  1. Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

    Science.gov (United States)

    Song, MeiJuan; Zhang, XiuWei; Sun, ShuLi; Xiao, PeiXin; Hou, ShiKe; Ding, Hui; Liu, ZiQuan; Dong, WenLong; Wang, JinQiang; Wang, Xue; Sun, ZhiGuang

    2016-01-01

    Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells. PMID:27725837

  2. Ground-based studies of tropisms in hardware developed for the European Modular Cultivation System (EMCS)

    Science.gov (United States)

    Correll, Melanie J.; Edelmann, Richard E.; Hangarter, Roger P.; Mullen, Jack L.; Kiss, John Z.

    Phototropism and gravitropism play key roles in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism, but red light induces positive phototropism in Arabidopsis roots. The blue-light response is controlled by the phototropins while the red-light response is mediated by the phytochrome family of photoreceptors. In order to better characterize root phototropism, we plan to perform experiments in microgravity so that this tropism can be more effectively studied without the interactions with the gravity response. Our experiments are to be performed on the European Modular Cultivation System (EMCS), which provides an incubator, lighting system, and high resolution video that are on a centrifuge palette. These experiments will be performed at μg, 1g (control) and fractional g-levels. In order to ensure success of this mission on the International Space Station, we have been conducting ground-based studies on growth, phototropism, and gravitropism in experimental unique equipment (EUE) that was designed for our experiments with Arabidopsis seedlings. Currently, the EMCS and our EUE are scheduled for launch on space shuttle mission STS-121. This project should provide insight into how the blue- and red-light signaling systems interact with each other and with the gravisensing system.

  3. Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

    Directory of Open Access Journals (Sweden)

    MeiJuan Song

    2016-01-01

    Full Text Available Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs for treatment of acute lung injury (ALI. However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs in NOD/SCID mice with smoke inhalation injury (SII through bioluminescence imaging (BLI. The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

  4. Tricalcium phosphate nanoparticles enable rapid purification, increase transduction kinetics, and modify the tropism of mammalian viruses.

    Science.gov (United States)

    Dreesen, Imke A J; Lüchinger, Norman A; Stark, Wendelin J; Fussenegger, Martin

    2009-03-01

    Adenoviral, adeno-associated viral, and retroviral particles are chosen as gene delivery shuttles in more than 50% of all gene therapy clinical trials. Bulk availability of clinical-grade viral particles and their efficiency to transduce the therapeutic cargo into specific target cells remain the most critical bottlenecks in gene therapy applications to date. Capitalizing on the flame-spray technology for the reproducible economic large-scale production of amorphous tricalcium phosphate nanoparticulate powders (ATCP), we designed a scalable ready-to-use gravity-flow column set-up for the straightforward concentration and purification of transgenic adenoviral, adeno-associated viral, and lentiviral particles. Specific elution buffers enabled rapid release of viral particles from the ATCP matrix of the column and provided high-titer virus preparations in an unsurpassed period of time. The interaction of ATCP with adenoviral, adeno-associated viral, and lentiviral particles in solution increased the transduction kinetics of several mammalian cell lines in culture. The nanoparticles were also able to modify the tropism of murine leukemia virus (MLV) towards transduction of human cells. Based on these findings, we believe that the use of flame-spray tricalcium phosphate nanoparticles will lead to important progress in the development of future gene therapy initiatives.

  5. Characterization of tissue tropism determinants of adeno-associated virus type 1.

    Science.gov (United States)

    Hauck, Bernd; Xiao, Weidong

    2003-02-01

    Muscle is an attractive target for gene delivery because of its mass and because vectors can be delivered in a noninvasive fashion. Adeno-associated virus (AAV) has been shown to be effective for muscle-targeted gene transfer. Recent progress in characterization of AAV serotype 1 (AAV1) and AAV6 demonstrated that these two AAV serotypes are far more efficient in transducing muscle than is the traditionally used AAV2. Since all cis elements are identical in these vectors, the potential determinants for their differences in transducing muscle appear to be located within the AAV capsid proteins. In the present study, a series of AAV capsid mutants were generated to identify the major regions affecting AAV transduction efficiency in muscle. Replacement of amino acids 350 to 736 of AAV2 VP1 with the corresponding amino acids from VP1 of AAV1 resulted in a hybrid vector that behaved very similarly to AAV1 in vitro and in vivo in muscle. Characterization of additional mutants carrying smaller regions of the AAV1 VP1 amino acid sequence in the AAV2 capsid protein suggested that amino acids 350 to 430 of VP1 function as a major tissue tropism determinant. Further analysis showed that the heparin binding domain and the major antigenic determinants in the AAV capsid region were not necessary for the efficiency of AAV1 transduction of muscle.

  6. Mechanisms of HIV-1 Control.

    Science.gov (United States)

    Soliman, Mary; Srikrishna, Geetha; Balagopal, Ashwin

    2017-06-01

    HIV-1 infection is of global importance, and still incurs substantial morbidity and mortality. Although major pharmacologic advances over the past two decades have resulted in remarkable HIV-1 control, a cure is still forthcoming. One approach to a cure is to exploit natural mechanisms by which the host restricts HIV-1. Herein, we review past and recent discoveries of HIV-1 restriction factors, a diverse set of host proteins that limit HIV-1 replication at multiple levels, including entry, reverse transcription, integration, translation of viral proteins, and packaging and release of virions. Recent studies of intracellular HIV-1 restriction have offered unique molecular insights into HIV-1 replication and biology. Studies have revealed insights of how restriction factors drive HIV-1 evolution. Although HIV-1 restriction factors only partially control the virus, their importance is underscored by their effect on HIV-1 evolution and adaptation. The list of host restriction factors that control HIV-1 infection is likely to expand with future discoveries. A deeper understanding of the molecular mechanisms of regulation by these factors will uncover new targets for therapeutic control of HIV-1 infection.

  7. Expanding Thurston maps

    CERN Document Server

    Bonk, Mario

    2017-01-01

    This monograph is devoted to the study of the dynamics of expanding Thurston maps under iteration. A Thurston map is a branched covering map on a two-dimensional topological sphere such that each critical point of the map has a finite orbit under iteration. It is called expanding if, roughly speaking, preimages of a fine open cover of the underlying sphere under iterates of the map become finer and finer as the order of the iterate increases. Every expanding Thurston map gives rise to a fractal space, called its visual sphere. Many dynamical properties of the map are encoded in the geometry of this visual sphere. For example, an expanding Thurston map is topologically conjugate to a rational map if and only if its visual sphere is quasisymmetrically equivalent to the Riemann sphere. This relation between dynamics and fractal geometry is the main focus for the investigations in this work.

  8. Characteristics of human amniotic fluid mesenchymal stem cells and their tropism to human ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Liru Li

    Full Text Available The mesenchymal stem cells (MSCs derived from amniotic fluid (AF have become an attractive stem cells source for cell-based therapy because they can be harvested at low cost and avoid ethical disputes. In human research, stem cells derived from AF gradually became a hot research direction for disease treatment, specifically for their plasticity, their reduced immunogenicity and their tumor tropism regardless of the tumor size, location and source. Our work aimed to obtain and characterize human amniotic fluid mesenchymal stem cells (AFMSCs and detect their ovarian cancer tropsim in nude mice model. Ten milliliters of twenty independent amniotic fluid samples were collected from 16-20 week pregnant women who underwent amniocentesis for fetal genetic determination in routine prenatal diagnosis in the first affiliated hospital of Harbin medical university. We successfully isolated the AFMSCs from thirteen of twenty amniotic fluid samples. AFMSCs presented a fibroblastic-like morphology during the culture. Flow cytometry analyses showed that the cells were positive for specific stem cell markers CD73,CD90, CD105, CD166 and HLA-ABC (MHC class I, but negative for CD 45,CD40, CD34, CD14 and HLA-DR (MHC class II. RT-PCR results showed that the AFMSCs expressed stem cell marker OCT4. AFMSCs could differentiate into bone cells, fat cells and chondrocytes under certain conditions. AFMSCs had the high motility to migrate to ovarian cancer site but didn't have the tumorigenicity. This study enhances the possibility of AFMSCs as drug carrier in human cell-based therapy. Meanwhile, the research emphasis in the future can also put in targeting therapy of ovarian cancer.

  9. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes

    Directory of Open Access Journals (Sweden)

    Olson Ken E

    2007-01-01

    Full Text Available Abstract Background To be transmitted by its mosquito vector, dengue virus (DENV must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission. Results After ingestion of DENV-2, midgut infections in Chetumal mosquitoes were characterized by a peak in virus titers between 7 and 10 days post-infection (dpi. The amount of viral antigen and viral titers in the midgut then declined, but viral RNA levels remained stable. The presence of DENV-2 antigen in the trachea was positively correlated with virus dissemination from the midgut. DENV-2 antigen was found in salivary gland tissue in more than a third of mosquitoes at 4 dpi. Unlike in the midgut, the amount of viral antigen (as well as the percent of infected salivary glands increased with time. DENV-2 antigen also accumulated and increased in neural tissue throughout the EIP. DENV-2 antigen was detected in multiple tissues of the vector, but unlike some other arboviruses, was not detected in muscle. Conclusion Our results suggest that the EIP of DENV-2 in its vector may be shorter that the previously reported and that the tracheal system may facilitate DENV-2 dissemination from the midgut. Mosquito organs (e.g. midgut, neural tissue, and salivary glands differed in their response to DENV-2 infection.

  10. Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells.

    Science.gov (United States)

    Sayroo, R; Nolasco, D; Yin, Z; Colon-Cortes, Y; Pandya, M; Ling, C; Aslanidi, G

    2016-01-01

    Viral vectors-based gene therapy is an attractive alternative to common anti-cancer treatments. In the present studies, AAV serotype 6 vectors were identified to be particularly effective in the transduction of human prostate (PC3), breast (T47D) and liver (Huh7) cancer cells. Next, we developed chimeric AAV vectors with Arg-Gly-Asp (RGD) peptide incorporated into the viral capsid to enable specific targeting of integrin-overexpressing malignant cells. These AAV6-RGD vectors improved transduction efficiency approximately 3-fold compared with wild-type AAV6 vectors by enhancing the viral entry into the cells. We also observed that transduction efficiency significantly improved, up to approximately 5-fold, by the mutagenesis of surface-exposed tyrosine and threonine residues involved in the intracellular trafficking of AAV vectors. Therefore, in our study, the AAV6-Y705-731F+T492V vector was identified as the most efficient. The combination of RGD peptide, tyrosine and threonine mutations on the same AAV6 capsid further increased the transduction efficiency, approximately 8-fold in vitro. In addition, we mutated lysine (K531E) to impair the affinity of AAV6 vectors to heparan sulfate proteoglycan. Finally, we showed a significant increase in both specificity and efficiency of AAV6-RGD-Y705-731F+T492V+K531E vectors in a xenograft animal model in vivo. In summary, the approach described here can lead to the development of AAV vectors with selective tropism to human cancer cells.

  11. Evidence of vertical transmission and tissue tropism of Streptococcosis from naturally infected red tilapia (Oreochromis spp.

    Directory of Open Access Journals (Sweden)

    Padmaja Jayaprasad Pradeep

    2016-05-01

    Full Text Available Streptococcosis is a highly problematic disease in the aquaculture of freshwater fishes, especially for tilapia. The possibility of vertical transmission of streptococcosis and the pattern of tissue tropism of this pathogen in various organs was examined in red tilapia (Oreochromis sp.. Healthy broodstock without any clinical signs of Streptococcus spp. were selected from a farm earlier reported to have the disease and a total of 10 pairs were forced spawned to provide samples of gametes and progeny for pathogen testing. A colorimetric LAMP assay was used to confirm whether the bacterial pathogens Streptococcus. agalactiae and Streptococcus. iniae was present in samples of milt, unfertilized eggs, fertilized eggs, and offspring at various stages of development, as well as internal organs of broodstock (reproductive organs, gill, liver, spleen, kidney and brain as well as samples of water from culture systems. The majority of samples of milt (9/10 and unfertilized eggs (7/10 collected from the broodstock were infected with S. iniae at the time of spawning and was transmitted to all of their offspring. Nevertheless, when the same samples of gametes were analyzed for S. agalactiae, they were all found to be negative but the pathogen was found to be present in some 10-day-old larval offspring (4/10. However, when the pathogenic presence was analyzed from the reproductive organs of the parents, both S. agalactiae (11/20 and S. iniae (18/20 bacterium were common. Although, all broodstock were asymptomatic, almost all broodstock harboured the bacteria in many organs. Confirmation of vertical transmission of streptococcosis in tilapia means that intergenerational break cannot be used as a reliable and simple means of reducing or eliminating the prevalence of these difficult pathogens in aquaculture stock.

  12. The Times, They are a-Changing: HOPE for HIV-to-HIV Organ Transplantation.

    Science.gov (United States)

    Haidar, Ghady; Singh, Nina

    2017-09-01

    HIV-infected persons who achieve undetectable viral loads on antiretroviral therapy currently have near-normal lifespans. Liver disease is a major cause of non-AIDS-related deaths, and as a result of longer survival, the prevalence of end-stage renal disease in HIV is increasing. HIV-infected persons undergoing organ transplantation generally achieve comparable patient and graft survival rates compared to their HIV-uninfected counterparts, despite a nearly threefold increased risk of acute rejection. However, the ongoing shortage of suitable organs can limit transplantation as an option, and patients with HIV have higher waitlist mortality than others. One way to solve this problem would be to expand the donor pool to include HIV-infected individuals. The results of a South Africa study involving 27 HIV-to-HIV kidney transplants showed promise, with 3- and 5-year patient and graft survival rates similar to those of their HIV-uninfected counterparts. Similarly, individual cases of HIV-to-HIV liver transplantation from the United Kingdom and Switzerland have also shown good results. In the United States, HIV-to-HIV kidney and liver transplants are currently permitted only under a research protocol. Nevertheless, areas of ambiguity exist, including streamlining organ allocation practices, optimizing HIV-infected donor and recipient selection, managing donor-derived transmission of a resistant HIV strain, determining optimal immunosuppressive and antiretroviral regimens, and elucidating the incidence of rejection in HIV-to-HIV solid organ transplant recipients.

  13. Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Cutler Mary

    2010-11-01

    Full Text Available Abstract Background Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5α restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1 appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5α splice variant TRIM5δ in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction. Results We show that the interaction of BTBD1 and BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM producer cells. Additionally, interference with the expression of BTBD2 in AGM and human 293T target cells increased their permissiveness to HIV-1 infection two- to three-fold. Conclusions These results do not exclude the possibility that BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in cytoplasmic bodies.

  14. A framework to expand public services to children with biomedical ...

    African Journals Online (AJOL)

    The study undertook the development of a framework for expanding the public services available to children with biomedical healthcare needs related to HIV in South Africa. The study consisted of various component projects which were depicted as phases. The first phase was a descriptive quantitative analysis of ...

  15. Silicon microfabricated beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Othman, A., E-mail: aliman@ppinang.uitm.edu.my; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A. [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40450, Shah Alam, Selangor (Malaysia); Ain, M. F. [School of Electrical and Electronic Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300,Nibong Tebal, Pulau Pinang (Malaysia)

    2015-03-30

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  16. TRIPLE ACTION PALATE EXPANDER

    Directory of Open Access Journals (Sweden)

    Svetlana Yordanova

    2011-09-01

    Full Text Available Malocclusion correction essentially involves expansion of the maxilla, protrusion of anterior teeth and opening the bite. Expansion is often the stage preceding the treatment with fixed appliances. The elevation of the occlusion using accomplished with different devices (bite planes -fixed or removable, composite material on the occlusall surface of molars carries the risk of breaking or debonding them.The present article proposes an expanding appliance with triple action as a therapeutic means of choice in an orthodontic treatment with fixed appliances. The expander can simultaneously be used to protrude upper teeth, to expand the upper jaw and disarticulate the occlusion. It can be easily fabricated in clinical conditions, causes no discomfort and does not hamper oral hygiene because it can be removed and cleaned.

  17. Expandable gastroretentive dosage forms.

    Science.gov (United States)

    Klausner, Eytan A; Lavy, Eran; Friedman, Michael; Hoffman, Amnon

    2003-06-24

    Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3 decades. They were originally created for possible veterinary use, but later the design was modified for enhanced drug therapy in humans. These GRDFs are easily swallowed and reach a significantly larger size in the stomach due to swelling or unfolding processes that prolong their gastric retention time (GRT). After drug release, their dimensions are minimized with subsequent evacuation from the stomach. Gastroretentivity is enhanced by the combination of substantial dimensions with high rigidity of the dosage form to withstand the peristalsis and mechanical contractility of the stomach. Positive results were obtained in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow absorption window drugs compounded in such systems have improved in vivo absorption properties. These findings are an important step towards the implementation of expandable GRDFs in the clinical setting. The current review deals with expandable GRDFs reported in articles and patents, and describes the physiological basis of their design. Using the dog as a preclinical screening model prior to human studies, relevant imaging techniques and pharmacokinetic-pharmacodynamic aspects of such delivery systems are also discussed.

  18. Creating a National HIV Curriculum.

    Science.gov (United States)

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

    2016-01-01

    In recent years, the HIV care provider workforce has not kept pace with an expanding HIV epidemic. To effectively address this HIV workforce shortage, a multipronged approach is needed that includes high-quality, easily accessible, up-to-date HIV education for trainees and practicing providers. Toward this objective, the University of Washington, in collaboration with the AIDS Education and Training Center National Coordinating Resource Center, is developing a modular, dynamic curriculum that addresses the entire spectrum of the HIV care continuum. Herein, we outline the general principles, content, organization, and features of this federally funded National HIV Curriculum, which allows for longitudinal, active, self-directed learning, as well as real-time evaluation, tracking, and feedback at the individual and group level. The online curriculum, which is in development, will provide a free, comprehensive, interactive HIV training and resource tool that can support national efforts to expand and strengthen the United States HIV clinical care workforce. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  19. The role of cell signaling in poxvirus tropism: the case of the M-T5 host range protein of myxoma virus.

    Science.gov (United States)

    Werden, Steven J; McFadden, Grant

    2008-01-01

    Poxviruses demonstrate strict species specificity in vivo that range from narrow to broad, however the fundamental factors that mediate the basis of poxvirus tropism remain poorly understood. It is generally believed that most, if not all, poxviruses can efficiently bind and enter a wide range of mammalian cells and all of the known host anti-viral pathways that block viral replication in nonpremissive cells operate downstream of virus entry. A productive poxvirus infection is heavily dependent upon the production of a vast array of host modulatory products that specifically target and manipulate both extracellular immune response pathways of the host, as well as intracellular signal transduction pathways of the individually infected cells. The unique pathogenesis and host tropism of specific poxviruses can be attributed to the broad diversity of host modulatory proteins they express. Myxoma virus (MV) is a rabbit-specific poxviruses that encodes multiple host range factors, including an ankyrin-repeat protein M-T5, which functions to regulate tropism of MV for rabbit lymphocytes and some human cancer cells. At the molecular level, M-T5 binds and alters at least two distinct cellular proteins: Akt and cullin-1. The direct interaction between M-T5 and Akt was shown to be a key restriction determinant for MV tropism in a spectrum of human cancer cells making MV an excellent oncolytic candidate. Thus, the intricate relationship between viral encoded proteins and components of the host cell signaling networks can have profound impact on poxvirus tropism. The lessons we continue to learn from poxvirus host range factors like M-T5 will provide further insights into the factors that regulate poxvirus tropism and the mechanisms by which poxviruses micromanipulate the signaling pathways of the infected cell.

  20. Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

    Directory of Open Access Journals (Sweden)

    João Leandro de Paula Ferreira

    2008-12-01

    Full Text Available As in many areas of Brazil, the AIDS epidemic in Curitiba is relatively stable, but surveillance is important to support public policy. The molecular characteristics of HIV may be instrumental for monitoring epidemic trends. We evaluated plasma HIV-1 RNA (n = 37 from 38 cases presenting with positive serology, who were among 820 consenting volunteers visiting the downtown counselling and serology testing centre. Seroprevalence was 4.6% (CI 95% 3.2-6.3 and the estimated HIV incidence, as defined by the BED assay, was 2.86 persons/years (CI 95% 1.04-4.68. An additional set of contemporaneous, anonymous samples from a local laboratory was also analysed (n = 20. Regions of the HIV-1 polymerase (n = 57 and envelope (n = 34 were evaluated for subtyping, determination of mosaic structure, primary drug resistance mutations (pDRM, envelope V3 loop motifs and amino acid signatures related to viral tropism. HIV-1 clade B was observed in 53% of cases; HIV-1C in 30% and BC mosaics in 14%, with one F genome and one CF mosaic. Clade C infection was associated with recent infections among males (p < 0.03. Stanford surveillance pDRM was observed in 8.8% of sequences, with 7% showing high level resistance to at least one antiretroviral drug. Tropism for CXCR4 co-receptor was predicted in 18% of envelope sequences, which were exclusively among clade B genomes and cases with serological reactivity to chronic infection.

  1. HIV Prevention

    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 | ... Collapse All Is abstinence the only 100% effective HIV prevention option? Yes. Abstinence means not having oral, ...

  2. 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 ...

  3. Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain.

    Science.gov (United States)

    Alves, Sandro; Bode, Julia; Bemelmans, Alexis-Pierre; von Kalle, Christof; Cartier, Nathalie; Tews, Björn

    2016-06-20

    Recombinant adeno-associated viral (AAV) vectors have advanced to the vanguard of gene therapy. Numerous naturally occurring serotypes have been used to target cells in various tissues. There is a strong need for fast and dynamic methods which efficiently unravel viral tropism in whole organs. Ultramicroscopy (UM) is a novel fluorescence microscopy technique that images optically cleared undissected specimens, achieving good resolutions at high penetration depths while being non-destructive. UM was applied to obtain high-resolution 3D analysis of AAV transduction in adult mouse brains, especially in the hippocampus, a region of interest for Alzheimer's disease therapy. We separately or simultaneously compared transduction efficacies for commonly used serotypes (AAV9 and AAVrh10) using fluorescent reporter expression. We provide a detailed comparative and quantitative analysis of the transduction profiles. UM allowed a rapid analysis of marker fluorescence expression in neurons with intact projections deep inside the brain, in defined anatomical structures. Major hippocampal neuronal transduction was observed with both vectors, with slightly better efficacy for AAV9 in UM. Glial response and synaptic marker expression did not change post transduction.We propose UM as a novel valuable complementary tool to efficiently and simultaneously unravel tropism of different viruses in a single non-dissected adult rodent brain.

  4. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  5. Expandable LED array interconnect

    Science.gov (United States)

    Yuan, Thomas Cheng-Hsin; Keller, Bernd

    2011-03-01

    A light emitting device that can function as an array element in an expandable array of such devices. The light emitting device comprises a substrate that has a top surface and a plurality of edges. Input and output terminals are mounted to the top surface of the substrate. Both terminals comprise a plurality of contact pads disposed proximate to the edges of the substrate, allowing for easy access to both terminals from multiple edges of the substrate. A lighting element is mounted to the top surface of the substrate. The lighting element is connected between the input and output terminals. The contact pads provide multiple access points to the terminals which allow for greater flexibility in design when the devices are used as array elements in an expandable array.

  6. Grazing incidence beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  7. Correlation between the Trofile test and virological response to a short-term maraviroc exposure in HIV-infected patients.

    Science.gov (United States)

    Genebat, Miguel; Ruiz-Mateos, Ezequiel; León, Juan A; González-Serna, Alejandro; Pulido, Ildefonso; Rivas, Inmaculada; Ferrando-Martínez, Sara; Sánchez, Berta; Muñoz-Fernández, Ma Angeles; Leal, Manuel

    2009-10-01

    The current validated assay to determine tropism of HIV variants is Trofile, which has some limitations. The aim of this work was to correlate the virological response to a short-term maraviroc exposure with Trofile. From 1 July 2008 to 1 March 2009, 34 consecutive HIV-infected patients with detectable viral load during the last 6 months began an 8 day exposure to maraviroc (MCT group); six HIV-infected patients without antiretroviral therapy received no treatment (control group). Plasma viral load was evaluated on days 0, 2, 5 and 8. Baseline Trofile was performed in MCT group patients. The maraviroc clinical test (MCT) was considered positive if viral load was undetectable (HIV-RNA copies/mL) or a reduction > or = 1 log(10) HIV-RNA copies/mL was achieved after 8 days of maraviroc exposure. Global concordance between MCT and Trofile was 93.5%. In patients with R5 virus according to Trofile, MCT was positive in 19/20 (concordance 95%); in patients with dual/mixed virus, MCT was negative in 10/11 (concordance 90.9%). An additional phenotypic tropism assay was performed in patients with discordance between MCT and Trofile, being concordant with MCT in both cases. Three patients showed a non-reportable Trofile result, and all of them achieved undetectability after MCT. A clinical approach like short-term maraviroc exposure could be an additional resource to genetic and phenotypic HIV tropism assays. This clinical approach shows high concordance with Trofile, and could allow patients with non-reportable results by Trofile to benefit from maraviroc therapy.

  8. Expanding the HAWC Observatory

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Johanna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-17

    The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

  9. 5. Sexual Behaviours and Vulnerabilities to HIV

    African Journals Online (AJOL)

    Esem

    counseling and testing while expanding treatment for HIV and sexually transmitted infections. INTRODUCTION. 8states that there is a real need to understand the issue of HIV/AIDS in disabled people in global terms and to design and implement programmes and policy in a more coherent and comprehensive manner. The.

  10. Expanding the knowledge translation metaphor.

    Science.gov (United States)

    Engebretsen, Eivind; Sandset, Tony Joakim; Ødemark, John

    2017-03-13

    Knowledge translation (KT) is a buzzword in modern medical science. However, there has been little theoretical reflection on translation as a process of meaning production in KT. In this paper, we argue that KT will benefit from the incorporation of a more theoretical notion of translation as an entangled material, textual and cultural process. We discuss and challenge fundamental assumptions in KT, drawing on theories of translation from the human sciences. We show that the current construal of KT as separate from and secondary to the original scientific message is close to the now deeply compromised literary view of translation as the simple act of copying the original. Inspired by recent theories of translation, we claim that KT can be more adequately understood in terms of a 'double supplement' - on the one hand, KT offers new approaches to the communication of scientific knowledge to different groups in the healthcare system with the aim of supplementing a lack of knowledge among clinicians (and patients). On the other, it demonstrates that a textual and cultural supplement, namely a concern with target audiences (clinicians and patients), is inevitable in the creation of an 'autonomous' science. Hence, the division between science and its translation is unproductive and impossible to maintain. We discuss some possible implications of our suggested shift in concept by drawing on pharmaceutical interventions for the prevention of HIV as a case. We argue that such interventions are based on a supplementary and paradoxical relation to the target audiences, both presupposing and denying their existence. More sophisticated theories of translation can lay the foundation for an expanded model of KT that incorporates a more adequate and reflective description of the interdependency of scientific, cultural, textual and material practices.

  11. The expanding universe

    CERN Document Server

    Lew, Kristi

    2011-01-01

    People have always been fascinated with the stars above and the universe that contains them. Over the years, astronomers have developed numerous theories to explain how the universe began, how it works, and what its ultimate fate will be. But all of the scientists' questions are far from answered. The Expanding Universe goes beyond the creation of the universe to explain how scientists think the universe works, grows, and changes, including what great thinkers Isaac Newton and Albert Einstein had to say about its fate. Readers will also learn about how researchers are slowly shedding light on

  12. Expanding Your Horizon 2015

    CERN Multimedia

    Kaltenhauser, Kristin

    2015-01-01

    Expanding your horizons is a bi-annual “Science Day” for girls aged 11 to 14, held at the University of Geneva on 14 November. The girls had the opportunity to take part in hands-on workshops held by local professional women in the field of science, mathematics, engineering and technology. For the fourth time, CERN was part of this event, offering three workshops as well as a booth at the Discovery Fair, including Higgnite, an interactive visualization of the Higgs Field.

  13. 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.

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

    Science.gov (United States)

    Le Tortorec, Anna; Satie, Anne-Pascale; Denis, Hélène; Rioux-Leclercq, Nathalie; Havard, Laurence; Ruffault, Annick; Jégou, Bernard; Dejucq-Rainsford, Nathalie

    2008-12-31

    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. 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. 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.

  15. A putative marker for human pathogenic strains of Anaplasma phagocytophilum correlates with geography and host, but not human tropism.

    Science.gov (United States)

    Foley, Janet; Stephenson, Nicole; Cubilla, Michelle Pires; Qurollo, Barbara; Breitschwerdt, Edward B

    2016-03-01

    Anaplasma phagocytophilum is an Ixodes species tick-transmitted bacterium that is capable of infecting a variety of host species, although there is a diversity of bacterial strains with differing host tropism. Recent analysis of A. phagocytophilum strains suggested that "drhm", a gene locus designated "distantly related to human marker" (drhm), which was predicted to be an integral membrane protein with possible transporter functions was not present in available canine and human isolates. By assessing 117 strains from 14 host species from across the US, we extended this analysis. Phylogenetic clades were associated with geography, but not host species. Additionally, a virulent clade that lacks drhm and infects dogs, horses, and humans in northeastern US was identified. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission.

    Directory of Open Access Journals (Sweden)

    Nicolas Biteau

    2016-01-01

    Full Text Available Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T. b. gambiense 1135, causing a low level chronic 'silent' infection, was monitored in a murine model using bioluminescence imaging and PCR. A tropism to the reproductive organs, in addition to the central nervous system, after 12-18 months of infection was observed. Bioluminescent analysis of healthy females crossed with infected males showed that 50%, 62.5% and 37.5% of the female mice were subsequently positive for parasites in their ovaries, uteri and brain respectively. Although PCR confirmed the presence of parasites in the uterus of one of these mice, the blood of all mice was negative by PCR and LAMP. Subsequently, bioluminescent imaging of the offspring of infected female mice crossed with healthy males indicated parasites were present in the reproductive organs of both male (80% and female (60% offspring. These findings imply that transmission of T. b. gambiense 1135 occurs horizontally, most probably via sexual contact, and vertically in a murine model, which raises the possibility of a similar transmission in humans. This has wide reaching implications. Firstly, the observations made in this study are likely to be valid for wild animals acting as a reservoir for T. b. gambiense. Also, the reproductive organs may act as a refuge for parasites during drug treatment in a similar manner to the central nervous system. This could leave patients at risk of a relapse, ultimately allowing them to act as a reservoir for subsequent transmission by tsetse and possibly, horizontally and vertically.

  17. Pharmacological manipulation of the akt signaling pathway regulates myxoma virus replication and tropism in human cancer cells.

    Science.gov (United States)

    Werden, Steven J; McFadden, Grant

    2010-04-01

    Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells. The results of this study further characterize the mechanism by which M-T5 exploits the Akt signaling cascade and affirms this interaction as a major tropism determinant that regulates the replication efficiency of MYXV in human cancer cells.

  18. Pharmacological Manipulation of the Akt Signaling Pathway Regulates Myxoma Virus Replication and Tropism in Human Cancer Cells▿

    Science.gov (United States)

    Werden, Steven J.; McFadden, Grant

    2010-01-01

    Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells. The results of this study further characterize the mechanism by which M-T5 exploits the Akt signaling cascade and affirms this interaction as a major tropism determinant that regulates the replication efficiency of MYXV in human cancer cells. PMID:20106927

  19. Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes.

    Science.gov (United States)

    Wu, Zhijian; Asokan, Aravind; Grieger, Joshua C; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Samulski, R Jude

    2006-11-01

    Despite the high degree of sequence homology between adeno-associated virus (AAV) serotype 1 and 6 capsids (99.2%), these viruses have different liver transduction profiles when tested as vectors. Examination of the six amino acid residues that differ between AAV1 and AAV6 revealed that a lysine-to-glutamate change (K531E) suppresses the heparin binding ability of AAV6. In addition, the same mutation in AAV6 reduces transgene expression to levels similar to those achieved with AAV1 in HepG2 cells in vitro and in mouse liver following portal vein administration. In corollary, the converse E531K mutation in AAV1 imparts heparin binding ability and increases transduction efficiency. Extraction of vector genomes from liver tissue suggests that the lysine 531 residue assists in preferential transduction of parenchymal cells by AAV6 vectors in comparison with AAV1. Lysine 531 is unique to AAV6 among other known AAV serotypes and is located in a basic cluster near the spikes that surround the icosahedral threefold axes of the AAV capsid. Similar to studies with autonomous parvoviruses, this study describes the first example of single amino acid changes that can explain differential phenotypes such as viral titer, receptor binding, and tissue tropism exhibited by closely related AAV serotypes. In particular, a single lysine residue appears to provide the critical minimum charged surface required for interacting with heparin through electrostatic interaction and simultaneously plays an unrelated yet critical role in the liver tropism of AAV6 vectors.

  20. Expanding hollow metal rings

    Science.gov (United States)

    Peacock, Harold B [Evans, GA; Imrich, Kenneth J [Grovetown, GA

    2009-03-17

    A sealing device that may expand more planar dimensions due to internal thermal expansion of a filler material. The sealing material is of a composition such that when desired environment temperatures and internal actuating pressures are reached, the sealing materials undergoes a permanent deformation. For metallic compounds, this permanent deformation occurs when the material enters the plastic deformation phase. Polymers, and other materials, may be using a sealing mechanism depending on the temperatures and corrosivity of the use. Internal pressures are generated by either rapid thermal expansion or material phase change and may include either liquid or solid to gas phase change, or in the gaseous state with significant pressure generation in accordance with the gas laws. Sealing material thickness and material composition may be used to selectively control geometric expansion of the seal such that expansion is limited to a specific facing and or geometric plane.

  1. HIV Life Cycle

    Science.gov (United States)

    ... healthier lives. ART also reduces the risk of HIV transmission (the spread of HIV to others). HIV attacks and destroys ... lives. HIV medicines also reduce the risk of HIV transmission (the spread of HIV to others). What are the seven ...

  2. 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 ...

  3. Treatment for HIV

    Science.gov (United States)

    ... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

  4. Expander chunked codes

    Science.gov (United States)

    Tang, Bin; Yang, Shenghao; Ye, Baoliu; Yin, Yitong; Lu, Sanglu

    2015-12-01

    Chunked codes are efficient random linear network coding (RLNC) schemes with low computational cost, where the input packets are encoded into small chunks (i.e., subsets of the coded packets). During the network transmission, RLNC is performed within each chunk. In this paper, we first introduce a simple transfer matrix model to characterize the transmission of chunks and derive some basic properties of the model to facilitate the performance analysis. We then focus on the design of overlapped chunked codes, a class of chunked codes whose chunks are non-disjoint subsets of input packets, which are of special interest since they can be encoded with negligible computational cost and in a causal fashion. We propose expander chunked (EC) codes, the first class of overlapped chunked codes that have an analyzable performance, where the construction of the chunks makes use of regular graphs. Numerical and simulation results show that in some practical settings, EC codes can achieve rates within 91 to 97 % of the optimum and outperform the state-of-the-art overlapped chunked codes significantly.

  5. Quantifying the Antiviral Effect of IFN on HIV-1 Replication in Cell Culture

    Science.gov (United States)

    Ikeda, Hiroki; Godinho-Santos, Ana; Rato, Sylvie; Vanwalscappel, Bénédicte; Clavel, François; Aihara, Kazuyuki; Iwami, Shingo; Mammano, Fabrizio

    2015-06-01

    Type-I interferons (IFNs) induce the expression of hundreds of cellular genes, some of which have direct antiviral activities. Although IFNs restrict different steps of HIV replication cycle, their dominant antiviral effect remains unclear. We first quantified the inhibition of HIV replication by IFN in tissue culture, using viruses with different tropism and growth kinetics. By combining experimental and mathematical analyses, we determined quantitative estimates for key parameters of HIV replication and inhibition, and demonstrate that IFN mainly inhibits de novo infection (33% and 47% for a X4- and a R5-strain, respectively), rather than virus production (15% and 6% for the X4 and R5 strains, respectively). This finding is in agreement with patient-derived data analyses.

  6. The Artful Universe Expanded

    Science.gov (United States)

    Barrow, John D.

    2005-07-01

    Our love of art, writes John Barrow, is the end product of millions of years of evolution. How we react to a beautiful painting or symphony draws upon instincts laid down long before humans existed. Now, in this enhanced edition of the highly popular The Artful Universe , Barrow further explores the close ties between our aesthetic appreciation and the basic nature of the Universe. Barrow argues that the laws of the Universe have imprinted themselves upon our thoughts and actions in subtle and unexpected ways. Why do we like certain types of art or music? What games and puzzles do we find challenging? Why do so many myths and legends have common elements? In this eclectic and entertaining survey, Barrow answers these questions and more as he explains how the landscape of the Universe has influenced the development of philosophy and mythology, and how millions of years of evolutionary history have fashioned our attraction to certain patterns of sound and color. Barrow casts the story of human creativity and thought in a fascinating light, considering such diverse topics as our instinct for language, the origins and uses of color in nature, why we divide time into intervals as we do, the sources of our appreciation of landscape painting, and whether computer-generated fractal art is really art. Drawing on a wide variety of examples, from the theological questions raised by St. Augustine and C.S. Lewis to the relationship between the pure math of Pythagoras and the music of the Beatles, The Artful Universe Expanded covers new ground and enters a wide-ranging debate about the meaning and significance of the links between art and science.

  7. Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1.

    Science.gov (United States)

    Ndegwa, S

    2007-12-01

    (1) Maraviroc belongs to a new class of antiretroviral drugs designed to block entry of HIV-1 into CD4+ T-cells via the CCR5 coreceptor. It is indicated for combination therapy in treatment-experienced adults infected with CCR5-tropic HIV-1 that is resistant to multiple antiretroviral agents. (2) Results from two randomized controlled trials (RCTs) indicate that in treatment experienced patients, maraviroc, combined with optimized background therapy (OBT), significantly decreases the level of HIV-1 RNA in the blood (viral load) when compared with OBT alone. The number of patients achieving undetectable viral loads and CD4+ cell count increases were also significantly higher in those receiving maraviroc. (3) Most patients experiencing treatment failure with maraviroc exhibit tropism changes from CCR5-tropic to CXCR4-using virus, but there is no evidence of disease progression. (4) Adverse effects reported with maraviroc include cough, fever, upper respiratory tract infections, rash, muscle and joint pain, abdominal pain, and postural hypotension (dizziness). No significant increases in cardiovascular events, hepatotoxicity, infections or malignancies have been reported with short-term maraviroc therapy. Several post-marketing studies will assess maraviroc's long-term safety for immune function, liver function, malignancy, cardiac events, and risks associated with changes in tropism. (5) Results from an ongoing trial in treatment naive patients suggest that maraviroc may not be superior in terms of viral suppression to standard therapy, but may significantly increase the number of CD4+ T-cells.

  8. Acute onset myopericarditis as unusual presentation of primary HIV infection.

    Science.gov (United States)

    Vandi, Giacomo; Calza, Leonardo; Girometti, Nicolò; Manfredi, Roberto; Musumeci, Giuseppina; Bon, Isabella; Re, Maria Carla

    2017-02-01

    A 30-year-old man was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography examination showed a ST segment elevation involving the lower-lateral leads. A trans-thoracic ultrasonography showed findings compatible with an acute myopericarditis. All performed serological testings excluded other recent infections with cardiac tropism. Among screening tests, a peripheral lymphocyte subset analysis was performed and an inversion of the CD4/CD8 ratio was found. Therefore, HIV testing was performed and proved positive for HIV-1 antibodies. The discovery of a primary HIV infection with involvement of a vital organ led us to start HAART. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy. During the following days, the clinical conditions of our patient improved, and a further heart ultrasonography documented a mild pericardial thickening as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis. The histopathologic studies revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with a recent myocarditis. At the real-time PCR analysis on bioptic sample, only HHV6 DNA and HIV-DNA were reactive. An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented can be referred to the recent primary HIV-infection.

  9. A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line.

    Science.gov (United States)

    Wooley, Dawn P; Sharma, Priyanka; Weinstein, John R; Kotha Lakshmi Narayan, Poornima; Schaffer, David V; Excoffon, Katherine J D A

    2017-12-01

    A directed evolution approach was used to select for Adeno-associated virus (AAV) capsids that would exhibit more tropism toward an HIV-1 producer T cell line with the long-term goal of developing improved gene transfer vectors. A library of AAV variants was used to infect H9 T cells previously infected or uninfected by HIV-1 followed by AAV amplification with wild-type adenovirus. Six rounds of biological selection were performed, including negative selection and diversification after round three. The H9 T cells were successfully infected with all three wild-type viruses (AAV, adenovirus, and HIV-1). Four AAV cap mutants best representing the small number of variants emerging after six rounds of selection were chosen for further study. These mutant capsids were used to package an AAV vector and subsequently used to infect H9 cells that were previously infected or uninfected by HIV-1. A quantitative polymerase chain reaction assay was performed to measure cell-associated AAV genomes. Two of the four cap mutants showed a significant increase in the amount of cell-associated genomes as compared to wild-type AAV2. This study shows that directed evolution can be performed successfully to select for mutants with improved tropism for a T cell line in the presence of HIV-1. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The Expanding Universe: Dark Energy

    Energy Technology Data Exchange (ETDEWEB)

    Lincoln, Don [Fermilab; Nord, Brian [Fermilab

    2014-09-01

    In 1998, observations of distant supernovae led physicists that not only was the universe expanding, but the expansion was speeding up. In this article, we describe the evidence for an expanding universe and describe what physicists and cosmologists have learned in the intervening years. The target audience for this article is high school physics teachers and college physics professors at teaching institutions.

  11. Phylogeny and morphology of Ovipleistophora diplostomuri n. sp. (Microsporidia) with a unique dual-host tropism for bluegill sunfish and the digenean parasite Posthodiplostomum minimum (Strigeatida).

    Science.gov (United States)

    Lovy, J; Friend, S E

    2017-07-12

    Microsporidia are diverse opportunistic parasites abundant in aquatic organisms with some species hyperparasitic in digenean parasites. In the current study, we describe a unique microsporidian parasite, Ovipleistophora diplostomuri n. sp. that has a tropism for both the bluegill sunfish Lepomis macrochirus, and its digenean parasite Posthodiplostomum minimum. Though the microsporidium first infects a fish, the subsequent infection causes hypertrophy of the metacercarial wall and degeneration of the P. minimum metacercariae within the fish tissue. Genetic analysis placed this species within Ovipleistophora and ultrastructural characteristics were consistent with the genus, including the presence of dimorphic spores within sporophorous vesicles. Meronts did not have a surface coat of dense material, which has been previously reported for the genus. This is the first Ovipleistophora species described that does not have a tropism for ovary. Genetics demonstrated that O. diplostomuri n. sp. groups closely within fish microsporidia and not other species known to be hyperparasitic in digeneans, suggesting that it evolved from fish-infecting microsporidians and developed a secondary tropism for a common and widespread digenean parasite. The high genetic identity to Ovipleistophora species demonstrates the close relationship of this unique microsporidian with other microsporidia that infect ovary.

  12. [Research on relationship between tissue quantitative distribution of 3H-Achyranthes bidentata ecdysterone and channel-tropism of herbal drugs in mice].

    Science.gov (United States)

    Wu, Mishan; Zhao, Suzhi; Ren, Lizhong; Wang, Ru; Bai, Xia; Han, Hongwei; Li, Bin; Chen, Huayue

    2011-11-01

    To study the relationship between tissue quantitative distribution and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and the channel-tropism of herbal drugs in mice. 3H-achyranthes bidentata ecdysterone was used as a tracer agent and injected into mice by the caudal vein. In 36 hours, the contents of the tracer agent of samples involving 9 different tracing phases and organ or tissue were determined in order to observe the dynamic quantitative distribution and excretion and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and to understand the channel-tropism of herbal drugs achyranthes bidentata. 3H-achyranthes bidentata ecdysterone of same organs in different tracing phases and the contents of 3H-achyranthes bidentata ecdysterone in same tracing phases of different organs were significantly different (Pdistributed, in the liver, kidney, adrenal gland, small intestine and lung. The concentration-time profiles of achyranthes bidentata ecdysterone in rats injected into mice by the caudal vein were shown to fit a two-compartment open model with half-lives of (778.65 +/- 12.36) min, the elimination of achyranthes bidentata ecdysterone from plasma was found to be in accord with linear kinetics. The above mentioned selective distribution of 3H-achyranthes bidentata ecdysterone basically coincides with the meridian affinity and zang fu selection of the traditional Chinese medicine drug Achyranthes bidentata. This study will provide a scientific basis for the channel-tropism of A. bidentata.

  13. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors.

    Science.gov (United States)

    Nathanson, J L; Yanagawa, Y; Obata, K; Callaway, E M

    2009-06-30

    Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.

  14. Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected.

    Science.gov (United States)

    Cumberworth, Stephanie L; Barrie, Jennifer A; Cunningham, Madeleine E; de Figueiredo, Daniely Paulino Gomes; Schultz, Verena; Wilder-Smith, Adrian J; Brennan, Benjamin; Pena, Lindomar J; Freitas de Oliveira França, Rafael; Linington, Christopher; Barnett, Susan C; Willison, Hugh J; Kohl, Alain; Edgar, Julia M

    2017-06-23

    The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences.

  15. The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status.

    Science.gov (United States)

    Kim, M; Williamson, C T; Prudhomme, J; Bebb, D G; Riabowol, K; Lee, P W K; Lees-Miller, S P; Mori, Y; Rahman, M M; McFadden, G; Johnston, R N

    2010-07-08

    Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

  16. Expanded HIV Screening Projected to Decrease Spread of the Virus

    Science.gov (United States)

    ... Hispanics or Latinos Inmates and Parolees International Populations LGBT Populations Low Income Populations Men Military and Veterans Native Hawaiians and Other Pacific Islanders New Substance Users Older Adults Parents People with Drug Use Disorders People with ...

  17. Mathematical Modeling of the HIV/Kaposi’s Sarcoma Coinfection Dynamics in Areas of High HIV Prevalence

    Directory of Open Access Journals (Sweden)

    E. Lungu

    2013-01-01

    k to below unity should be the goal for disease eradication. Provision of HAART is shown to provide dual benefit of reducing HIV spread and the risk of acquiring another fatal disease for HIV/AIDS patients. By providing treatment to 10% of the HIV population, about 87% of the AIDS population acquire protection against coinfection with HIV and Kaposi's Sarcoma (KS. Most sub-Sahara African countries already have programmes in place to screen HIV. Our recommendation is that these programmes should be expanded to include testing for HHV-8 and KS counseling.

  18. The emergence and evolution of HIV counselling in Zambia: a 25-year history

    NARCIS (Netherlands)

    Simbaya, J.; Moyer, E.

    2013-01-01

    HIV-related counselling practices have evolved since emerging in Zambia in 1987. Whereas, initially, the goal of HIV counselling was to provide psychological support to the dying and their families, as knowledge about HIV grew, counselling objectives expanded to include behavioural change,

  19. Realising Equality in Access to HIV Treatment for Vulnerable and ...

    African Journals Online (AJOL)

    This article examines the relevance of the concept of equality in improving access to HIV treatment for vulnerable and marginalised groups in Africa. The article argues that though modest achievements have been made in expanding access to HIV treatment for those in need in Africa, this expansion has concentrated on the ...

  20. Sexual Dysfunction among HIV Patients: Three Case Reports and ...

    African Journals Online (AJOL)

    This may affect individuals' quality of life, interpersonal relationships and HIV treatment. The sub-Saharan Africa (SSA) region is the epicentre of the HIV epidemic, majority of the patients being young (< 30 years old) and in long-term heterosexual relationships. With increased life expectancy due to expanded access to ...

  1. HIV-1 genetic variants in Kyrgyzstan

    Directory of Open Access Journals (Sweden)

    V Laga

    2012-11-01

    Full Text Available Objectives: During the last two decades, HIV-1 has been spreading rapidly in former Soviet Union republics including Kyrgyzstan. The current molecular monitoring of HIV-infection epidemic is carried out in Russia only with no or limited data from the other FSU countries. The aim of this work was to investigate the prevalence of HIV-1 genetic variants circulating in Kyrgyzstan. Methods: Blood collection from the HIV-infected patients was carried out by local specialists with the informed consent and the questionnaire was answered by each of the patients. The total number of samples was 100. The washed cell pellets were transferred to Moscow following with proviral DNA extraction, PCR amplification and gag, pol and env genes sequencing. The phylogenetic analysis of nucleotide sequences using neighbor-joining method was carried out by MEGA 3 program. The preliminary data were obtained in 22 samples isolated from PBMC of HIV-infected patients from Kyrgyzstan. Results: Among the samples studied 6 (27.3% samples belonged to a subtype CRF02_AG, 16 samples - to subtype A (A1. One of the samples belonging to CRF02_AG, probably, is a recombinant between CRF02_AG and A1. There was no major drug resistance mutations in the samples studied. The minor mutations were presented in small proportions: 1 in PR (L10I, 6 in RT (A62V - in 3 samples, V108G, E138A, Y181F, M184I, L210M - on one sample and 1 in IN (L74M. It was impossible to associate the distribution of mutations with HIV-1 genetic variant. The V3 loop (env gene in 17 samples was analyzed for tropism using geno2pheno program; all samples were found to be R5-viruses. Conclusion: The HIV-1 subtype A seems to dominate in Kyrgyzstan like in other FSU countries. The recombinant CRF02_AG epidemiologically linked to Uzbekistan is quite widespread. The rest of Kyrgyzstan collection is under investigation and the data will be refined soon.

  2. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam

    NARCIS (Netherlands)

    Thao, Vu P.; Le, Thuy; Török, Estee M.; Yen, Nguyen T. B.; Chau, Tran T. H.; Jurriaans, Suzanne; van Doorn, Rogier H.; de Jong, Menno D.; Farrar, Jeremy J.; Dunstan, Sarah J.

    2012-01-01

    Background: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. Methods: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a

  3. Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain.

    Science.gov (United States)

    Cearley, Cassia N; Vandenberghe, Luk H; Parente, Michael K; Carnish, Erin R; Wilson, James M; Wolfe, John H

    2008-10-01

    A wide diversity of adeno-associated virus (AAV) structural proteins uncovered from latent genomes in primate tissue has expanded the number of AAV vector serotypes, which can potentially confer unique cell tropism to the vector. We evaluated 17 of these vectors in the mouse brain using green fluorescent protein (GFP) as a reporter gene. A rapid initial evaluation was performed by neonatal lateral ventricle injections. Vectors made with capsids hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, and AAV9 for comparison were selected for further analysis based on their ability to transduce large numbers of cells and result in novel patterns of cell transduction. These vectors were injected into adult brains in four major structures (cortex, striatum, hippocampus, and thalamus), and all were found to transduce neurons. In addition, hu.32, hu.11, pi.2, hu.48R3, and rh.8 resulted in GFP expression in some astrocytes or oligodendrocytes. AAVs rh.8, pi.2, hu.32, and hu.11 also appeared to result in neuronal transport of the vector genome. Vector transport was studied by a single unilateral injection into the hippocampus and vector genome was found in projection sites of the hippocampus. These unique patterns of cell transduction expand the potential repertoire for targeting AAV vectors to selected subsets of brain cells.

  4. Tissue tropism and target cells of NSs-deleted rift valley fever virus in live immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Céline Gommet

    2011-12-01

    Full Text Available BACKGROUND: Rift Valley fever virus (RVFV causes disease in livestock and humans. It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals. Severe clinical cases are characterized by acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The dynamics of RVFV infection and the cell types infected in vivo are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: RVFV strains expressing humanized Renilla luciferase (hRLuc or green fluorescent protein (GFP were generated and inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal was observed primarily in the thymus, spleen and liver. Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus. The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis. The brain remained weakly luminescent throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV. The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes. Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time. CONCLUSIONS/SIGNIFICANCE: These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice. They demonstrate that bioluminescent and fluorescent viruses can shed new

  5. Tissue tropism and molecular characterization of a Japanese encephalitis virus strain isolated from pigs in southwest China.

    Science.gov (United States)

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-04-02

    Since September 2012, an epidemic has been spreading among swine in a pig farm located in Sichuan province, southwest China, which has resulted in abortion, stillbirth, and fetal mummification. The brains of stillborn pigs were collected and a previously unknown Japanese encephalitis virus (JEV), namely SCYA201201, was isolated. According to the results of agarose gel diffusion precipitation, indirect immunofluorescence analysis, neutralization testing, reverse transcription PCR (RT-PCR) amplification, and physical and chemical testing, the virus was conformed to have the characteristics of JEV. The virus titer in BHK-21 cells was 10(8.47)PFU/ml and the median lethal dose (LD50) to 3-week-old and 7-day-old mice was 1.99 log10 and 1.02 log10 PFU/LD50, respectively. The results of tissue tropism for mice showed that the viral load in the brain was significantly higher than other organs, indicating that the isolate was strongly neurotropic. Additionally, the complete genome sequence of the isolate was determined and compared with other JEV strains. Phylogenetic analysis showed that the isolate belongs to genotype I and may be an imported virus. The isolate had 88.4% nucleotide identity with the Chinese vaccine strain SA14-14-2. However, there were 69 amino acid substitutions compared with the strain SA14-14-2. Some substitutions indicated that SCYA201201 was highly neurovirulent and infective, in accordance with the results of animal testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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.

  7. Development of peptide inhibitors of HIV transmission

    Directory of Open Access Journals (Sweden)

    Siyu Shi

    2016-12-01

    Full Text Available Treatment of HIV has long faced the challenge of high mutation rates leading to rapid development of resistance, with ongoing need to develop new methods to effectively fight the infection. Traditionally, early HIV medications were designed to inhibit RNA replication and protein production through small molecular drugs. Peptide based therapeutics are a versatile, promising field in HIV therapy, which continues to develop as we expand our understanding of key protein-protein interactions that occur in HIV replication and infection. This review begins with an introduction to HIV, followed by the biological basis of disease, current clinical management of the disease, therapeutics on the market, and finally potential avenues for improved drug development.

  8. HIVBrainSeqDB: a database of annotated HIV envelope sequences from brain and other anatomical sites

    Directory of Open Access Journals (Sweden)

    O'Connor Niall

    2010-12-01

    Full Text Available Abstract Background The population of HIV replicating within a host consists of independently evolving and interacting sub-populations that can be genetically distinct within anatomical compartments. HIV replicating within the brain causes neurocognitive disorders in up to 20-30% of infected individuals and is a viral sanctuary site for the development of drug resistance. The primary determinant of HIV neurotropism is macrophage tropism, which is primarily determined by the viral envelope (env gene. However, studies of genetic aspects of HIV replicating in the brain are hindered because existing repositories of HIV sequences are not focused on neurotropic virus nor annotated with neurocognitive and neuropathological status. To address this need, we constructed the HIV Brain Sequence Database. Results The HIV Brain Sequence Database is a public database of HIV envelope sequences, directly sequenced from brain and other tissues from the same patients. Sequences are annotated with clinical data including viral load, CD4 count, antiretroviral status, neurocognitive impairment, and neuropathological diagnosis, all curated from the original publication. Tissue source is coded using an anatomical ontology, the Foundational Model of Anatomy, to capture the maximum level of detail available, while maintaining ontological relationships between tissues and their subparts. 44 tissue types are represented within the database, grouped into 4 categories: (i brain, brainstem, and spinal cord; (ii meninges, choroid plexus, and CSF; (iii blood and lymphoid; and (iv other (bone marrow, colon, lung, liver, etc. Patient coding is correlated across studies, allowing sequences from the same patient to be grouped to increase statistical power. Using Cytoscape, we visualized relationships between studies, patients and sequences, illustrating interconnections between studies and the varying depth of sequencing, patient number, and tissue representation across studies

  9. Expanding the Game Design Space

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel; Majgaard, Gunver

    2016-01-01

    . It encapsulates the entire development process from the first ideas to the final game with emphasis on game design thinking. Our model of expanded game design space consists of four separate – yet interconnected – layers in the process of game development. The first layer addresses the importance of framing...... as a guideline for evaluating game design thinking and for measuring solutions made in the development process. To strengthen our model of expanded design space, we will present examples from our game design courses.......This article considers game design research in educational settings. Its focus is on how undergraduate students – particularly engineering students – learn computer game design. From observations conducted during our game design courses we have developed a model of expanded game design space...

  10. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  11. Novel caprine adeno-associated virus (AAV) capsid (AAV-Go.1) is closely related to the primate AAV-5 and has unique tropism and neutralization properties.

    Science.gov (United States)

    Arbetman, Alejandra E; Lochrie, Michael; Zhou, Shangzhen; Wellman, Jennifer; Scallan, Ciaran; Doroudchi, Mohammad M; Randlev, Britta; Patarroyo-White, Susannah; Liu, Tongyao; Smith, Peter; Lehmkuhl, Howard; Hobbs, Lea Ann; Pierce, Glenn F; Colosi, Peter

    2005-12-01

    Preexisting humoral immunity to adeno-associated virus (AAV) vectors may limit their clinical utility in gene delivery. We describe a novel caprine AAV (AAV-Go.1) capsid with unique biological properties. AAV-Go.1 capsid was cloned from goat-derived adenovirus preparations. Surprisingly, AAV-Go.1 capsid was 94% identical to the human AAV-5, with differences predicted to be largely on the surface and on or under the spike-like protrusions. In an in vitro neutralization assay using human immunoglobulin G (IgG) (intravenous immune globulin [IVIG]), AAV-Go.1 had higher resistance than AAV-5 (100-fold) and resistance similar to that of AAV-4 or AAV-8. In an in vivo model, SCID mice were pretreated with IVIG to generate normal human IgG plasma levels prior to the administration of AAV human factor IX vectors. Protein expression after intramuscular administration of AAV-Go.1 was unaffected in IVIG-pretreated mice, while it was reduced 5- and 10-fold after administration of AAV-1 and AAV-8, respectively. In contrast, protein expression after intravenous administration of AAV-Go.1 was reduced 7.1-fold, similar to the 3.8-fold reduction observed after AAV-8 administration in IVIG-pretreated mice, and protein expression was essentially extinguished after AAV-2 administration in mice pretreated with much less IVIG (15-fold). AAV-Go.1 vectors also demonstrated a marked tropism for lung when administered intravenously in SCID mice. The pulmonary tropism and high neutralization resistance to human preexisting antibodies suggest novel therapeutic uses for AAV-Go.1 vectors, including targeting diseases such as cystic fibrosis. Nonprimate sources of AAVs may be useful to identify additional capsids with distinct tropisms and high resistance to neutralization by human preexisting antibodies.

  12. A Systems Biology Approach Reveals that Tissue Tropism to West Nile Virus Is Regulated by Antiviral Genes and Innate Immune Cellular Processes

    Science.gov (United States)

    Suthar, Mehul S.; Brassil, Margaret M.; Blahnik, Gabriele; McMillan, Aimee; Ramos, Hilario J.; Proll, Sean C.; Belisle, Sarah E.; Katze, Michael G.; Gale, Michael

    2013-01-01

    The actions of the RIG-I like receptor (RLR) and type I interferon (IFN) signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV). In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen) and nonpermissive (liver) tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs−/−×Ifnar−/− mice revealed the loss of expression of several key components within the natural killer (NK) cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs−/−×Ifnar−/− infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

  13. The Association of Benefit Finding to Psychosocial and Health Behavior Adaptation Among HIV+ Men and Women

    OpenAIRE

    Littlewood, Rae A.; Vanable, Peter A.; Carey, Michael P.; Blair, Donald C.

    2008-01-01

    Psychological and behavioral adaptation to HIV is integral to long-term survival. Although most research on coping with HIV has focused on factors associated with poor adaptation, recent research has expanded to include positive concomitants of adaptation, such as benefit finding. This study examined the occurrence of benefit finding among HIV+ men and women and evaluated the potential relevance of benefit finding to positive health behavior and psychosocial adaptation. HIV+ participants (N =...

  14. Genotypic and functional properties of early infant HIV-1 envelopes

    Directory of Open Access Journals (Sweden)

    Sullivan John L

    2011-08-01

    Full Text Available Abstract Background Understanding the properties of HIV-1 variants that are transmitted from women to their infants is crucial to improving strategies to prevent transmission. In this study, 162 full-length envelope (env clones were generated from plasma RNA obtained from 5 HIV-1 Clade B infected mother-infant pairs. Following extensive genotypic and phylogenetic analyses, 35 representative clones were selected for functional studies. Results Infant quasispecies were highly homogeneous and generally represented minor maternal variants, consistent with transmission across a selective bottleneck. Infant clones did not differ from the maternal in env length, or glycosylation. All infant variants utilized the CCR5 co-receptor, but were not macrophage tropic. Relatively high levels (IC50 ≥ 100 μg/ml of autologous maternal plasma IgG were required to neutralize maternal and infant viruses; however, all infant viruses were neutralized by pooled sera from HIV-1 infected individuals, implying that they were not inherently neutralization-resistant. All infant viruses were sensitive to the HIV-1 entry inhibitors Enfuvirtide and soluble CD4; none were resistant to Maraviroc. Sensitivity to human monoclonal antibodies 4E10, 2F5, b12 and 2G12 varied. Conclusions This study provides extensive characterization of the genotypic and functional properties of HIV-1 env shortly after transmission. We present the first detailed comparisons of the macrophage tropism of infant and maternal env variants and their sensitivity to Maraviroc, the only CCR5 antagonist approved for therapeutic use. These findings may have implications for improving approaches to prevent mother-to-child HIV-1 transmission.

  15. Flow boiling in expanding microchannels

    CERN Document Server

    Alam, Tamanna

    2017-01-01

    This Brief presents an up to date summary of details of the flow boiling heat transfer, pressure drop and instability characteristics; two phase flow patterns of expanding microchannels. Results obtained from the different expanding microscale geometries are presented for comparison and addition to that, comparison with literatures is also performed. Finally, parametric studies are performed and presented in the brief. The findings from this study could help in understanding the complex microscale flow boiling behavior and aid in the design and implementation of reliable compact heat sinks for practical applications.

  16. Transduction of brain dopamine neurons by adenoviral vectors is modulated by CAR expression: rationale for tropism modified vectors in PD gene therapy.

    Directory of Open Access Journals (Sweden)

    Travis B Lewis

    Full Text Available BACKGROUND: Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR. Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA neurons in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Ad5 was delivered to the substantia nigra (SN in wild type (wt and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the

  17. Tropism and toxicity of adeno-associated viral vector serotypes 1,2,5,6,7,8,9 in rat neurons and glia in vitro

    OpenAIRE

    Howard, Douglas B.; Powers, Kathleen; Wang, Yun; Harvey, Brandon K.

    2007-01-01

    Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene delivery to the central nervous system and are capable of transducing neurons and glia in vitro. In this study, seven serotypes of a rAAV vector expressing green fluorescent protein (GFP) were characterized for tropism and toxicity in primary cortical cells derived from embryonic rat brain. At 2 days after transduction, serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days post-transduction...

  18. Expanding nail or expanding femur? An adverse event with the expandable intramedullary nail.

    Science.gov (United States)

    Gangopadhyay, Soham; Riley, Nicholas D; Sivaji, Chellappan K

    2010-01-01

    The expandable intramedullary nail is self-locking and has the advantage of reducing operating time and exposure to ionizing radiation. The nail is recommended for simple diaphyseal fractures involving the middle third of long bones, where the nail can bypass the fracture site by at least 5 cm. We encountered a unique complication with the expandable nail in a simple transverse shaft fracture at the junction of the middle and distal third of the left femur in an otherwise healthy 57-year-old man. The fracture was reduced and a 12-mm expandable nail was inserted. Following full expansion, intraoperative radiographs were obtained prior to closure. After six postoperative weeks, it was noted that the nail expanded the femoral canal, converting a simple fracture to a distally progressing comminuted fracture with a butterfly fragment. A review of the intraoperative radiographs showed slight widening of the medullary canal at the level of the fracture. As the alignment was satisfactory and callus was present, no further surgical intervention was considered. The patient was advised not to bear weight and was provided with a locked knee brace in extension to wear for six weeks. Radiographs at 12 weeks demonstrated good progress of healing with adequate callus and the patient was permitted to bear weight as tolerated and commence knee flexion. The fracture united satisfactorily at four months. This adverse experience emphasizes that caution should be exercised when expanding the nail, with close observation of the medullary canal diameter during the later stages of expansion.

  19. Macrophage Tropism of Human Immunodeficiency Virus Type 1 Facilitates In Vivo Escape from Cytotoxic T-Lymphocyte Pressure

    Science.gov (United States)

    Schutten, M.; van Baalen, C. A.; Guillon, C.; Huisman, R. C.; Boers, P. H. M.; Sintnicolaas, K.; Gruters, R. A.; Osterhaus, A. D. M. E.

    2001-01-01

    Early after seroconversion, macrophage-tropic human immunodeficiency virus type 1 (HIV-1) variants are predominantly found, even when a mixture of macrophage-tropic and non-macrophage-tropic variants was transmitted. For virus contracted by sexual transmission, this is presently explained by selection at the port of entry, where macrophages are infected and T cells are relatively rare. Here we explore an additional mechanism to explain the selection of macrophage-tropic variants in cases where the mucosa is bypassed during transmission, such as blood transfusion, needle-stick accidents, or intravenous drug abuse. With molecularly cloned primary isolates of HIV-1 in irradiated mice that had been reconstituted with a high dose of human peripheral blood mononuclear cells, we found that a macrophage-tropic HIV-1 clone escaped more efficiently from specific cytotoxic T-lymphocyte (CTL) pressure than its non-macrophage-tropic counterpart. We propose that CTLs favor the selective outgrowth of macrophage-tropic HIV-1 variants because infected macrophages are less susceptible to CTL activity than infected T cells. PMID:11222694

  20. The lowest X4 Geno2Pheno false-positive rate is associated with greater CD4 depletion in HIV-1 infected patients.

    Science.gov (United States)

    Santoro, M M; Armenia, D; Fabeni, L; Santoro, M; Gori, C; Forbici, F; Svicher, V; Bertoli, A; Dori, L; Surdo, M; Balestra, E; Palamara, G; Girardi, E; Angarano, G; Andreoni, M; Narciso, P; Antinori, A; Ceccherini-Silberstein, F; Perno, C F

    2012-08-01

    Through this study we evaluated whether the HIV-1 tropism determined by genotypic analysis correlates with HIV-1 markers, such as CD4 cell count and plasma HIV-RNA. The analysis was performed on 1221 HIV-1 B-subtype infected patients with an available V3 sequence (all maraviroc naive). Of them, 532 were antiretroviral therapy (ART) naive and 689 ART experienced. Tropism determination was performed by using the geno2pheno (co-receptor) algorithm set at a false-positive rate (FPR) of 10% and 2%. Potential associations of FPR with CD4 cell count and viraemia were evaluated. Association of V3 mutations with genotypic-determined tropism was also evaluated according to different FPR ranges. About 26% of patients (either ART naive or ART experienced) were infected by X4-tropic viruses (using the classical 10% FPR cut-off). However, a significantly lower proportion of ART-naive patients had FPR ≤ 2% in comparison with ART-experienced patients (4.9% vs. 12.6%, respectively, p HIV-1 infection (with CD4 cell count ≤ 200 cells/mm(3)) was significantly greater in X4-infected patients, either ART-naive (OR (95% CI)), 4.2 (1.8-9.2); p 0.0006) or ART-experienced (2.3 (1.4-3.6); p 0.0003), with FPR set at 2% (but not at 10%). This finding was confirmed by multivariable logistic analysis. No relationship was found between viraemia and FPR ≤2%. Some X4-related mutations were significantly associated with FPR ≤2% (ART-naive patients, S11R, Y21V, G24K and G24R, p ≤0.001; ART-experienced patients, Y7K, S11R, H13Y, p ≤0.002). In conclusion, these findings show that within the context of genotypically-assessed CXCR4 tropism, FPR ≤2% defines (far better than 10%-FPR) a viral population associated with low CD4 rank, with potentially greater cytopathic effect, and with more advanced disease. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  1. EFFECT OF INCORPORATING EXPANDED POLYSTYRENE ...

    African Journals Online (AJOL)

    2012-11-03

    Nov 3, 2012 ... Abstract. Incorporating expanded polystyrene granules in concrete matrix can produce lightweight polystyrene aggregate concrete of various densities. Workability which is an important property of concrete, affects the rate of placement and the degree of compaction of concrete. Inadequate compaction.

  2. Expanding the eukaryotic genetic code

    Science.gov (United States)

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2013-01-22

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  3. Expanding the eukaryotic genetic code

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2017-02-28

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  4. Randomized, community-based pharmacy intervention to expand services beyond sale of sterile syringes to injection drug users in pharmacies in New York City.

    Science.gov (United States)

    Crawford, Natalie D; Amesty, Silvia; Rivera, Alexis V; Harripersaud, Katherine; Turner, Alezandria; Fuller, Crystal M

    2013-09-01

    Structural interventions may help reduce racial/ethnic disparities in HIV. In 2009 to 2011, we randomized pharmacies participating in a nonprescription syringe access program in minority communities to intervention (pharmacy enrolled and delivered HIV risk reduction information to injection drug users [IDUs]), primary control (pharmacy only enrolled IDUs), and secondary control (pharmacy did not engage IDUs). Intervention pharmacy staff reported more support for syringe sales than did control staff. An expanded pharmacy role in HIV risk reduction may be helpful.

  5. Get Tested for HIV

    Science.gov (United States)

    ... The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency virus. This is the virus that causes AIDS. There is no cure yet for HIV/AIDS, but there are treatments that can help ...

  6. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... that may be present in rare strains of HIV. The test may not detect a drug-resistant strain of ... Less Common Questions Related Content On This Site Tests: HIV Viral Load ; CD4 Count ; HIV Antibody and HIV ...

  7. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... antiretroviral drugs. With genotypic resistance testing, the genetic code of the HIV a person has been infected ...

  8. 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 ...

  9. 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 ...

  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 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 ...

  12. HIV and Rheumatic Disease

    Science.gov (United States)

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

  13. HIV 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: January 18, 2018 ...

  14. 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 ( ...

  15. HIV/AIDS Coinfection

    Science.gov (United States)

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

  16. The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa

    NARCIS (Netherlands)

    J.A.C. Hontelez (Jan); S.J. de Vlas (Sake); R.M.P.M. Baltussen (Rob); M.-L. Newell (Marie-Louise); R. Bakker (Roel); F. Tanser (Frank); M.N. Lurie (Mark N.); T. Bärnighausen (Till)

    2012-01-01

    textabstractIntroduction: Antiretroviral treatment (ART) coverage is rapidly expanding in sub-Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission, the age composition of the HIV epidemic in the region is expected to change in the coming decades.

  17. The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa

    NARCIS (Netherlands)

    Hontelez, J.A.C.; Vlas, S.J. de; Baltussen, R.; Newell, M.L.; Bakker, R.; Tanser, F.; Lurie, M.; Barnighausen, T.

    2012-01-01

    INTRODUCTION: Antiretroviral treatment (ART) coverage is rapidly expanding in sub-Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission, the age composition of the HIV epidemic in the region is expected to change in the coming decades. We quantify

  18. Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro.

    Science.gov (United States)

    Howard, Douglas B; Powers, Kathleen; Wang, Yun; Harvey, Brandon K

    2008-03-01

    Recombinant adeno-associated viral (rAAV) vectors are frequently used for gene delivery to the central nervous system and are capable of transducing neurons and glia in vitro. In this study, seven serotypes of a rAAV vector expressing green fluorescent protein (GFP) were characterized for tropism and toxicity in primary cortical cells derived from embryonic rat brain. At 2 days after transduction, serotypes 1 and 5 through 8 expressed GFP predominately in glia, but by 6 days post-transduction expression was neuronal except for AAV5. AAV2 and 9 produced minimal GFP expression. Using cell viability assays, toxicity was observed at higher multiplicities of infection (MOI) for all serotypes except AAV2 and 9. The toxicity of AAV1 and 5-8 affected mostly glia as indicated by a loss of glial-marker immunoreactivity. A frameshift mutation in the GFP gene reduced overall toxicity for serotypes 1, 5 and 6, but not 7 and 8 suggesting that the toxicity was not solely due to the overexpression of GFP. Collectively, a differential tropism and toxicity was observed among the AAV serotypes on primary cortical cultures with an overall preferential glial transduction and toxicity.

  19. [HIV lipodystrophy].

    Science.gov (United States)

    Snopková, S; Matýsková, M; Povolná, K; Polák, P; Husa, P

    2010-12-01

    Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future.

  20. Drugs + HIV, Learn the Link

    Medline Plus

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

  1. Expanding the Game Design Space

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel; Majgaard, Gunver

    2016-01-01

    layer establishes correspondence between formal elements of computer games and the structure of problem-based creativity. It addresses how game design challenges should be formulated and how creative solutions can be measured. The fourth and final layer demonstrates how clear framing can act......This article considers game design research in educational settings. Its focus is on how undergraduate students – particularly engineering students – learn computer game design. From observations conducted during our game design courses we have developed a model of expanded game design space....... It encapsulates the entire development process from the first ideas to the final game with emphasis on game design thinking. Our model of expanded game design space consists of four separate – yet interconnected – layers in the process of game development. The first layer addresses the importance of framing...

  2. Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data

    Directory of Open Access Journals (Sweden)

    Rodrigo Pessôa

    2016-03-01

    Full Text Available The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1×4 HIV strains in 84 proviral DNA massively parallel sequencing “MPS” data from well-defined non-recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina. Of the 84 MPS data samples, 63 (75% were derived from donors with long-standing infection and 21 (25% were lacking stage information. HIV‐1 tropism was inferred using Geno2pheno (g2p [454] algorithm (FPR=1%, 2.5%, and 3.75%. Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5% participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3% of participants. Nine of the 63 (14.3% subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5% harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists.

  3. HIV Among Asians

    Science.gov (United States)

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

  4. Living with HIV

    Science.gov (United States)

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

  5. HIV among Transgender People

    Science.gov (United States)

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

  6. Impairments of Motor Function While Multitasking in HIV.

    Science.gov (United States)

    Kronemer, Sharif I; Mandel, Jordan A; Sacktor, Ned C; Marvel, Cherie L

    2017-01-01

    Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing). Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  7. Impairments of Motor Function While Multitasking in HIV

    Directory of Open Access Journals (Sweden)

    Cherie L. Marvel

    2017-04-01

    Full Text Available Human immunodeficiency virus (HIV became a treatable illness with the introduction of combination antiretroviral therapy (CART. As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND. The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing. Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  8. Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

    Science.gov (United States)

    Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

    2015-09-01

    Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

  9. Tropisms of AAV for subretinal delivery to the neonatal mouse retina and its application for in vivo rescue of developmental photoreceptor disorders.

    Directory of Open Access Journals (Sweden)

    Satoshi Watanabe

    Full Text Available BACKGROUND: Adeno-associated virus (AAV is well established as a vehicle for in vivo gene transfer into the mammalian retina. This virus is promising not only for gene therapy of retinal diseases, but also for in vivo functional analysis of retinal genes. Previous reports have shown that AAV can infect various cell types in the developing mouse retina. However, AAV tropism in the developing retina has not yet been examined in detail. METHODOLOGY/PRINCIPAL FINDINGS: We subretinally delivered seven AAV serotypes (AAV2/1, 2/2, 2/5, 2/8, 2/9, 2/10, and 2/11 of AAV-CAG-mCherry into P0 mouse retinas, and quantitatively evaluated the tropisms of each serotype by its infecting degree in retinal cells. After subretinal injection of AAV into postnatal day 0 (P0 mouse retinas, various retinal cell types were efficiently transduced with different AAVs. Photoreceptor cells were efficiently transduced with AAV2/5. Retinal cells, except for bipolar and Müller glial cells, were efficiently transduced with AAV2/9. Horizontal and/or ganglion cells were efficiently transduced with AAV2/1, AAV2/2, AAV2/8, AAV2/9 and AAV2/10. To confirm the usefulness of AAV-mediated gene transfer into the P0 mouse retina, we performed AAV-mediated rescue of the Cone-rod homeobox gene knockout (Crx KO mouse, which exhibits an outer segment formation defect, flat electroretinogram (ERG responses, and photoreceptor degeneration. We injected an AAV expressing Crx under the control of the Crx 2kb promoter into the neonatal Crx KO retina. We showed that AAV mediated-Crx expression significantly decreased the abnormalities of the Crx KO retina. CONCLUSION/SIGNIFICANCE: In the current study, we report suitable AAV tropisms for delivery into the developing mouse retina. Using AAV2/5 in photoreceptor cells, we demonstrated the possibility of gene replacement for the developmental disorder and subsequent degeneration of retinal photoreceptors caused by the absence of Crx.

  10. Tropisms of AAV for Subretinal Delivery to the Neonatal Mouse Retina and Its Application for In Vivo Rescue of Developmental Photoreceptor Disorders

    Science.gov (United States)

    Watanabe, Satoshi; Sanuki, Rikako; Ueno, Shinji; Koyasu, Toshiyuki; Hasegawa, Toshiaki; Furukawa, Takahisa

    2013-01-01

    Background Adeno-associated virus (AAV) is well established as a vehicle for in vivo gene transfer into the mammalian retina. This virus is promising not only for gene therapy of retinal diseases, but also for in vivo functional analysis of retinal genes. Previous reports have shown that AAV can infect various cell types in the developing mouse retina. However, AAV tropism in the developing retina has not yet been examined in detail. Methodology/Principal Findings We subretinally delivered seven AAV serotypes (AAV2/1, 2/2, 2/5, 2/8, 2/9, 2/10, and 2/11) of AAV-CAG-mCherry into P0 mouse retinas, and quantitatively evaluated the tropisms of each serotype by its infecting degree in retinal cells. After subretinal injection of AAV into postnatal day 0 (P0) mouse retinas, various retinal cell types were efficiently transduced with different AAVs. Photoreceptor cells were efficiently transduced with AAV2/5. Retinal cells, except for bipolar and Müller glial cells, were efficiently transduced with AAV2/9. Horizontal and/or ganglion cells were efficiently transduced with AAV2/1, AAV2/2, AAV2/8, AAV2/9 and AAV2/10. To confirm the usefulness of AAV-mediated gene transfer into the P0 mouse retina, we performed AAV-mediated rescue of the Cone-rod homeobox gene knockout (Crx KO) mouse, which exhibits an outer segment formation defect, flat electroretinogram (ERG) responses, and photoreceptor degeneration. We injected an AAV expressing Crx under the control of the Crx 2kb promoter into the neonatal Crx KO retina. We showed that AAV mediated-Crx expression significantly decreased the abnormalities of the Crx KO retina. Conclusion/Significance In the current study, we report suitable AAV tropisms for delivery into the developing mouse retina. Using AAV2/5 in photoreceptor cells, we demonstrated the possibility of gene replacement for the developmental disorder and subsequent degeneration of retinal photoreceptors caused by the absence of Crx. PMID:23335994

  11. EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells--a new option for the treatment of B-CLL.

    Directory of Open Access Journals (Sweden)

    Romana Ruiss

    Full Text Available gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL, rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.

  12. EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells--a new option for the treatment of B-CLL.

    Science.gov (United States)

    Ruiss, Romana; Jochum, Simon; Mocikat, Ralph; Hammerschmidt, Wolfgang; Zeidler, Reinhard

    2011-01-01

    gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.

  13. EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL

    Science.gov (United States)

    Ruiss, Romana; Jochum, Simon; Mocikat, Ralph; Hammerschmidt, Wolfgang; Zeidler, Reinhard

    2011-01-01

    gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies. PMID:22022385

  14. In vitro separation and expansion of CD4 lymphocytes from HIV-infected individuals without activation of HIV infection

    DEFF Research Database (Denmark)

    Nielsen, S D; Nielsen, Jens Ole; Hansen, J E

    1997-01-01

    In order to offer a gene therapy-based treatment against AIDS, it is likely to be necessary to harvest and culture CD4 cells from HIV-positive patients without activating the HIV infection. We have used a magnetic cell sorting (MACS) system to enrich CD4 cells. Using positive selection, CD4 cells...... expression and no loss of polyclonality. Only in two of six cultures were we able to detect HIV-antigen production, and using an LTR-PCR and an RT assay, we did not find activation of the HIV infection during the culture period. Thus, the method described separates and expands CD4 cells from HIV......-positive patients without activation of the HIV infection....

  15. The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the “Seed” and the “Soil”?

    Directory of Open Access Journals (Sweden)

    Jenny E. Chu

    2012-01-01

    Full Text Available Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs, has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly ineffective against metastatic breast cancer, likely due to the innate therapy resistance of CSCs and the complex interactions that occur between cancer cells and their metastatic microenvironments. A better understanding of these interactions is essential for the development of novel therapeutic targets for metastatic disease. This paper summarizes the characteristics of breast CSCs and their potential metastatic microenvironments. Furthermore, it raises the question of the existence of a CSC niche and highlights areas for future investigation.

  16. An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism.

    Directory of Open Access Journals (Sweden)

    Hao Song

    2016-01-01

    Full Text Available Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.

  17. Predominance of CRF63_02A1 and multiple patterns of unique recombinant forms of CRF63_A1 among individuals with newly diagnosed HIV-1 infection in Kemerovo Oblast, Russia.

    Science.gov (United States)

    Gashnikova, Natalya M; Zyryanova, Darya P; Astakhova, Ekaterina M; Ivlev, Vladimir V; Gashnikova, Maria P; Moskaleva, Natalya V; Aikin, Sergey S; Bulatova, Tatyana N; Pustylnikov, Sergey V; Bocharov, Evgeny F; Totmenin, Aleksey V

    2017-02-01

    Kemerovo Oblast (KO) has had the highest rate of HIV spread in Russia since 2011. The aim of this work was to study the genetic variation of HIV-1 in Kemerovo Oblast. Blood was sampled from a total of 91 HIV-positive antiretroviral-therapy-naïve individuals in 2013 (38) and 2015 (53). HIV-1 subtypes, pol gene drug resistance mutations, and viral tropism were analyzed. In 2013-2015, the prevalence of HIV-1 subtype A decreased in KO from 60.5 to 7.5 %. The samples collected in 2015 from the patients with newly diagnosed HIV demonstrate the current dominance of HIV-1 CRF63_02A1 (71.7 %) and HIV-1 URF63_A1 (20.8 %), their parental viruses being CRF63_02A1 and subtype A. The initially predominant genetic variant, HIV-1 subtype A, was replaced in KO. An unusually high incidence of HIV-1 unique recombinant forms is probably the result of HIV-1 CRF63_02A1 introduction in the group of injection drug users with the initial HIV-1 subtype A infection and the practice of risky behavior that promotes reinfection. HIV-1 CRF63_02A1, which recently emerged in Siberia, and its recombinant forms have an ever-increasing impact on the current HIV epidemic in Russia, making urgent the need for in-depth study of this HIV-1 genetic variant.

  18. A GFP expressing influenza A virus to report in vivo tropism and protection by a matrix protein 2 ectodomain-specific monoclonal antibody.

    Science.gov (United States)

    De Baets, Sarah; Verhelst, Judith; Van den Hoecke, Silvie; Smet, Anouk; Schotsaert, Michael; Job, Emma R; Roose, Kenny; Schepens, Bert; Fiers, Walter; Saelens, Xavier

    2015-01-01

    The severity of influenza-related illness is mediated by many factors, including in vivo cell tropism, timing and magnitude of the immune response, and presence of pre-existing immunity. A direct way to study cell tropism and virus spread in vivo is with an influenza virus expressing a reporter gene. However, reporter gene-expressing influenza viruses are often attenuated in vivo and may be genetically unstable. Here, we describe the generation of an influenza A virus expressing GFP from a tri-cistronic NS segment. To reduce the size of this engineered gene segment, we used a truncated NS1 protein of 73 amino acids combined with a heterologous dimerization domain to increase protein stability. GFP and nuclear export protein coding information were fused in frame with the truncated NS1 open reading frame and separated from each other by 2A self-processing sites. The resulting PR8-NS1(1-73)GFP virus was successfully rescued and replicated as efficiently as the parental PR8 virus in vitro and was slightly attenuated in vivo. Flow cytometry-based monitoring of cells isolated from PR8-NS1(1-73)GFP virus infected BALB/c mice revealed that GFP expression peaked on day two in all cell types tested. In particular respiratory epithelial cells and myeloid cells known to be involved in antigen presentation, including dendritic cells (CD11c+) and inflammatory monocytes (CD11b+ GR1+), became GFP positive following infection. Prophylactic treatment with anti-M2e monoclonal antibody or oseltamivir reduced GFP expression in all cell types studied, demonstrating the usefulness of this reporter virus to analyze the efficacy of antiviral treatments in vivo. Finally, deep sequencing analysis, serial in vitro passages and ex vivo analysis of PR8-NS1(1-73)GFP virus, indicate that this virus is genetically and phenotypically stable.

  19. Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo.

    Directory of Open Access Journals (Sweden)

    Leigh Zerboni

    2015-06-01

    Full Text Available Varicella zoster virus (VZV, a human alphaherpesvirus, causes varicella during primary infection. VZV reactivation from neuronal latency may cause herpes zoster, post herpetic neuralgia (PHN and other neurologic syndromes. To investigate VZV neuropathogenesis, we developed a model using human dorsal root ganglia (DRG xenografts in immunodeficient (SCID mice. The SCID DRG model provides an opportunity to examine characteristics of VZV infection that occur in the context of the specialized architecture of DRG, in which nerve cell bodies are ensheathed by satellite glial cells (SGC which support neuronal homeostasis. We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for SGC contributes to VZV-related ganglionopathy. Based on quantitative analyses of viral and cell protein expression in DRG tissue sections, we demonstrated that, whereas DRG neurons had an immature neuronal phenotype prior to implantation, subtype heterogeneity was observed within 20 weeks and SGC retained the capacity to maintain neuronal homeostasis longterm. Profiling VZV protein expression in DRG neurons showed that VZV enters peripherin+ nociceptive and RT97+ mechanoreceptive neurons by both axonal transport and contiguous spread from SGC, but replication in RT97+ neurons is blocked. Restriction occurs even when the SGC surrounding the neuronal cell body were infected and after entry and ORF61 expression, but before IE62 or IE63 protein expression. Notably, although contiguous VZV spread with loss of SGC support would be predicted to affect survival of both nociceptive and mechanoreceptive neurons, RT97+ neurons showed selective loss relative to peripherin+ neurons at later times in DRG infection. Profiling cell factors that were upregulated in VZV-infected DRG indicated that VZV infection induced marked pro-inflammatory responses, as well as proteins of the interferon pathway and neuroprotective responses. These neuropathologic changes

  20. Balancing efficiency, equity and feasibility of HIV treatment in South Africa

    DEFF Research Database (Denmark)

    Baltussen, Rob; Mikkelsen, Evelinn; Tromp, Noor

    2013-01-01

    South Africa, the country with the largest HIV epidemic worldwide, has been scaling up treatment since 2003 and is rapidly expanding its eligibility criteria. The HIV treatment programme has achieved significant results, and had 1.8 million people on treatment per 2011. Despite these achievements...... on the design of the present HIV treatment programme in South Africa can be considered suboptimal. We argue there are two fundamental reasons to this. First, while there is a rapidly growing evidence-base to guide priority setting decisions on HIV treatment, its included studies typically consider only one......, and holds large potential to improve HIV priority setting in South Africa....

  1. Awareness of HIV Status, Prevention Knowledge and Condom Use among People Living with HIV in Mozambique

    Science.gov (United States)

    Dokubo, E. Kainne; Shiraishi, Ray W.; Young, Peter W.; Neal, Joyce J.; Aberle-Grasse, John; Honwana, Nely; Mbofana, Francisco

    2014-01-01

    Objective To determine factors associated with HIV status unawareness and assess HIV prevention knowledge and condom use among people living with HIV/AIDS (PLHIV) in Mozambique. Design Cross-sectional household-based nationally representative AIDS Indicator Survey. Methods Analyses focused on HIV-infected adults and were weighted for the complex sampling design. We identified PLHIV who had never been tested for HIV or received their test results prior to this survey. Logistic regression was used to assess factors associated with HIV status unawareness. Results Of persons with positive HIV test results (N = 1182), 61% (95% confidence interval [CI] 57–65%) were unaware of their serostatus. Men had twice the odds of being unaware of their serostatus compared with women [adjusted odds ratio (aOR) 2.05, CI 1.40–2.98]. PLHIV in the poorest wealth quintile were most likely to be unaware of their serostatus (aOR 3.15, CI 1.09–9.12) compared to those in the middle wealth quintile. Most PLHIV (83%, CI 79–87%) reported not using a condom during their last sexual intercourse, and PLHIV who reported not using a condom during their last sexual intercourse were more likely to be unaware of their serostatus (aOR 2.32, CI 1.57–3.43) than those who used a condom. Conclusions Knowledge of HIV-positive status is associated with more frequent condom use in Mozambique. However, most HIV-infected persons are unaware of their serostatus, with men and persons in the poorest wealth quintile being more likely to be unaware. These findings support calls for expanded HIV testing, especially among groups less likely to be aware of their HIV status and key populations at higher risk for infection. PMID:25222010

  2. 78 FR 49755 - Renewal of Charter for the Presidential Advisory Council on HIV/AIDS

    Science.gov (United States)

    2013-08-15

    ...) provide global leadership in responding to the HIV pandemic and expand access to treatment, care, and... Library of Congress on July 27, 2013. Renewal of the PACHA charter gives authorization for the Council to...

  3. Prevalence of HIV infection and the correlates among homeless in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Abbas Ostad Taghi Zadeh

    2014-01-01

    Conclusions: This study supports the idea that injection drug use is contributing to the increased spread of HIV among Iranian homeless. Harm reduction programs should be expanded, particularly among homeless injection drug users.

  4. OCT Expanded Clinical Data Analysis

    Science.gov (United States)

    Van Baalen, Mary; Tafreshi, Ali; Patel, Nimesh; Young, Millennia; Mason, Sara; Otto, Christian; Samuels, Brian; Koslovsky, Matthew; Schaefer, Caroline; Taiym, Wafa; hide

    2017-01-01

    Vision changes identified in long duration space fliers has led to a more comprehensive clinical monitoring protocol. Optical Coherence Tomography (OCT) was recently implemented on board the International Space Station in 2013. NASA is collaborating with Heidelberg Engineering to expand our current OCT data analysis capability by implementing a volumetric approach. Volumetric maps will be created by combining the circle scan, the disc block scan, and the radial scan. This assessment may provide additional information about the optic nerve and further characterize changes related microgravity exposure. We will discuss challenges with collection and analysis of OCT data, present the results of this reanalysis and outline the potential benefits and limitations of the additional data.

  5. Preventive Ethics Through Expanding Education.

    Science.gov (United States)

    Ho, Anita; MacDonald, Lisa Mei-Hwa; Unger, David

    2016-03-01

    Healthcare institutions have been making increasing efforts to standardize consultation methodology and to accredit both bioethics training programs and the consultants accordingly. The focus has traditionally been on the ethics consultation as the relevant unit of ethics intervention. Outcome measures are studied in relation to consultations, and the hidden assumption is that consultations are the preferred or best way to address day-to-day ethical dilemmas. Reflecting on the data from an internal quality improvement survey and the literature, we argue that having general ethics education as a key function of ethics services may be more important in meeting the contemporaneous needs of acute care settings. An expanded and varied ethics education, with attention to the time constraints of healthcare workers' schedules, was a key recommendation brought forward by survey respondents. Promoting ethical reflection and creating a culture of ethics may serve to prevent ethical dilemmas or mitigate their effects.

  6. Expanding Human Cognition and Communication

    Energy Technology Data Exchange (ETDEWEB)

    Spohrer, Jim [IBM, North Castle, NY (United States); Pierce, Brian M. [Raytheon Co., Waltham, MA (United States); Murray, Cherry A. [Lucent Technologies, Murray Hill, NJ (United States); Golledge, Reginald G. [Univ. of California, Santa Barbara, CA (United States); Horn, Robert E. [Stanford Univ., CA (United States); Turkle, Sherry [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Yonas, Gerold [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Glicken Turnley, Jessica [Galisteo Consulting Group, Inc., Albuquerque, NM (United States); Pollack, Jordan [Brandeis Univ., Waltham, MA (United States); Burger, Rudy [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Robinett, Warren; Wilson, Larry Todd [Inst. of Electrical and Electronics Engineers (IEEE), Piscataway, NJ (United States); Bainbridge, W. S.; Canton, J.; Kuekes, P.; Loomis, J.; Penz, P.

    2013-01-01

    To be able to chart the most profitable future directions for societal transformation and corresponding scientific research, five multidisciplinary themes focused on major goals have been identified to fulfill the overall motivating vision of convergence described in the previous pages. The first, “Expanding Human Cognition and Communication,” is devoted to technological breakthroughs that have the potential to enhance individuals’ mental and interaction abilities. Throughout the twentieth century, a number of purely psychological techniques were offered for strengthening human character and personality, but evaluation research has generally failed to confirm the alleged benefits of these methods (Druckman and Bjork 1992; 1994). Today, there is good reason to believe that a combination of methods, drawing upon varied branches of converging science and technology, would be more effective than attempts that rely upon mental training alone.

  7. Expanding the Trilinos developer community.

    Energy Technology Data Exchange (ETDEWEB)

    Heroux, Michael Allen

    2010-10-01

    The Trilinos Project started approximately nine years ago as a small effort to enable research, development and ongoing support of small, related solver software efforts. The 'Tri' in Trilinos was intended to indicate the eventual three packages we planned to develop. In 2007 the project expanded its scope to include any package that was an enabling technology for technical computing. Presently the Trilinos repository contains over 55 packages covering a broad spectrum of reusable tools for constructing full-featured scalable scientific and engineering applications. Trilinos usage is now worldwide, and many applications have an explicit dependence on Trilinos for essential capabilities. Users come from other US laboratories, universities, industry and international research groups. Awareness and use of Trilinos is growing rapidly outside of Sandia. Members of the external research community are becoming more familiar with Trilinos, its design and collaborative nature. As a result, the Trilinos project is receiving an increasing number of requests from external community members who want to contribute to Trilinos as developers. To-date we have worked with external developers in an ad hoc fashion. Going forward, we want to develop a set of policies, procedures, tools and infrastructure to simplify interactions with external developers. As we go forward with multi-laboratory efforts such as CASL and X-Stack, and international projects such as IESP, we will need a more streamlined and explicit process for making external developers 'first-class citizens' in the Trilinos development community. This document is intended to frame the discussion for expanding the Trilinos community to all strategically important external members, while at the same time preserving Sandia's primary leadership role in the project.

  8. Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors.

    Directory of Open Access Journals (Sweden)

    Tsunefusa Hayashida

    Full Text Available The association between emergence of CXCR4-tropic HIV-1 variants (X4 variants and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. We tried to answer this question.HIV-1 env sequences around the V3 region were analyzed in serially stocked samples in order to determine whether X4 variants emerged before or after the fall in CD4+ T-cell count.The study subjects were five HIV-1-infected hemophiliac slow progressors. Deep sequencing around the HIV-1 env V3 region was conducted in duplicate. Tropism was predicted by geno2pheno [coreceptor] 2.5 with cutoff value of false positive ratio at <5%. When X4 variant was identified in the latest stocked sample before the introduction of antiretroviral therapy, we checked viral genotype in previously stocked samples to determine the time of emergence of X4 variants.Emergence of X4 variants was noted in two of the five patients when their CD4+ T-cell counts were still high. The rate of decrease of CD4+ T-cell count or of rise of HIV-1 load accelerated significantly after the emergence of X4 variants in these two cases. Phylogenetic analysis showed that these X4 variants emerged from CCR5-tropic HIV-1 viruses with several amino acid changes in the V3 region.The emergence of X4 variants preceded HIV-1 disease progression in two hemophiliac slow progressors.

  9. 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, ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

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

  11. Microbial Biofilms and Breast Tissue Expanders

    Directory of Open Access Journals (Sweden)

    Melissa J. Karau

    2013-01-01

    Full Text Available We previously developed and validated a vortexing-sonication technique for detection of biofilm bacteria on the surface of explanted prosthetic joints. Herein, we evaluated this technique for diagnosis of infected breast tissue expanders and used it to assess colonization of breast tissue expanders. From April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders, six (85.7% had positive cultures, one of which grew Propionibacterium species. Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3–20.7% without clinical evidence of infection also had positive cultures, 45 growing Propionibacterium species and ten coagulase-negative staphylococci. While vortexing-sonication can detect clinically infected breast tissue expanders, 16 percent of breast tissue expanders appear to be asymptomatically colonized with normal skin flora, most commonly, Propionibacterium species.

  12. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage

    DEFF Research Database (Denmark)

    Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John

    2014-01-01

    BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral th...

  13. HIV-1

    African Journals Online (AJOL)

    the two major issues of stopping the AIDS epidemic and reducing poverty are addressed. Nevertheless ... affected by the same HIV epidemic as the general adult population. The resulting high absentee rates due to .... Streptococcus pneumoniae and non~typhoidal Salmonella. In the case of a Herxheimer-type reaction, ...

  14. HIV-1

    African Journals Online (AJOL)

    Leaders of the world's most powerful countries recently agreed at the G8 Summit (July 22-23, 2000) to ..... way to reduce these early deaths by reducing this toxic reaction.22 Prospective controlled trials in the .... strong leadership, they need to acknowledge the link between tuberculosis and HIV, and they need to show a ...

  15. Get Tested for HIV

    Science.gov (United States)

    ... AIDS from other websites National Women and Girls HIV/AIDS Awareness Day Blog topics HIV and AIDS Breaking Down ... t Miss a Beat National Women and Girls HIV/AIDS Awareness Day National Women's Health Week Supporting Nursing Moms ...

  16. Asymptomatic HIV infection

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000682.htm Asymptomatic HIV infection To use the sharing features on this page, please enable JavaScript. Asymptomatic HIV infection is a phase of HIV/AIDS during which ...

  17. Cultural Practices and the HIV Epidemic in Swaziland: Student\\'s ...

    African Journals Online (AJOL)

    HIV/AIDS is the most devastating experience that Swaziland has had to face in her history. Since the first HIV/AIDS cases were reported in the early 80s, this epidemic has been expanding relentlessly, destroying peoples lives and seriously impacting negatively on the very fabric of society. Time and resources have been ...

  18. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel

    NARCIS (Netherlands)

    Gunthard, H.F.; Aberg, J.A.; Eron, J.J.; Hoy, J.F.; Telenti, A.; Benson, C.A.; Burger, D.M.; Cahn, P.; Gallant, J.E.; Glesby, M.J.; Reiss, P.; Saag, M.S.; Thomas, D.L.; Jacobsen, D.M.; Volberding, P.A.

    2014-01-01

    IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when

  19. Predictors of HIV self-testing among health workers at Nyeri ...

    African Journals Online (AJOL)

    Background: HIV self-testing is recognised as a possible option of expanding access to HIV testing and counselling (HTC). There is high demand for self testing among health workers. However, in many health facilities in Kenya, the rate of unregulated self-testing and factors influencing the practice remain unknown.

  20. Impact of HIV/AIDS mortality on South Africa's life expectancy and ...

    African Journals Online (AJOL)

    kemrilib

    SUMMARY. The study seeks to raise awareness and expand knowledge about the deleterious effect of. HIV/AIDS mortality on South Africa's life expectancy, a country with a relatively high. HIV/AIDS prevalence rate (19. percent). Using the multiple and associated single decrement life table techniques, the study estimates ...

  1. Impact of HIV/AIDS mortality on South Africa's life expectancy and ...

    African Journals Online (AJOL)

    The study seeks to raise awareness and expand knowledge about the deleterious effect of HIV/AIDS mortality on South Africa's life expectancy, a country with a relatively high HIV/AIDS prevalence rate (19. percent). Using the multiple and associated single decrement life table techniques, the study estimates the total ...

  2. HIV sero-conversion during late pregnancy – when to retest

    Directory of Open Access Journals (Sweden)

    Emma Kalk

    2013-06-01

    Full Text Available The South African National Prevention of Mother-to-Child Transmission of HIV programme has resulted in significant reductions in vertical transmission, but new infant HIV infections continue to occur. We present two cases of HIV seroconversion during late pregnancy, demonstrating the limitations of the current programme. These could be mitigated by expanding the programme to include maternal testing at delivery and at immunisation clinic visits as we pursue the elimination of mother-to-child transmission.

  3. HIV controllers exhibit enhanced frequencies of major histocompatibility complex class II tetramer+ Gag-specific CD4+ T cells in chronic clade C HIV-1 infection

    DEFF Research Database (Denmark)

    Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos

    2017-01-01

    = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = -0.5, P......Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility......, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P...

  4. Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

    Directory of Open Access Journals (Sweden)

    Lawrence J Tartaglia

    2016-02-01

    Full Text Available Simian-human immunodeficiency virus (SHIV challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

  5. Discovery of Uniformly Expanding Universe

    Directory of Open Access Journals (Sweden)

    Cahill R. T.

    2012-01-01

    Full Text Available Saul Perlmutter and the Brian Schmidt – Adam Riess teams reported that their Friedmann-model GR-based analysis of their supernovae magnitude-redshift data re- vealed a new phenomenon of “dark energy” which, it is claimed, forms 73% of the energy / matter density of the present-epoch universe, and which is linked to the further claim of an accelerating expansion of the universe. In 2011 Perlmutter, Schmidt and Riess received the Nobel Prize in Physics “for the discovery of the accelerating ex- pansion of the Universe through observations of distant supernovae”. Here it is shown that (i a generic model-independent analysis of this data reveals a uniformly expanding universe, (ii their analysis actually used Newtonian gravity, and finally (iii the data, as well as the CMB fluctuation data, does not require “dark energy” nor “dark matter”, but instead reveals the phenomenon of a dynamical space, which is absent from the Friedmann model.

  6. Expanding cosmic horizons of life

    Science.gov (United States)

    Wickramasinghe, Nalin C.; Narlikar, J. V.; Wickramasinghe, J. T.; Wainwright, Milton

    2003-02-01

    The conceptual boundaries of life are rapidly expanding far beyond the confines of our planet to encompass an ever-widening region of the universe. Complex organic molecules in interstellar dust and comets appear most plausibly to be biologically derived, or at least closely related spectroscopically and structurally to such material. A de novo origin of life from non-living material is reckoned to have so minuscule a probability that its occurrence once in the universe can be considered miracle enough. The widespread distribution of similar material (e.g with the characteristics of the diffuse infrared bands and 2175 absorption features) throughout the galaxy and in external galaxies adds weight to the theory of panspermia, where it is supposed that the components of life at a generic level are readily transferred from one place to another. Spectroscopic evidence consistent with life extends to redshifts z=0.5, and from elemental abundance studies alone (e.g, of C, O and metals) in distant galaxies the possibility of cosmic life extends to redshifts as high as z=3.

  7. HIV status and participation in HIV surveillance in the era of antiretroviral treatment: a study of linked population-based and clinical data in rural South Africa.

    Science.gov (United States)

    Bärnighausen, T; Tanser, F; Malaza, A; Herbst, K; Newell, M-L

    2012-08-01

    To examine whether HIV status affects participation in a population-based longitudinal HIV surveillance in the context of an expanding HIV treatment and care programme in rural South Africa. We regressed consent to participate in the HIV surveillance during the most recent fieldworker visit on HIV status (based on previous surveillance participation or enrollment in pre-antiretroviral treatment (pre-ART) care or ART in the local HIV treatment and care programme), controlling for sex, age and year of the visit (N = 25,940). We then repeated the regression using the same sample but, in one model, stratifying HIV-infected persons into three groups (neither enrolled in pre-ART care nor receiving ART; enrolled in pre-ART care but not receiving ART; receiving ART) and, in another model, additionally stratifying the group enrolled in pre-ART and the group receiving ART into those with CD4 count ≤ 200/μl (i.e. the ART eligibility threshold at the time) vs. those with CD4 count >200/μl. HIV-infected individuals were significantly less likely to consent to participate in the surveillance than HIV-uninfected individuals [adjusted odds ratio (aOR), 0.74; 95% confidence interval, 0.70-0.79, P 200/μl in both the group enrolled in pre-ART and the group receiving ART. As HIV test results are not made available to participants in the HIV surveillance, our findings agree with the hypothesis that HIV-infected persons are less likely than HIV-uninfected persons to participate in HIV surveillance because they fear the negative consequences of others learning about their HIV infection. Our results further suggest that the increased knowledge of HIV status that accompanies improved ART access can reduce surveillance participation of HIV-infected persons, but that this effect decreases after ART initiation, in particular in successfully treated patients. © 2012 Blackwell Publishing Ltd.

  8. [Applying the Modified Delphi Technique to Develop the Role of HIV Case Managers and Essential Nursing Competencies in HIV Care].

    Science.gov (United States)

    Ko, Nai-Ying; Hsieh, Chia-Yin; Chen, Yen-Chin; Tsai, Chen-Hsi; Liu, Hsiao-Ying; Liu, Li-Fang

    2015-08-01

    Since 2005, the Taiwan Centers for Disease Control (Taiwan CDC) initiated an HIV case management program in AIDS-designated hospitals to provide integrative services and risk-reduction counseling for HIV-infected individuals. In light of the increasingly complex and highly specialized nature of clinical care, expanding and improving competency-based professional education is important to enhance the quality of HIV/AIDS care. The aim of this study was to develop the essential competency framework for HIV care for HIV case managers in Taiwan. We reviewed essential competencies of HIV care from Canada, the United Kingdom, and several African countries and devised descriptions of the roles of case managers and of the associated core competencies for HIV care in Taiwan. The modified Delphi technique was used to evaluate the draft framework of these roles and core competencies. A total of 15 HIV care experts were invited to join the expert panel to review and rank the draft framework. The final framework consisted of 7 roles and 27 competencies for HIV case managers. In Round 1, only 3 items did not receive consensus approval from the experts. After modification based on opinions of the experts, 7 roles and 27 competencies received 97.06% consensus approval in Round 2 and were organized into the final framework for HIV case managers. These roles and associated core competencies were: HIV Care Expert (9 competencies), Communicator (1 competency), Collaborator (4 competencies), Navigator (2 competencies), Manager (4 competencies), Advocate (2 competencies), and Professional (5 competencies). The authors developed an essential competency framework for HIV care using the consensus of a multidisciplinary expert panel. Curriculum developers and advanced nurses and practitioners may use this framework to support developments and to ensure a high quality of HIV care.

  9. Non-communicable diseases and HIV care and treatment: models of integrated service delivery.

    Science.gov (United States)

    Duffy, Malia; Ojikutu, Bisola; Andrian, Soa; Sohng, Elaine; Minior, Thomas; Hirschhorn, Lisa R

    2017-08-01

    Non-communicable diseases (NCD) are a growing cause of morbidity in low-income countries including in people living with human immunodeficiency virus (HIV). Integration of NCD and HIV services can build upon experience with chronic care models from HIV programmes. We describe models of NCD and HIV integration, challenges and lessons learned. A literature review of published articles on integrated NCD and HIV programs in low-income countries and key informant interviews were conducted with leaders of identified integrated NCD and HIV programs. Information was synthesised to identify models of NCD and HIV service delivery integration. Three models of integration were identified as follows: NCD services integrated into centres originally providing HIV care; HIV care integrated into primary health care (PHC) already offering NCD services; and simultaneous introduction of integrated HIV and NCD services. Major challenges identified included NCD supply chain, human resources, referral systems, patient education, stigma, patient records and monitoring and evaluation. The range of HIV and NCD services varied widely within and across models. Regardless of model of integration, leveraging experience from HIV care models and adapting existing systems and tools is a feasible method to provide efficient care and treatment for the growing numbers of patients with NCDs. Operational research should be conducted to further study how successful models of HIV and NCD integration can be expanded in scope and scaled-up by managers and policymakers seeking to address all the chronic care needs of their patients. © 2017 John Wiley & Sons Ltd.

  10. Improving and expanding NGO programmes.

    Science.gov (United States)

    Mukhopadhyay, A

    1993-06-01

    India has massive problems and is in need of improving and expanding non governmental organization (NGO) programs by broadening the scope of NGO activities, identifying successful NGO activities, and by moving closer to the community to participate in their activities. The problems and experience in the last few decades indicate that with expansion bureaucratization takes place. The institution begins to depend on donors and follows donor-driven agendas. As more money is given by the government, many more so called GONGO or Government-NGO projects materialize. Another problem is that the government almost always approaches the NGOs for the implementation of a project, and there is complete lack of cooperation at the planning stage. The government is considering a loan from the World Bank and UNICEF to launch a mother and child health program, but there has not been any discussion with the dozens of people who have worked on issues concerning mother and child health issues for many years. There is a need to be more demanding of the government about the various programs that are implemented for the government. Very few NGO health and family welfare projects are run by ordinary nurses or ordinary Ayurvedic doctors under ordinary conditions. Since successful NGO work has to be extended to other parts of the country, they will have to be run by ordinary people with very ordinary resources. Over the years, the NGO community has become preoccupied with its own agenda. Today, despite very sophisticated equipment and infrastructure, they are not able to reach the 60,000-70,000 workers and employees. Some of the ideas with respect to the strengthens and weaknesses of community participation have to be shared. NGOs should include all the existing non governmental organizations throughout the country, and have a dialogue with other nongovernmental bodies such as trade unions. The challenge is to adjust the current agenda, prevailing style, and present way of operating and move

  11. Expanding the Interaction Equivalency Theorem

    Directory of Open Access Journals (Sweden)

    Brenda Cecilia Padilla Rodriguez

    2015-06-01

    Full Text Available Although interaction is recognised as a key element for learning, its incorporation in online courses can be challenging. The interaction equivalency theorem provides guidelines: Meaningful learning can be supported as long as one of three types of interactions (learner-content, learner-teacher and learner-learner is present at a high level. This study sought to apply this theorem to the corporate sector, and to expand it to include other indicators of course effectiveness: satisfaction, knowledge transfer, business results and return on expectations. A large Mexican organisation participated in this research, with 146 learners, 30 teachers and 3 academic assistants. Three versions of an online course were designed, each emphasising a different type of interaction. Data were collected through surveys, exams, observations, activity logs, think aloud protocols and sales records. All course versions yielded high levels of effectiveness, in terms of satisfaction, learning and return on expectations. Yet, course design did not dictate the types of interactions in which students engaged within the courses. Findings suggest that the interaction equivalency theorem can be reformulated as follows: In corporate settings, an online course can be effective in terms of satisfaction, learning, knowledge transfer, business results and return on expectations, as long as (a at least one of three types of interaction (learner-content, learner-teacher or learner-learner features prominently in the design of the course, and (b course delivery is consistent with the chosen type of interaction. Focusing on only one type of interaction carries a high risk of confusion, disengagement or missed learning opportunities, which can be managed by incorporating other forms of interactions.

  12. Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines

    Directory of Open Access Journals (Sweden)

    Rena C. Patel

    2017-05-01

    Conclusion: This controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how HIV-positive women and their partners choose contraceptives, as well as information from providers on how they present and counsel patients on contraceptive options are needed to help guide policy and service delivery. Lastly, greater collaboration between HIV and reproductive health experts at all levels are needed to develop successful strategies to ensure the best HIV and reproductive health outcomes for women living with HIV.

  13. Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population.

    Directory of Open Access Journals (Sweden)

    Wei Song

    Full Text Available Acquisition of human immunodeficiency virus type 1 (HIV-1 infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN partners of serodiscordant Zambian couples.We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles, in the HESN partner (age, gender, or in the couple (behavioral and clinical risk score. Few if any previously implicated class I markers were associated here with the rate of acquiring infection.A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in disease control.

  14. Disparate Associations of HLA Class I Markers with HIV-1 Acquisition and Control of Viremia in an African Population

    Science.gov (United States)

    Song, Wei; He, Dongning; Brill, Ilene; Malhotra, Rakhi; Mulenga, Joseph; Allen, Susan; Hunter, Eric; Tang, Jianming; Kaslow, Richard A.

    2011-01-01

    Background Acquisition of human immunodeficiency virus type 1 (HIV-1) infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant Zambian couples. Methodology/Principal Findings We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles), in the HESN partner (age, gender), or in the couple (behavioral and clinical risk score). Few if any previously implicated class I markers were associated here with the rate of acquiring infection. Conclusions/Significance A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in

  15. Cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals in Mexico.

    Science.gov (United States)

    Contreras-Hernandez, Iris; Becker, Debbie; Chancellor, Jeremy; Kühne, Felicitas; Mould-Quevedo, Joaquin; Vega, Gabriela; Marfatia, Shalaka

    2010-12-01

    Maraviroc is the first approved drug in a new class of antiretrovirals, the CCR5 antagonists. The objective of this study was to predict the long-term clinical impact and cost-effectiveness of maraviroc in treatment-experienced adults with HIV/AIDS in Mexico. The AntiRetroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican context to predict clinical and economic outcomes of treating with optimized background therapy (OBT) versus testing for viral tropism status and treating with OBT ± maraviroc accordingly in treatment-experienced adults in Mexico. Baseline characteristics and efficacy were from the MOTIVATE trials' screening cohort. Costs and population mortality data were specific to Mexico. Results were reported from the perspective of health care payers in 2008 Mexican pesos (converted to 2008 US$ in parentheses). Compared to treatment with OBT alone, treatment with OBT ± maraviroc contingent on tropism test result increased projected undiscounted life expectancy and discounted quality-adjusted life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429) per QALY gained. The ICER was somewhat lower when maraviroc was modeled in individuals susceptible to ≤ 2 components of OBT ($407,329; US$38,069), while the ICER was higher in individuals susceptible to ≥3 OBT components ($718,718; US$67,171). In treatment-experienced individuals with HIV/AIDS in Mexico, maraviroc may be cost-effective, particularly in individuals with limited options for active antiretroviral therapy (ART). © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

  16. Using HIV&AIDS statistics in pre-service Mathematics Education to integrate HIV&AIDS education.

    Science.gov (United States)

    van Laren, Linda

    2012-12-01

    In South Africa, the HIV&AIDS education policy documents indicate opportunities for integration across disciplines/subjects. There are different interpretations of integration/inclusion and mainstreaming HIV&AIDS education, and numerous levels of integration. Integration ensures that learners experience the disciplines/subjects as being linked and related, and integration is required to support and expand the learners' opportunities to attain skills, acquire knowledge and develop attitudes and values across the curriculum. This study makes use of self-study methodology where I, a teacher educator, aim to improve my practice through including HIV&AIDS statistics in Mathematics Education. This article focuses on how I used HIV&AIDS statistics to facilitate pre-service teacher reflection and introduce them to integration of HIV&AIDS education across the curriculum. After pre-service teachers were provided with HIV statistics, they drew a pie chart which graphically illustrated the situation and reflected on issues relating to HIV&AIDS. Three themes emerged from the analysis of their reflections. The themes relate to the need for further HIV&AIDS education, the changing pastoral role of teachers and the changing context of teaching. This information indicates that the use of statistics is an appropriate means of initiating the integration of HIV&AIDS education into the academic curriculum.

  17. HIV/AIDS Medicines - Multiple Languages

    Science.gov (United States)

    ... 2 - English MP4 Who should consider taking PrEP? - PrEP, part 2 - Русский (Russian) MP4 Healthy Roads Media Spanish (español) Expand Section HIV/AIDS Medicines: MedlinePlus Health Topic - English Medicinas para el VIH/SIDA: Tema de salud de MedlinePlus - español (Spanish) ...

  18. Comparison of HIV-1 drug resistance profiles generated from novel software applications for routine patient care

    Directory of Open Access Journals (Sweden)

    Dimitri Gonzalez

    2014-11-01

    Full Text Available Introduction: Clinical laboratories performing routine HIV-1 genotyping antiviral drug resistance (DR testing need reliable and up-to-date information systems to provide accurate and timely test results to optimize antiretroviral treatment in HIV-1-infected patients. Materials and Methods: Three software applications were used to compare DR profiles generated from the analysis of HIV-1 protease (PR and reverse transcriptase (RT gene sequences obtained by Sanger sequencing assay in 100 selected clinical plasma samples from March 2013 through May 2014. Interpretative results obtained from the Trugene HIV-1 Genotyping assay (TG; Guidelines v17.0 were compared with a newly FDA-registered data processing module (DPM v1.0 and the research-use-only ViroScore-HIV (VS software, both of which use the latest versions of Stanford HIVdb (SD v7.0 and geno2pheno (G2P v3.3 interpretive algorithms (IA. Differences among the DR interpretive algorithms were compared according to drug class (NRTI, NNRTI, PI and each drug. HIV-1 tropism and integrase inhibitor resistance were not evaluated (not available in TG. Results: Overall, only 17 of the 100 TG sequences obtained yielded equivalent DR profiles among all 3 software applications for every IA and for all drug classes. DPM and VS generated equivalent results with >99.9% agreement. Excluding AZT, DDI, D4T and rilpivirine (not available in G2P, ranges of agreement in DR profiles among the three IA (using the DPM are shown in Table 1. Conclusions: Substantial discrepancies (<75% agreement exist among the three interpretive algorithms for ETR, while G2P differed from TG and SD for resistance to TDF and TPV/r. Use of more than one DR interpretive algorithm using well-validated software applications, such as DPM v1.0 and VS, would enable clinical laboratories to provide clinically useful and accurate DR results for patient care needs.

  19. Prevalencia de infección por VIH en la población adulta en México: una epidemia en ascenso y expansión Prevalence of HIV infection among adult population in Mexico: an increasingly expanding epidemic

    Directory of Open Access Journals (Sweden)

    José Luis Valdespino

    2007-01-01

    Full Text Available OBJETIVO: ONUSIDA ha reconocido que calcular la magnitud de la infección por VIH en los planos nacional o regional es importante desde el punto de vista de la evaluación, planeación de programas y supervisión. Al adoptar esta recomendación, el propósito de este trabajo fue cuantificar la magnitud de la infección en la población general adulta mexicana a partir de los datos consignados en la ENSA 2000, la cual permitió determinar la prevalencia de infección por VIH en la población general y los principales factores relacionados. La disponibilidad de datos de la Encuesta Seroepidemiológica proveyó además la oportunidad de conocer las tendencias en el periodo entre las dos encuestas (1987-2000. MATERIAL Y MÉTODOS: Se seleccionó de manera aleatoria a 21 271 individuos de 20 años de edad o mayores, de ambos sexos, estudiados en la ENSA 2000 para IgG anti-VIH1/2 (ELISA, confirmados por inmunoelectrotransferencia, y los principales factores relacionados con seropositividad. Las muestras se procesaron en el Instituto Nacional de Salud Pública en 2005. RESULTADOS: La prevalencia para anticuerpos anti-VIH-1 fue de 0.25%. Los principales factores vinculados con la infección fueron las edades más jóvenes, sexo masculino, vivir en el Distrito Federal, escolaridad de licenciatura o mayor y ser soltero, divorciado o separado. CONCLUSIONES: La seroprevalencia en hombres adultos muestra un incremento de 10 veces en comparación con la encuesta nacional de 1987. Si bien la epidemia continúa concentrada en hombres que tienen relaciones sexuales con hombres, existe evidencia de diseminación a la población heterosexual.OBJECTIVE: UNAIDS has recognized that estimating HIV infection at a national or regional level is important for evaluation, program planning and advocacy. Following this recommendation, the purpose of this study was to estimate the magnitude of HIV infection prevalence among adults from the general population using information

  20. Efficacy of Structured Organizational Change Intervention on HIV Testing in Correctional Facilities.

    Science.gov (United States)

    Belenko, Steven; Visher, Christy; Pearson, Frank; Swan, Holly; Pich, Michele; O'Connell, Daniel; Dembo, Richard; Frisman, Linda; Hamilton, Leah; Willett, Jennifer

    2017-06-01

    This article presents findings from a multisite cluster randomized trial of a structured organizational change intervention for improving HIV testing services in jails and prisons. Matched pairs of prison and jail facilities were randomized to experimental and control conditions; all facilities received baseline training about best practices in HIV testing and other HIV services and selected an area of HIV services on which to focus improvement efforts. The experimental facilities formed local change teams and were provided external coaching based on the Network for the Improvement of Addiction Treatment (NIATx) process improvement model. Difference-indifference analyses indicate a significant relative increase in HIV testing in the experimental compared to the control condition. Meta-analyses across the matched pairs indicated a small to medium effect of increased testing overall. The results indicate that the local change team model can achieve significant increases in HIV testing in correctional facilities. Implications for HIV testing policies and challenges for expanding testing are discussed.

  1. Recombinant Salmonella enterica Serovar Typhimurium as a Vaccine Vector for HIV-1 Gag

    Directory of Open Access Journals (Sweden)

    Nyasha Chin'ombe

    2013-08-01

    Full Text Available The HIV/AIDS epidemic remains a global health problem, especially in Sub-Saharan Africa. An effective HIV-1 vaccine is therefore badly required to mitigate this ever-expanding problem. Since HIV-1 infects its host through the mucosal surface, a vaccine for the virus needs to trigger mucosal as well as systemic immune responses. Oral, attenuated recombinant Salmonella vaccines offer this potential of delivering HIV-1 antigens to both the mucosal and systemic compartments of the immune system. So far, a number of pre-clinical studies have been performed, in which HIV-1 Gag, a highly conserved viral antigen possessing both T- and B-cell epitopes, was successfully delivered by recombinant Salmonella vaccines and, in most cases, induced HIV-specific immune responses. In this review, the potential use of Salmonella enterica serovar Typhimurium as a live vaccine vector for HIV-1 Gag is explored.

  2. HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay.

    Science.gov (United States)

    Sunshine, Sara; Kirchner, Rory; Amr, Sami S; Mansur, Leandra; Shakhbatyan, Rimma; Kim, Michelle; Bosque, Alberto; Siliciano, Robert F; Planelles, Vicente; Hofmann, Oliver; Ho Sui, Shannan; Li, Jonathan Z

    2016-05-01

    Antiretroviral therapy (ART) is successful in the suppression of HIV but cannot target and eradicate the latent proviral reservoir. The location of retroviral integration into the human genome is thought to play a role in the clonal expansion of infected cells and HIV persistence. We developed a high-throughput targeted sequence capture assay that uses a pool of HIV-specific probes to enrich Illumina libraries prior to deep sequencing. Using an expanded clonal population of ACH-2 cells, we demonstrate that this sequence capture assay has an extremely low false-positive rate. This assay assessed four cellular models commonly used to study HIV latency and latency-reversing agents: ACH-2 cells, J-Lat cells, the Bcl-2-transduced primary CD4(+)model, and the cultured TCM(central memory) CD4(+)model. HIV integration site characteristics and genes were compared between these cellular models and to previously reported patient data sets. Across these cellular models, there were significant differences in integration site characteristics, including orientation relative to that of the host gene, the proportion of clonally expanded sites, and the proportion located within genic regions and exons. Despite a greater diversity of minority integration sites than expected in ACH-2 cells, their integration site characteristics consistently differed from those of the other models and from the patient samples. Gene ontology analysis of highly represented genes from the patient samples found little overlap with HIV-containing genes from the cell lines. These findings show that integration site differences exist among the commonly used cellular models of HIV latency and in comparison to integration sites found in patient samples. Despite the success of ART, currently there is no successful therapy to eradicate integrated proviruses. Cellular models of HIV latency are used to test the efficacy of latency-reversing agents, but it is unclear how well these models reflect HIV integration

  3. HIV dynamics linked to memory CD4+ T cell homeostasis.

    Science.gov (United States)

    Murray, John M; Zaunders, John; Emery, Sean; Cooper, David A; Hey-Nguyen, William J; Koelsch, Kersten K; Kelleher, Anthony D

    2017-01-01

    The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART. Dynamics slowed over the following 2 years so that total HIV DNA levels were equivalent to reported values for individuals after 10 years of ART. The mathematical model reproduced the multiphasic dynamics of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and CHI over 3 years of ART. Under these simulations, residual viremia originated from reactivated latently infected cells where most of these cells arose from clonal expansion within the resting phenotype. Since virion production from clonally expanded cells will not be affected by antiretroviral drugs, simulations of ART intensification had little impact on pVL. HIV DNA decay over the first year of ART followed the loss of activated memory cells (120 day half-life) while the 5.9 year half-life of total HIV DNA after this point mirrored the slower decay of resting memory cells. Simulations had difficulty reproducing the fast early HIV DNA dynamics, including 2-LTR levels peaking at week 12, and the later slow loss of total and 2-LTR HIV DNA, suggesting some ongoing infection. In summary, our modelling indicates that much of the dynamical behavior of HIV can be explained by its impact on memory CD4+ T cell homeostasis.

  4. 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.

  5. The evolutionary analysis of emerging low frequency HIV-1 CXCR4 using variants through time--an ultra-deep approach.

    Directory of Open Access Journals (Sweden)

    John Archer

    2010-12-01

    Full Text Available Large-scale parallel pyrosequencing produces unprecedented quantities of sequence data. However, when generated from viral populations current mapping software is inadequate for dealing with the high levels of variation present, resulting in the potential for biased data loss. In order to apply the 454 Life Sciences' pyrosequencing system to the study of viral populations, we have developed software for the processing of highly variable sequence data. Here we demonstrate our software by analyzing two temporally sampled HIV-1 intra-patient datasets from a clinical study of maraviroc. This drug binds the CCR5 coreceptor, thus preventing HIV-1 infection of the cell. The objective is to determine viral tropism (CCR5 versus CXCR4 usage and track the evolution of minority CXCR4-using variants that may limit the response to a maraviroc-containing treatment regimen. Five time points (two prior to treatment were available from each patient. We first quantify the effects of divergence on initial read k-mer mapping and demonstrate the importance of utilizing population-specific template sequences in relation to the analysis of next-generation sequence data. Then, in conjunction with coreceptor prediction algorithms that infer HIV tropism, our software was used to quantify the viral population structure pre- and post-treatment. In both cases, low frequency CXCR4-using variants (2.5-15% were detected prior to treatment. Following phylogenetic inference, these variants were observed to exist as distinct lineages that were maintained through time. Our analysis, thus confirms the role of pre-existing CXCR4-using virus in the emergence of maraviroc-insensitive HIV. The software will have utility for the study of intra-host viral diversity and evolution of other fast evolving viruses, and is available from http://www.bioinf.manchester.ac.uk/segminator/.

  6. Dermatomyositis and HIV

    Directory of Open Access Journals (Sweden)

    Mamata Chand

    2016-12-01

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

  7. 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.

  8. 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.

  9. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    Science.gov (United States)

    ... Find HIV Treatment Services HIV and Mental Health HIV and Nutrition and Food Safety Print This Fact Sheet Entire Series Related Content AIDSource | HIV Treatment: Side Effects Need Help? Call 1-800- ...

  10. Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection

    Science.gov (United States)

    Demers, Korey R.; Makedonas, George; Buggert, Marcus; Eller, Michael A.; Ratcliffe, Sarah J.; Goonetilleke, Nilu; Li, Chris K.; Eller, Leigh Anne; Rono, Kathleen; Maganga, Lucas; Nitayaphan, Sorachai; Kibuuka, Hannah; Routy, Jean-Pierre; Slifka, Mark K.; Haynes, Barton F.; Bernard, Nicole F.; Robb, Merlin L.; Betts, Michael R.

    2016-01-01

    The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection. PMID:27486665

  11. In vivo transduction of murine cerebellar Purkinje cells by HIV-derived lentiviral vectors.

    Science.gov (United States)

    Torashima, Takashi; Okoyama, Shigeo; Nishizaki, Tomoyuki; Hirai, Hirokazu

    2006-04-12

    Cerebellar Purkinje cells are key elements in motor learning and motor coordination, and therefore, it is important to clarify the mechanisms by which Purkinje cells integrate information and control cerebellar function. Gene transfer into neurons, followed by the assessment of the effects on neural function, is an effective approach for examining gene function. However, this method has not been used fully in the study of the cerebellum because adenovirus vectors, the vectors most commonly used for in vivo gene transfer, have very low affinity for Purkinje cells. In this study, we used a human immunodeficiency virus (HIV)-derived lentiviral vector and examined the transduction profile of the vector in the cerebellum. A lentiviral vector carrying the GFP gene was injected into the cerebellar cortex. Seven days after the injection, Purkinje cells were efficiently transduced without significant influence on the cell viability and synaptic functions. GFP was also expressed, though less efficiently, in other cortical interneurons and Bergmann glias. In contrast to reported findings with other viral vectors, no transduced cells were observed outside of the cerebellar cortex. Thus, when HIV-derived lentiviral vectors were injected into the cerebellar cortex, transduction was limited to the cells in the cerebellar cortex, with the highest tropism for Purkinje cells. These results suggest that HIV-derived lentiviral vectors are useful for the study of gene function in Purkinje cells as well as for application as a gene therapy tool for the treatment of diseases that affect Purkinje cells.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and the disease it causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can ... HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the beginning of the ...

  14. 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 ...

  15. 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- ...

  16. 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 ...

  17. 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 ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

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

  19. Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication.

    Science.gov (United States)

    Gong, W; Howard, O M; Turpin, J A; Grimm, M C; Ueda, H; Gray, P W; Raport, C J; Oppenheim, J J; Wang, J M

    1998-02-20

    Human immunodeficiency virus, type I (HIV-1) cell-type tropism is dictated by chemokine receptor usage: T-cell line tropic viruses use CXCR4, whereas monocyte tropic viruses primarily use CCR5 as fusion coreceptors. CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed and secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion. MCP-2 is also a member of the CC chemokine subfamily and has the capacity to interact with at least two receptors including CCR-1 and CCR2B. In an effort to further characterize the binding properties of MCP-2 on leukocytes, we observed that MCP-2, but not MCP-1, effectively competed with MIP-1beta for binding to monocytes, suggesting that MCP-2 may interact with CCR5. As predicted, MCP-2 competitively inhibited MIP-1beta binding to HEK293 cells stably transfected with CCR5 (CCR5/293 cells). MCP-2 also bound to and induced chemotaxis of CCR5/293 cells with a potency comparable with that of MIP-1beta. Confocal microscopy indicates that MCP-2 caused remarkable and dose-dependent internalization of CCR5 in CCR5/293 cells. Furthermore, MCP-2 inhibited the entry/replication of HIV-1ADA in CCR5/293 cells coexpressing CD4. These results indicated that MCP-2 uses CCR5 as one of its functional receptors and is an additional potent natural inhibitor of HIV-1.

  20. A comparison of skin expansion and contraction between one expander and two expanders: a preliminary study.

    Science.gov (United States)

    Zhang, Gan-lin; Zhang, Jin-ming; Ji, Chen-yang; Meng, Hong; Huang, Jian-hua; Luo, He-yuan; Zhang, Hua-sheng; Liu, Xiao-tao; Hong, Xiao-fang

    2013-12-01

    This study aimed to compare the difference between the skin expansion and contraction rates for an expanded flap with one versus two expanders. The study cohort comprised 24 cases of two overlapping expanders and 15 cases of a single implanted expander involving 22 patients. The method of "wet-cloth sampling" was applied to measure the expanded flap area and the initial unexpanded area and to calculate the skin expansion rate. Two points 5 cm apart in the center of the expanded flap were selected before the second surgical stage. After removal of the expander, the distance between the two fixed points was measured and recorded. The contraction rate of the expanded flap then was calculated. During the same period of expansion in the two groups (p = 0.06, >0.01), the skin expansion rate was 3.5 ± 0.9 % in the group with two overlapping expanders and 2.6 ± 0.6 % in the control group. The difference between the two groups was statistically significant (p = 0.002, 0.05). We fitted a linear regression model that was Y = 0.533 − 0.003X, where Y was the contraction rate of the expanded flap and X was the period of expansion. The contraction rate of the expanded flap was negatively correlated with the period of expansion. Compared with the traditional method of implanting a single expander, the new method of overlapping two expanders in a single cavity increased the skin expansion rate. The instantly expanded flap contraction rate did not differ significantly between the two groups, so the amount of expanded skin area absolutely increased. The clinical application of the new method is worth promoting. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  1. Rethinking Gender, Heterosexual Men, and Women's Vulnerability to HIV/AIDS

    Science.gov (United States)

    Hoffman, Susie; Dworkin, Shari L.

    2010-01-01

    Most HIV prevention literature portrays women as especially vulnerable to HIV infection because of biological susceptibility and men's sexual power and privilege. Conversely, heterosexual men are perceived as active transmitters of HIV but not active agents in prevention. Although the women's vulnerability paradigm was a radical revision of earlier views of women in the epidemic, mounting challenges undermine its current usefulness. We review the etiology and successes of the paradigm as well as its accruing limitations. We also call for an expanded model that acknowledges biology, gender inequality, and gendered power relations but also directly examines social structure, gender, and HIV risk for heterosexual women and men. PMID:20075321

  2. CD8 T cell persistence in treated HIV infection

    Science.gov (United States)

    Mudd, J. C.; Lederman, Michael M

    2014-01-01

    Purpose of review Many treated HIV infected persons maintain persistently high circulating CD8 T cell numbers, even after many years of therapy. Recent reports suggest that persistent CD8 T cell expansion is associated with higher risk of morbid non-AIDS events. Thus, assessing the mechanisms of CD8 T cell expansion and persistence may give insights into a feature of HIV disease that is clinically important. Recent findings Acute HIV infection is associated with activation and expansion of the CD8 T cell compartment. Expanded CD8 T cells persist throughout disease course and, in contrast to the plasticity that typically characterizes immune responses to most other pathogens, circulating CD8 T cell numbers do not normalize in many patients despite pharmacological suppression of HIV replication. We suspect that residual inflammation in treated HIV infection contributes to antigen-independent CD8 T cell expansion and persistence as most of these cells are not HIV-reactive. Summary Circulating CD8 T cell numbers remain abnormally elevated in many treated HIV-infected patients and this elevation is associated with adverse clinical events. Future studies will need to assess the mechanisms of CD8 T cell expansion and to define the role of CD8 lymphocytosis in the clinical course of treated HIV disease. PMID:25010897

  3. HIV integration sites and implications for maintenance of the reservoir.

    Science.gov (United States)

    Symons, Jori; Cameron, Paul U; Lewin, Sharon R

    2018-03-01

    To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear. Clones with identical integration sites harbouring defective provirus can accumulate in HIV-infected individuals on ART and defective proviruses can express RNA and produce protein. HIV integration sites differ in clonally expanded and nonexpanded cells and in latently and productively infected cells and this influences basal and inducible transcription. There is a growing number of cellular proteins that can alter the pattern of integration to favour latency. Understanding these pathways may identify new interventions to eliminate latently infected cells. Using advances in analysing HIV integration sites, T-cell proliferation of latently infected cells is thought to play a major role in HIV persistence. Clonal expansion has been demonstrated with both defective and intact viruses. Production of viral RNA and protein from defective viruses may play a role in driving chronic immune activation. The site of integration may determine the likelihood of proliferation and the degree of basal and induced transcription. Finally, host factors and gene expression at the time of infection may determine the integration site. Together these new insights may lead to novel approaches to elimination of latently infected cells.

  4. HIV/AIDS in Vancouver, British Columbia: a growing epidemic

    Science.gov (United States)

    McInnes, Colin W; Druyts, Eric; Harvard, Stephanie S; Gilbert, Mark; Tyndall, Mark W; Lima, Viviane D; Wood, Evan; Montaner, Julio SG; Hogg, Robert S

    2009-01-01

    The prevalence of HIV in Vancouver, British Columbia was subject to two distinct periods of rapid increase. The first occurred in the 1980s due to high incidence among men who have sex with men (MSM), and the second occurred in the 1990s due to high incidence among injection drug users (IDU). The purpose of this study was to estimate and model the trends in HIV prevalence in Vancouver from 1980 to 2006. HIV prevalence data were entered into the UNAIDS/WHO Estimation and Projection Package (EPP) where prevalence trends were estimated by fitting an epidemiological model to the data. Epidemic curves were fit for IDU, MSM, street-based female sex trade workers (FSW), and the general population. Using EPP, these curves were then aggregated to produce a model of Vancouver's overall HIV prevalence. Of the 505 000 people over the age of 15 that reside in Vancouver, 6108 (ranging from 4979 to 7237) were living with HIV in the year 2006, giving an overall prevalence of 1.21 percent (ranging from 0.99 to 1.43 percent). The subgroups of IDU and MSM account for the greatest proportion of HIV infections. Our model estimates that the prevalence of HIV in Vancouver is greater than one percent, roughly 6 times higher than Canada's national prevalence. These results suggest that HIV infection is having a relatively large impact in Vancouver and that evidence-based prevention and harm reduction strategies should be expanded. PMID:19265531

  5. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

    NARCIS (Netherlands)

    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

  6. Integrated syphilis/HIV screening in China: a qualitative analysis

    Directory of Open Access Journals (Sweden)

    Yin Yue-Pin

    2010-03-01

    Full Text Available Abstract Background The last decade has seen enormous advances in HIV treatment and care, but how to implement scaled up HIV testing, prevention, and treatment in low-income areas still presents a formidable public health challenge. South China faces expanding syphilis and sexually transmitted HIV epidemics, but health systems characteristics important for scaling up syphilis and HIV testing have not been defined. Methods A purposive sample to ensure public, private, and public-private hybrid STI clinic inclusion was selected in a South China city. Eight key informant interviews were conducted with the STI clinic manager, followed by eight focus group discussions with physicians. Data collection relied on a semi-structured format that included questions in each of the following domains: 1 clinical facilities; 2 laboratory capacity with a focus on syphilis/HIV diagnosis; 3 clinic personnel; 4 physical space with a focus on locations to disclose confidential results; 5 financial support. Results Public STI clinics had free syphilis testing/treatment and laboratory facilities to perform essential syphilis and HIV tests. However, despite serving a large number of STI patients, private STI clinics lacked nontreponemal syphilis testing, HIV testing, and had fewer connections to the public health infrastructure. Formally trained assistant physicians were 2.5 times as common as physicians at STI clinics. Only one of the 8 sites had onsite voluntary counseling and testing (VCT services available. Conclusion These STI case studies reveal the potential for expanding integrated syphilis/HIV services at public STI clinics in China. More health services research is needed to guide scale-up of syphilis/HIV testing in China.

  7. Brucella Infection in HIV Infected Patients

    Directory of Open Access Journals (Sweden)

    SeyedAhmad SeyedAlinaghi

    2011-12-01

    Full Text Available The purpose of this study was to assess the possible correlation between Brucella and HIV infections. Iran is a country where HIV infection is expanding and Brucellosis is prevalent. In the present study, 184 HIV infected patients were assigned and for all of them HIV infection was confirmed by western blot test. In order to identify the prevalence rate of Brucella infection and systemic brucellosis in these subjects, sera samples were obtained and Brucella specific serological tests were performed to reveal antibody titers. Detailed history was taken and physical examination was carried out for all of patients. 11 (6% subjects had high titers but only 3 of them were symptomatic. Most of these subjects were injection drug user (IDU men and one was a rural woman. Considering both prevalence rates of Brucella infection (3% and symptomatic brucellosis (0.1% in Iran, our HIV positive patients show higher rates of Brucella infection and systemic brucellosis. Preserved cellular immunity of participants and retention of granulocytes activity may explain this poor association; whereas other explanations such as immunological state difference and non-overlapping geographical distribution of the 2 pathogens have been mentioned by various authors.

  8. The economics of HIV vaccines - Projecting the impact of HIV vaccination of infants in sub-Saharan Africa

    NARCIS (Netherlands)

    Bos, JM; Postma, MJ

    2001-01-01

    Objectives: (i) To project vaccine parameters, economic consequences and market size associated with HIV-1 vaccination of infants in sub-Saharan Africa through the Expanded Program on Immunisation (EPI); and (ii) to assess threshold values for price and effectiveness. Study design and methods:

  9. Delivering safer conception services to HIV serodiscordant couples in Kenya: perspectives from healthcare providers and HIV serodiscordant couples

    Directory of Open Access Journals (Sweden)

    Kenneth Ngure

    2017-02-01

    Conclusions: Antiretroviral-based HIV prevention is acceptable and accessible to meet the growing demand for safer conception services in Kenya, since medically assisted interventions are currently cost prohibitive. Cross-disciplinary training for health providers would expand confidence in all prevention options and foster the tailoring of counselling to couples’ preferences.

  10. FDA-Approved HIV Medicines

    Science.gov (United States)

    ... Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets FDA-Approved HIV Medicines Search Search ... This Fact Sheet Entire Series Related Content AIDSource | Treatment: Medication FDA Approval of ... | HIV/AIDS Medicines Drugs That Fight HIV-1 HIV and ...

  11. Expanding Scope of Practice for Ontario Optometrists

    National Research Council Canada - National Science Library

    Emily Bray; Ivy Bourgault

    2017-01-01

    In 2011, The Optometry Act, 1991 was amended to include The Designated Drugs and Standards of Practice Regulation which expanded the scope of practice for Ontario optometrists to include prescribing...

  12. Efficacy of Nickel-Titanium Palatal Expanders

    Directory of Open Access Journals (Sweden)

    Rahul Paul

    2011-01-01

    Conclusion : To conclude, a Ni-Ti expander brings about expansion by a combination of orthodontic and orthopedic effects by an increase in maxillary intermolar, maxillary intercanine and mandibular intercanine widths as also the opening of the midpalatal suture.

  13. From HIV prevention to reproductive health choices: HIV/AIDS treatment guidelines for women of reproductive age.

    Science.gov (United States)

    Stevens, Marion

    2008-11-01

    In South Africa, the private sector has responded to the HIV epidemic by providing treatment in the form of highly active antiretroviral therapy (HAART). The private sector has paved the way for policy and treatment regimens, while the public sector has reviewed health-systems capacity and the political will to provide treatment. The paradigm of prevention of mother-to-child transmission of HIV (PMTCT) has led the way as a clear evidenced-based method of treatment and prevention in South Africa. In sub-Saharan Africa, the HIV epidemic is feminised as a growing proportion of infections occurs among women or affects women. While access to HIV treatment has been contested in South Africa, women's sexual and reproductive health has been neglected. This paper is a reflection and critical review of current practice. Many HIV-positive women desire to choose to have a child, while the best choice of contraception for women on HAART is not well understood. In some areas there are reports of women being forced to accept injectable contraceptives. Some women who learn of their HIV-positive status during pregnancy may want to choose to terminate their pregnancy. There is a clear absence of HIV/AIDS-treatment guidelines for women of reproductive age, including options for HAART and options regarding fertility intentions. A range of other sexual and reproductive health areas (relevant to both the public and private health sectors) are neglected; these include depression and anxiety, violence against women, HIV-testing practices, screening for cervical cancer, and vaccination. Given the narrow focus of HAART, it is important to expand HIV treatment conceptually, by applying a broader view of the needs of working women (and men), and so contribute to better HIV prevention and treatment practices. There is a need to move from an HIV/AIDS-care maternal-health paradigm to one that embraces women's sexual and reproductive health and rights.

  14. European recommendations for the clinical use of HIV drug resistance testing: 2011 update.

    Science.gov (United States)

    Vandamme, Anne-Mieke; Camacho, Ricardo J; Ceccherini-Silberstein, Francesca; de Luca, Andreu; Palmisano, Lucia; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Schmit, Jean-Claude; Soriano, Vincent; Walter, Hauke; Sönnerborg, Anders

    2011-01-01

    The European HIV Drug Resistance Guidelines Panel, established to make recommendations to clinicians and virologists, felt that sufficient new information has become available to warrant an update of its recommendations, explained in both pocket guidelines and this full paper. The Panel makes the following recommendations concerning the indications for resistance testing: for HIV-1 (i) test earliest sample for protease and reverse transcriptase drug resistance in drug-naive patients with acute or chronic infection; (ii) test protease and reverse transcriptase drug resistance at virologic failure, and other drug targets (integrase and envelope) if such drugs were part of the failing regimen; (iii) consider testing for CCR5 tropism at virologic failure or when a change of therapy has to be made in absence of detectable viral load, and in the latter case test DNA or last detectable plasma RNA; (iv) consider testing earliest detectable plasma RNA when a successful nonnucleoside reverse transcriptase inhibitor-containing therapy was inappropriately interrupted; (v) genotype source patient when postexposure prophylaxis is considered; for HIV-2, (vi) consider resistance testing where treatment change is needed after treatment failure. The Panel recommends genotyping in most situations, using updated and clinically evaluated interpretation systems. It is mandatory that laboratories performing HIV resistance tests take part regularly in external quality assurance programs, and that they consider storing samples in situations where resistance testing cannot be performed as recommended. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response.

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

    Science.gov (United States)

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

    1997-01-01

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

  16. 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...

  17. Predictors of disease progression in HIV infection: a review

    Directory of Open Access Journals (Sweden)

    Ananworanich Jintanat

    2007-05-01

    Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

  18. HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs.

    Directory of Open Access Journals (Sweden)

    David Wilson

    2015-06-01

    Full Text Available There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection "Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers" highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.

  19. Assessment of HIV molecular surveillance capacity in the European Union, 2016.

    Science.gov (United States)

    Keating, Patrick; Pharris, Anastasia; Leitmeyer, Katrin; De Angelis, Stefania; Wensing, Annemarie; Amato-Gauci, Andrew J; Broberg, Eeva

    2017-12-01

    IntroductionExpanding access to HIV antiretroviral treatment is expected to decrease HIV incidence and acquired immunodeficiency syndrome (AIDS) mortality. However, this may also result in increased HIV drug resistance (DR). Better monitoring and surveillance of HIV DR is required to inform treatment regimens and maintain the long term effectiveness of antiretroviral drugs. As there is currently no formal European Union (EU)-wide collection of HIV DR data, this study aimed to assess the current HIV molecular surveillance capacity in EU/European Economic Area (EEA) countries in order to inform the planning of HIV DR monitoring at EU level. Methods: Thirty EU/EEA countries were invited to participate in a survey on HIV molecular surveillance capacity, which also included laboratory aspects. Results: Among 21 responding countries, 13 reported using HIV sequence data (subtype and/or DR) for surveillance purposes at national level. Of those, nine stated that clinical, epidemiological and sequence data were routinely linked for analysis. Discussion/conclusion: We identified similarities between existing HIV molecular surveillance systems, but also found important challenges including human resources, data ownership and legal issues that would need to be addressed.Information on capacities should allow better planning of the phased introduction of HIV DR surveillance at EU/EEA level.

  20. Remaining Gap in HIV Testing Uptake Among Female Sex Workers in Iran.

    Science.gov (United States)

    Shokoohi, Mostafa; Noori, Atefeh; Karamouzian, Mohammad; Sharifi, Hamid; Khajehkazemi, Razieh; Fahimfar, Noushin; Hosseini-Hooshyar, Samira; Kazerooni, Parvin Afsar; Mirzazadeh, Ali

    2017-08-01

    We estimated the prevalence of recent HIV testing (i.e., having an HIV test during the last 12 months and knew the results) among 1295 HIV-negative Iranian female sex workers (FSW) in 2015. Overall, 70.4% (95% confidence intervals: 59.6, 79.3) of the participants reported a recent HIV testing. Concerns about their HIV status (83.2%) was reported as the most common reason for HIV testing. Incarceration history, having >5 paying partners, having >1 non-paying partner, receiving harm reduction services, utilizing healthcare services, and knowing an HIV testing site were significantly associated with recent HIV testing. In contrast, outreach participants, having one non-paying sexual partner, and self-reported inconsistent condom use reduced the likelihood of recent HIV testing. HIV testing uptake showed a ~2.5 times increase among FSW since 2010. While these findings are promising and show improvement over a short period, HIV testing programs should be expanded particularly through mobile and outreach efforts.

  1. HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs.

    Science.gov (United States)

    Wilson, David

    2015-06-01

    There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection "Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers" highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.

  2. Rapid HIV testing for individuals on probation/parole: outcomes of an intervention trial.

    Science.gov (United States)

    Gordon, Michael S; Kinlock, Timothy W; McKenzie, Michelle; Wilson, Monique E; Rich, Josiah D

    2013-07-01

    Many probationers and parolees do not receive HIV testing despite being at increased risk for obtaining and transmitting HIV. A two-group randomized controlled trial was conducted between April, 2011 and May, 2012 at probation/parole offices in Baltimore, Maryland and Providence/Pawtucket, Rhode Island. Male and female probationers/parolees were interviewed (n = 1,263) and then offered HIV testing based on random assignment to one of two conditions: (1) On-site rapid HIV testing conducted at the probation/parole office; or (2) Referral for rapid HIV testing off site at a community HIV testing clinic. Outcomes were: (1) undergoing HIV testing; and (2) receipt of HIV testing results. Participants were significantly more likely to be tested on-site at a probation/parole office versus off-site at a HIV testing clinic (p < 0.001). There was no difference between the two groups in terms of receiving HIV testing results. Findings indicate that probationers/parolees are willing to be tested on-site and, independent of testing location, are equally willing to receive their results. Implications for expanding rapid HIV testing to more criminal justice related locations and populations are discussed.

  3. Experimental study on histopathological changes and tissue tropism of Iranian infectious bronchitis serotype 793/B-like virus in SPF chickens

    Directory of Open Access Journals (Sweden)

    Peyman Bijanzad

    2013-02-01

    Full Text Available Avian infectious bronchitis virus (IBV is prevalent in all countries with intensive poultry flocks. This disease is characterised primarily by respiratory signs, but some IBV strains may also infect other organs such as the intestinal and urogenital tracts. The aim of this study was to characterise the histopathological lesions and tissue tropism of Iranian isolate IR/773/2001(793/B of avian infectious bronchitis virus in different organs of experimentally infected SPF chickens. Forty-two one-day-old, specific pathogen-free (SPF chicks were divided randomly into two groups (21 chicks to each group. At the age of 12 days, one group was inoculated intra-ocularly with 103 EID50 of the 793/B isolate, and the other was kept as the control group. Tissue samples were collected at 2, 4, 6, 8, 10 and 12 days post-inoculation (PI. The IBV virus was detected in the caecal tonsils and cloaca from the 2nd to the 12th day PI. The virus was also detected in the kidneys from days 4–10 PI and in the bursa of Fabricius from days 4–12 PI. The virus was detected in the trachea, lungs and thymus. The most obvious histopathological lesions were found in the trachea, kidney, lungs and bursa of Fabricius. Amongst the lymphoid tissues, histopathological changes were found most frequently in the bursa of Fabricius. The results of this study indicated that the 793/B serotype of IBV is unlikely to cause mortality, severe clinical signs or gross lesions in infected chickens, but its replication in some tissues including the bursa of Fabricius could render birds susceptible to other micro-organisms.

  4. Novel IgG-Degrading Enzymes of the IgdE Protease Family Link Substrate Specificity to Host Tropism of Streptococcus Species.

    Science.gov (United States)

    Spoerry, Christian; Hessle, Pontus; Lewis, Melanie J; Paton, Lois; Woof, Jenny M; von Pawel-Rammingen, Ulrich

    2016-01-01

    Recently we have discovered an IgG degrading enzyme of the endemic pig pathogen S. suis designated IgdE that is highly specific for porcine IgG. This protease is the founding member of a novel cysteine protease family assigned C113 in the MEROPS peptidase database. Bioinformatical analyses revealed putative members of the IgdE protease family in eight other Streptococcus species. The genes of the putative IgdE family proteases of S. agalactiae, S. porcinus, S. pseudoporcinus and S. equi subsp. zooepidemicus were cloned for production of recombinant protein into expression vectors. Recombinant proteins of all four IgdE family proteases were proteolytically active against IgG of the respective Streptococcus species hosts, but not against IgG from other tested species or other classes of immunoglobulins, thereby linking the substrate specificity to the known host tropism. The novel IgdE family proteases of S. agalactiae, S. pseudoporcinus and S. equi showed IgG subtype specificity, i.e. IgdE from S. agalactiae and S. pseudoporcinus cleaved human IgG1, while IgdE from S. equi was subtype specific for equine IgG7. Porcine IgG subtype specificities of the IgdE family proteases of S. porcinus and S. pseudoporcinus remain to be determined. Cleavage of porcine IgG by IgdE of S. pseudoporcinus is suggested to be an evolutionary remaining activity reflecting ancestry of the human pathogen to the porcine pathogen S. porcinus. The IgG subtype specificity of bacterial proteases indicates the special importance of these IgG subtypes in counteracting infection or colonization and opportunistic streptococci neutralize such antibodies through expression of IgdE family proteases as putative immune evasion factors. We suggest that IgdE family proteases might be valid vaccine targets against streptococci of both human and veterinary medical concerns and could also be of therapeutic as well as biotechnological use.

  5. Rapid Selection in Modified BHK-21 Cells of a Foot-and-Mouth Disease Virus Variant Showing Alterations in Cell Tropism

    Science.gov (United States)

    Escarmís, Cristina; Carrillo, Elisa C.; Ferrer, Marcela; Arriaza, Juan F. García; Lopez, Nora; Tami, Cecilia; Verdaguer, Nuria; Domingo, Esteban; Franze-Fernández, Maria T.

    1998-01-01

    With persistent foot-and-mouth disease virus (FMDV) in BHK-21 cells, there is coevolution of the cells and the resident virus; the virulence of the virus for the parental BHK-21 cells is gradually increased, and the cells become partially resistant to FMDV. Here we report that variants of FMDV C3Arg/85 were selected in a single infection of partially resistant BHK-21 cells (termed BHK-Rb cells). Indirect immunofluorescence showed that the BHK-Rb cell population was heterogeneous with regard to susceptibility to C3Arg/85 infection. Infection of BHK-Rb cells with C3Arg/85 resulted in an early phase of partial cytopathology which was followed at 6 to 10 days postinfection by the shedding of mutant FMDVs, termed C3-Rb. The selected C3-Rb variants showed increased virulence for BHK-21 cells, were able to overcome the resistance of modified BHK-21 cells to infection, and had acquired the ability to bind heparin and to infect wild-type Chinese hamster ovary (CHO) cells. A comparison of the genomic sequences of the parental and modified viruses revealed only two amino acid differences, located at the surface of the particle, at the fivefold axis of the viral capsid (Asp-9→Ala in VP3 and either Gly-110→Arg or His-108→Arg in VP1). The same phenotypic and genotypic modifications occurred in a highly reproducible manner; they were seen in a number of independent infections of BHK-Rb cells with viral preparation C3Arg/85 or with clones derived from it. Neither amino acid substitutions in other structural or nonstructural proteins nor nucleotide substitutions in regulatory regions were found. These results prove that infection of partially permissive cells can promote the rapid selection of virus variants that show alterations in cell tropism and are highly virulent for the same cells. PMID:9811758

  6. Mechanisms of HIV persistence in HIV reservoirs.

    Science.gov (United States)

    Mzingwane, Mayibongwe L; Tiemessen, Caroline T

    2017-03-01

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

  7. Breaking Down the Siloes: Developing Effective Multidisciplinary HIV Research Teams.

    Science.gov (United States)

    Magnus, Manya; Castel, Amanda

    2016-09-01

    As the HIV epidemic passes its 35 years mark, the role of multidisciplinary approaches to HIV research has become increasingly important. Development of diverse, cross-cutting research teams has been found to be key to engaging and retaining participants in population-based studies; it is also a crucial component of designing studies capable of examining the sensitive and nuanced issues that surround HIV related risk and adherence behavior. Expanding our understanding of these issues is central to being able to overcome them and ultimately to the development of best practices for translation of research discovery into improvements in prevention and care. The objectives of this paper are to characterize the importance of multidisciplinary teams in HIV research where they are critical to gaining information that can have a positive impact on the epidemic and to propose specific methods for creating teams to conduct research with optimal public health impact.

  8. PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: review of clinical presentation in relation to immune responses.

    Directory of Open Access Journals (Sweden)

    Eduard E Zijlstra

    Full Text Available Co-infection of leishmaniasis and HIV is increasingly reported. The clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by HIV-induced immunosuppression. As leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (PKDL and cutaneous leishmaniasis (CL; dermal lesions are also commonly reported in visceral leishmaniasis (VL and HIV co-infection.We reviewed the literature with regard to dermal manifestations in leishmaniasis and HIV co-infection, in three clinical syndromes, according to the primary presentation: PKDL, VL, or CL.A wide variety of descriptions of dermal leishmaniasis in HIV co-infection has been reported. Lesions are commonly described as florid, symmetrical, non-ulcerating, nodular lesions with atypical distribution and numerous parasites. Pre-existing, unrelated dermal lesions may become parasitized. Parasites lose their tropism and no longer exclusively cause VL or CL. PKDL in HIV co-infected patients is more common and more severe and is not restricted to Leishmania donovani. In VL, dermal lesions occur in up to 18% of patients and may present as (severe localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis (DL or diffuse cutaneous leishmaniasis (DCL; there may be an overlap with para-kala-azar dermal leishmaniasis. In CL, dissemination in the skin may occur resembling DL or DCL; subsequent spread to the viscera may follow. Mucosal lesions are commonly found in VL or CL and HIV co-infection. Classical mucocutaneous leishmaniasis is more severe. Immune reconstitution disease (IRD is uncommon in HIV co-infected patients with leishmaniasis on antiretroviral treatment (ART.With increasing immunosuppression, the clinical syndromes of CL, VL, and PKDL become more severe and may overlap. These syndromes may be best described

  9. PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: review of clinical presentation in relation to immune responses.

    Science.gov (United States)

    Zijlstra, Eduard E

    2014-01-01

    Co-infection of leishmaniasis and HIV is increasingly reported. The clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by HIV-induced immunosuppression. As leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL); dermal lesions are also commonly reported in visceral leishmaniasis (VL) and HIV co-infection. We reviewed the literature with regard to dermal manifestations in leishmaniasis and HIV co-infection, in three clinical syndromes, according to the primary presentation: PKDL, VL, or CL. A wide variety of descriptions of dermal leishmaniasis in HIV co-infection has been reported. Lesions are commonly described as florid, symmetrical, non-ulcerating, nodular lesions with atypical distribution and numerous parasites. Pre-existing, unrelated dermal lesions may become parasitized. Parasites lose their tropism and no longer exclusively cause VL or CL. PKDL in HIV co-infected patients is more common and more severe and is not restricted to Leishmania donovani. In VL, dermal lesions occur in up to 18% of patients and may present as (severe) localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis (DL) or diffuse cutaneous leishmaniasis (DCL); there may be an overlap with para-kala-azar dermal leishmaniasis. In CL, dissemination in the skin may occur resembling DL or DCL; subsequent spread to the viscera may follow. Mucosal lesions are commonly found in VL or CL and HIV co-infection. Classical mucocutaneous leishmaniasis is more severe. Immune reconstitution disease (IRD) is uncommon in HIV co-infected patients with leishmaniasis on antiretroviral treatment (ART). With increasing immunosuppression, the clinical syndromes of CL, VL, and PKDL become more severe and may overlap. These syndromes may be best described as VL

  10. Integration of routine rapid HIV screening in an urban family planning clinic.

    Science.gov (United States)

    Criniti, Shannon M; Aaron, Erika; Hilley, Amy; Wolf, Sandra

    2011-01-01

    Family planning centers can play an important role in HIV screening, education, and risk-reduction counseling for women who are sexually active. This article describes how 1 urban Title X-funded family planning clinic transitioned from using a designated HIV counselor for targeted testing to a model that uses clinic staff to provide integrated, routine, nontargeted, rapid HIV testing as standard of care. Representative clinic staff members developed an integrated testing model that would work within the existing clinic flow. Education sessions were provided to all staff, signs promoting routine HIV testing were posted, and patient and clinician information materials were developed. A review of HIV testing documentation in medical charts was performed after the new model of routine, nontargeted, rapid HIV testing was integrated, to determine any changes in patient testing rates. A survey was given to all staff members 6 months after the transition to full integration of HIV testing to evaluate the systems change process. Two years after the transition, the rate of patients with an HIV test in the medical chart within the last 12 months increased 25.5%. The testing acceptance rate increased 17%. Sixteen HIV seropositive individuals were identified and linked into medical care. All surveyed clinic staff agreed that offering routine HIV screening to all patients is very important, and 78% rated the integration efforts as successful. Integrating routine HIV screening into a family planning clinic can be critical to identifying new HIV infections in women. This initiative demonstrated that routine, nontargeted, rapid HIV screening can be offered successfully as a standard of care in a high-volume, urban, reproductive health care setting. This description and evaluation of the process of changing the model of HIV testing in a clinic setting is useful for clinicians who are interested in expanding routine HIV testing in their clinics. © 2011 by the American College of

  11. 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

  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. 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: July 26, 2017 ...

  14. 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 ...

  15. Travelers' Health: HIV Infection

    Science.gov (United States)

    ... Share Compartir Chapter 3 - Histoplasmosis Chapter 3 - Influenza HIV Infection Philip J. Peters, John T. Brooks INFECTIOUS AGENT ... skin (see Chapter 8, Health Care Workers ). EPIDEMIOLOGY HIV infection occurs worldwide. As of the end of 2014, ...

  16. HIV Resistance Testing

    Science.gov (United States)

    ... 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE DEVELOP? ... one or more ARVs. This is called transmitted resistance. The more that HIV multiplies, the more mutations ...

  17. Mouth Problems and HIV

    Science.gov (United States)

    ... AIDS > Mouth Problems and HIV Mouth Problems and HIV Main Content This information is for people who ... fever blisters. Sometimes Yes Prescription pill can reduce healing time and frequency of outbreaks. Click to enlarge ...

  18. Experiences of and responses to HIV among African and Caribbean communities in Toronto, Canada.

    Science.gov (United States)

    Gardezi, F; Calzavara, L; Husbands, W; Tharao, W; Lawson, E; Myers, T; Pancham, A; George, C; Remis, R; Willms, D; McGee, F; Adebajo, S

    2008-07-01

    African and Caribbean communities in Canada and other developed countries are disproportionately affected by HIV/AIDS. This qualitative study of African and Caribbean communities in Toronto sought to understand HIV-related stigma, discrimination, denial and fear, and the effects of multiple intersecting factors that influence responses to the disease, prevention practices and access to treatment and support services. Semi-structured interviews were conducted with 30 HIV-positive men and women and focus groups were conducted with 74 men and women whose HIV status was negative or unknown. We identified a range of issues faced by African and Caribbean people that may increase the risk for HIV infection, create obstacles to testing and treatment and lead to isolation of HIV-positive people. Our findings suggest the need for greater sensitivity and knowledge on the part of healthcare providers; more culturally specific support services; community development; greater community awareness; and expanded efforts to tackle housing, poverty, racism and settlement issues.

  19. Influence of HIV and HCV on T cell antigen presentation and challenges in the development of vaccines.

    Science.gov (United States)

    John, Mina; Gaudieri, Silvana

    2014-01-01

    Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4(+) and CD8(+) T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of "elite controllers," or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8(+) T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human

  20. Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

    Science.gov (United States)

    Hauser, Kurt F; Knapp, Pamela E

    2014-01-01

    Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

  1. HIV protease inhibitor resistance

    NARCIS (Netherlands)

    Wensing, Annemarie M.J.; Fun, Axel; Nijhuis, Monique

    2017-01-01

    HIV protease is pivotal in the viral replication cycle and directs the formation of mature infectious virus particles. The development of highly specific HIV protease inhibitors (PIs), based on thorough understanding of the structure of HIV protease and its substrate, serves as a prime example of

  2. Primaer HIV-infektion

    DEFF Research Database (Denmark)

    Pedersen, C; Pedersen, B K

    1996-01-01

    , oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove...

  3. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    Jun 15, 2007 ... necessary tests are done initially and the correct treatment started. ... thrombocytopenia is prone to a more rapid acceleration of disease. ... Platelet life span is decreased in HIV-induced idiopathic thrompocytopenic purpura (ITP) and in. HIV patients without ITP. It seems as if HIV stimulates CD5+ cells.

  4. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: A combined analysis of 12 mathematical models

    NARCIS (Netherlands)

    J.W. Eaton (Jeffrey); D. Menzies; J. Stover (John); V. Cambiano (Valentina); L. Chindelevitch (Leonid); A. Cori (Anne); J.A.C. Hontelez (Jan); S. Humair (Salal); C.C. Kerr (Cliff); D.J. Klein (David); S. Mishra (Sharmistha); K.M. Mitchell (Kate); B.E. Nichols (Brooke); K. Vickerman; R. Bakker (Roel); T. Bärnighausen (Till); A. Bershteyn (Anna); D.E. Bloom (David); M-C. Boily (Marie-Claude); S.T. Chang (Stewart); T. Cohen (Ted); P. Dodd (Peter); C. Fraser (Christophe); C. Gopalappa (Chaitra); J. Lundgren (Jens); N.K. Martin (Natasha); T.S. Mikkelsen; E. Mountain (Elisa); Q.D. Pham (Quang); T. Pickles (Tom); A. Phillips (Andrew); S. Platt; C. Pretorius (Carel); H.J. Prudden (Holly); J.A. Salomon (Joshua); D.A.M.C. van de Vijver (David); S.J. de Vlas (Sake); B.G. Wagner (Bradley); R.G. White (Richard); D.C. Wilson (David); L. Zhang (Lingling); J. Blandford (John); G. Meyer-Rath (Gesine); M. Remme (Michelle); P. Revill (Paul); N. Sangrujee (Nalinee); F. Terris-Prestholt (Fern); M.C. Doherty (Meg); N. Shaffer (Nathan); P.J. Easterbrook (Philippa); G. Hirnschall (Gottfried); T.B. Hallett (Timothy)

    2014-01-01

    textabstractBackground: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for

  5. A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets.

    Directory of Open Access Journals (Sweden)

    Neeltje van Doremalen

    Full Text Available The first pandemic of the 21(st century, pandemic H1N1 2009 (pH1N1 2009, emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.

  6. Design of laser afocal zoom expander system

    Science.gov (United States)

    Jiang, Lian; Zeng, Chun-Mei; Hu, Tian-Tian

    2018-01-01

    Laser afocal zoom expander system due to the beam diameter variable, can be used in the light sheet illumination microscope to observe the samples of different sizes. Based on the principle of afocal zoom system, the laser collimation and beam expander system with a total length of less than 110mm, 6 pieces of spherical lens and a beam expander ratio of 10 is designed by using Zemax software. The system is focused on laser with a wavelength of 532nm, divergence angle of less than 4mrad and incident diameter of 4mm. With the combination of 6 spherical lens, the beam divergence angle is 0.4mrad at the maximum magnification ratio, and the RMS values at different rates are less than λ/4. This design is simple in structure and easy to process and adjust. It has certain practical value.

  7. Bank Directors’ Perceptions of Expanded Auditor's Reports

    DEFF Research Database (Denmark)

    Boolaky, Pran Krishansing; Quick, Reiner

    2016-01-01

    of expanded audit reports, namely information on the assurance level, materiality levels and key audit matters (KAM), on bank director perceptions of the quality of the financial statements, the audit and the audit report, as well as on their credit approval decisions. We conduct an experiment involving......Subsequent to the financial crisis, standard setters developed suggestions for enhancing the audit function, in order to increase financial stability. One related idea is to expand the audit report disclosed to the public, to ensure that it is fit for purpose. This study investigates the impact...... the materiality level or KAM. As a consequence, standard setters should carefully analyse the effect of additional information before making decisions on expanding the content of the audit report. Such expansions are not necessarily perceived as useful by stakeholders. © 2016 John Wiley & Sons Ltd...

  8. HIV antibodies for treatment of HIV infection

    Science.gov (United States)

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

    2016-01-01

    Summary 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. Further, 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. PMID:28133794

  9. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith

    2013-01-01

    The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include...... inexpensive synthesis, constant availability, a good safety profile, biodegradability and the long clinical use as plasma expanders. Three polymers have been tested for cytotoxicity and cytokine activation in cell cultures and conjugated with a near-infrared fluorescent dye: hydroxyethyl starches (HES 200 k...

  10. Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection.

    Science.gov (United States)

    Hirsch, Christina S; Baseke, Joy; Kafuluma, John Lusiba; Nserko, Mary; Mayanja-Kizza, Harriet; Toossi, Zahra

    2016-01-01

    CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3+ CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3+ CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known. Pleural fluid mononuclear cells (PFMC) from HIV/TB co-infected patients with pleural TB were characterized by immune-staining and FACS analysis for surface markers CD4, CD127, CCR5, CXCR4, HLA-DR and intracellular expression of Foxp3, HIVp24, IFN-γ and Bcl-2. Whole PFMC and bead separated CD4+CD25+CD127- T cells were assessed for HIV-1 LTR strong stop (SS) DNA by real-time PCR, which represents viral DNA post cell entry and initiation of reverse transcription. High numbers of HIV-1 p24 positive Foxp3+ and Foxp3+CD127- CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4+Foxp3+CD127- T cells displayed high expression of the cellular activation marker, HLA-DR. Further, expression of the HIV-1 co-receptors, CCR5 and CXCR4, were higher on CD4+Foxp3+T cells compared to CD4+Foxp3- T cells. Purified CD4+CD25+CD127- T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4+Foxp3+T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4+CD25+CD127- T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24+ Foxp3+ CD4+T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24+ Foxp3- CD4 T cells, and Foxp3+ CD4+T cells without HIV-p24 expression. Foxp3+ CD4 T cells in PFMC from HIV/TB co-infected subjects are predisposed to productive HIV-1 infection and have survival advantage as compared to Foxp3 negative CD4 T cells.

  11. Epigenetic heterogeneity in HIV-1 latency establishment.

    Science.gov (United States)

    Matsuda, Yuka; Kobayashi-Ishihara, Mie; Fujikawa, Dai; Ishida, Takaomi; Watanabe, Toshiki; Yamagishi, Makoto

    2015-01-09

    Despite prolonged antiretroviral therapy, HIV-1 persists as transcriptionally inactive proviruses. The HIV-1 latency remains a principal obstacle in curing AIDS. It is important to understand mechanisms by which HIV-1 latency is established to make the latent reservoir smaller. We present a molecular characterization of distinct populations at an early phase of infection. We developed an original dual-color reporter virus to monitor LTR kinetics from establishment to maintenance stage. We found that there are two ways of latency establishment i.e., by immediate silencing and slow inactivation from active infection. Histone covalent modifications, particularly polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation, appeared to dominate viral transcription at the early phase. PRC2 also contributes to time-dependent LTR dormancy in the chronic phase of the infection. Significant differences in sensitivity against several stimuli were observed between these two distinct populations. These results will expand our understanding of heterogeneous establishment of HIV-1 latency populations.

  12. Opt-out of voluntary HIV testing: a Singapore hospital's experience.

    Directory of Open Access Journals (Sweden)

    Arlene C Chua

    Full Text Available INTRODUCTION: Since 2008, the Singapore Ministry of Health (MOH has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH, the second largest acute care general hospital in Singapore. METHODS AND FINDINGS: From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675 opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63% were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4-1.6, aged >60 years (OR: 2.3, 95%CI: 2.2-2.4 and Chinese ethnicity (OR: 1.7, 95%CI:1.6-1.8. The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All 16 confirmed HIV patients were linked to care. CONCLUSION: The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.

  13. Nine Crystal Structures Determine the Substrate Envelope of the MDR HIV-1 Protease

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhigang; Wang, Yong; Brunzelle, Joseph; Kovari, Iulia A.; Kovari, Ladislau C. (WSU-MED); (NWU)

    2012-03-27

    Under drug selection pressure, emerging mutations render HIV-1 protease drug resistant, leading to the therapy failure in anti-HIV treatment. It is known that nine substrate cleavage site peptides bind to wild type (WT) HIV-1 protease in a conserved pattern. However, how the multidrug-resistant (MDR) HIV-1 protease binds to the substrate cleavage site peptides is yet to be determined. MDR769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) was selected for present study to understand the binding to its natural substrates. MDR769 HIV-1 protease was co-crystallized with nine substrate cleavage site hepta-peptides. Crystallographic studies show that MDR769 HIV-1 protease has an expanded substrate envelope with wide open flaps. Furthermore, ligand binding energy calculations indicate weaker binding in MDR769 HIV-1 protease-substrate complexes. These results help in designing the next generation of HIV-1 protease inhibitors by targeting the MDR HIV-1 protease.

  14. Diet and Nutrition and HIV

    Science.gov (United States)

    ... with HIV/AIDS: Diet and Nutrition--Entire Lesson HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... code here Enter ZIP code here Living with HIV/AIDS: Diet and Nutrition--Entire Lesson for Veterans ...

  15. Serological markers in HIV infection

    NARCIS (Netherlands)

    Lange, J. M.; Goudsmit, J.; de Wolf, F.; Coutinho, R. A.; van der Noordaa, J.

    1988-01-01

    HIV antigenaemia can be detected at or possibly before the onset of clinical symptoms of primary HIV infection. Approximately one week after the onset of HIV antigenaemia, a primary anti-HIV IgM response may occur. A week later, generally within 3 to 6 weeks after infection, anti-HIV IgG can be

  16. Tropisme géographique et tropisme photographique.

    Directory of Open Access Journals (Sweden)

    Pierre-Arnaud Chouvy

    2008-06-01

    Full Text Available Si le géographe est souvent aussi photographe, le photographe, lui, est plus rarement géographe. Tout le monde est certes un peu géographe, ainsi que les géographes Michel Sivignon et Jean-Paul Charvet l’ont suggéré, et le discours de nombreux photographes témoigne, si besoin était, sinon de leur disposition géographique, du moins de leur curiosité du monde, de l’impératif besoin de découverte, d’exploration, de connaissance, et de compréhension du monde qui les anime ...

  17. Molecular characterization, tissue tropism, and genetic variability of the novel Mupapillomavirus type HPV204 and phylogenetically related types HPV1 and HPV63.

    Directory of Open Access Journals (Sweden)

    Anja Šterbenc

    Full Text Available HPV204 is the only newly identified Mupapillomavirus (Mu-PV type in more than a decade. To comprehensively characterize HPV204, we performed a detailed molecular analysis of the viral genome and evaluated its clinical relevance in comparison to the other Mu-PVs, HPV1 and HPV63. The 7,227-bp long genome of HPV204 exhibits typical genomic organization of Mu-PVs with eight open reading frames (ORFs (E6, E7, E1, E2, E8, E4, L2, and L1. We developed three type-specific quantitative real-time PCRs and used them to test a representative collection (n = 1,006 of various HPV-associated benign and malignant neoplasms, as well as samples of clinically normal cutaneous, mucosal, and mucocutaneous origins. HPV204, HPV1, and HPV63 were detected in 1.1%, 2.7%, and 1.9% of samples tested, respectively, and were present in skin and mucosa, suggesting dual tissue tropism of all Mu-PVs. To evaluate the etiological role of Mu-PVs in the development of HPV-associated neoplasms, Mu-PV viral loads per single cell were estimated. HPV1 and HPV63 were present in high viral copy numbers in 3/43 and 1/43 cutaneous warts, respectively, and were identified as the most likely causative agents of these warts. HPV204 viral load was extremely low in a single HPV204-positive cutaneous wart (7.4 × 10-7 viral copies/cell. Hence, etiological association between HPV204 and the development of cutaneous warts could not be established. To the best of our knowledge, this is the first study to evaluate the genetic variability of Mu-PVs by sequencing complete LCR genomic regions of HPV204, HPV1, and HPV63. We detected several nucleotide substitutions and deletions within the LCR genomic regions of Mu-PVs and identified two genetic variants of HPV204 and HPV63 and five genetic variants of HPV1.

  18. Replicating an expanded genetic alphabet in cells.

    Science.gov (United States)

    Chaput, John C

    2014-09-05

    Recent advances in synthetic biology have made it possible to replicate an unnatural base pair in living cells. This study highlights the technologies developed to create a semisynthetic organism with an expanded genetic alphabet and the potential challenges of moving forward. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Expanding the Focus of Career Assessment.

    Science.gov (United States)

    Lock, Jared D.; Hogan, Robert

    2000-01-01

    Issues affecting career assessment include change in the focus and definition of career, emphasis on quality of work life, expansion of career paths, increased amount of career information available on the Internet, and questionable quality of online assessment. An expanded model of career assessment now includes technical fit, personal fit,…

  20. Expanding CTE Opportunities through Blended Learning

    Science.gov (United States)

    McKinstry, Elizabeth

    2012-01-01

    The global economy, 21st century skills, knowledge society, college and career readiness, digital and project-based learning are all common terms to educators who are expanding their learning environments beyond the classroom to meet the needs of all students. It is common knowledge that the rapid technological advances of this century have…

  1. Expanding the Reader Landscape of Histone Acylation.

    Science.gov (United States)

    Khan, Abid; Bridgers, Joseph B; Strahl, Brian D

    2017-04-04

    In this issue of Structure,Klein et al. (2017) expand our understanding of what reader domains bind to by showing that MORF, a double PHD domain containing lysine acetyltransferase, is a preferential reader of histone lysine acylation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Sulfonated graphenes catalyzed synthesis of expanded porphyrins ...

    Indian Academy of Sciences (India)

    A newer synthesis of sulfonic acid functionalized graphenes have been developed, which have been characterized, examined as heterogeneous solid acid carbocatalyst in the synthesis of selected expanded porphyrins in different reaction conditions. This environment-friendly catalyst avoids the use of toxic catalysts and ...

  3. Expanding Your Horizons Conference in Geneva

    CERN Multimedia

    Chromek-Burckhart, Doris

    2011-01-01

    CERN and its experiments participated in Expanding Your Horizons (EYH) in Science and Mathematics conference in Geneva on 12th November. EYH nurture girls' interest in science and math courses to encourage them to consider careers in science, technology, engineering, and math.

  4. Sulfonated graphenes catalyzed synthesis of expanded porphyrins ...

    Indian Academy of Sciences (India)

    Abstract. A newer synthesis of sulfonic acid functionalized graphenes have been developed, which have been characterized, examined as heterogeneous solid acid carbocatalyst in the synthesis of selected expanded porphyrins in different reaction conditions. This environment-friendly catalyst avoids the use of toxic ...

  5. Technical Note: Effect of Incorporating Expanded Polystyrene ...

    African Journals Online (AJOL)

    Incorporating expanded polystyrene granules in concrete matrix can produce lightweight polystyrene aggregate concrete of various densities. Workability which is an important property of concrete, aects the rate of placement and the degree of compaction of concrete. Inadequate compaction leads to reduction in both ...

  6. Hubble, Hubble's Law and the Expanding Universe

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 3. Hubble, Hubble's Law and the Expanding Universe. J S Bagla. General Article Volume 14 Issue 3 March 2009 pp 216-225. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/014/03/0216-0225 ...

  7. Expanding the collaboration between CERN and Pakistan

    CERN Multimedia

    2002-01-01

    Parvez Butt, chairman of the Pakistan Atomic Energy Commission, and CERN Director General, Luciano Maiani, signed a letter of intent last week to expand collaboration. Through an agreement which should be formalized within a few months, Pakistan would make a substantial contribution to the LHC and its detectors, coordinated by the Pakistani National Centre of Physics.

  8. Circle diffeomorphisms forced by expanding circle maps

    NARCIS (Netherlands)

    Homburg, A.J.

    2012-01-01

    We discuss the dynamics of skew product maps defined by circle diffeomorphisms forced by expanding circle maps. We construct an open class of such systems that are robustly topologically mixing and for which almost all points in the same fiber converge under iteration. This property follows from the

  9. Discrete Groups, Expanding Graphs and Invariant Measures

    CERN Document Server

    Lubotzky, Alexander

    2009-01-01

    Presents the solutions to two problems: the first is the construction of expanding graphs - graphs which are of fundamental importance for communication networks and computer science, and the second is the Ruziewicz problem concerning the finitely additive invariant measures on spheres

  10. Expanding Educational Excellence: The Power of Schools

    Science.gov (United States)

    Coleman, Mary Ruth; Winn, Donna-Marie; Harradine, Christine

    2012-01-01

    In this paper, the authors explore four major barriers to academic success that must be addressed, briefly describe two projects that have worked to address these barriers, and make recommendations for moving forward as they work to expand educational excellence for all students. They provide examples of the myriad ways in which schools have the…

  11. Expanded Core Curriculum: 12 Years Later

    Science.gov (United States)

    Lohmeier, Keri; Blankenship, Karen; Hatlen, Phil

    2009-01-01

    This study investigated changes in teachers' and parents' understanding and implementation of or philosophy on the implementation of the content areas of the expanded core curriculum for students who are visually impaired. The results demonstrated some changes since the original survey results were reported in 1998 and a discrepancy between the…

  12. CLASSICS WHY THE UNIVERSE IS EXPANDING

    Indian Academy of Sciences (India)

    (H. G. Wells, The Time Machine and other Stories). WHY IS THE UNIVERSE EXPANDING? Chemical Explosion and Astrophysical Explosion Similarities and Differences. The expansion of the Universe is a reliably established fact. There was the “Big Bang” about 15 billion years ago. But why did it happen? What are the ...

  13. Hubble, Hubble's Law and the Expanding Universe

    Indian Academy of Sciences (India)

    Srimath

    H ubble's nam e is associated closely w ith the idea of an expanding universe as he discovered the relation between the recession velocity and the distances of galaxies. H ubble also did a lot of pioneering w ork on the distribution of galaxies in the universe. In this article we take a look at H ubble's law and discuss how it ...

  14. Women Engineering Faculty: Expanding the Pipeline

    Science.gov (United States)

    Greni, Nadene Deiterman

    2006-01-01

    The purpose for this case study was to explore the features of undergraduate engineering departmental and college support that influenced the persistence of women students. Women engineering faculty members were among the participants at three Land Grant universities in the Midwest. The data revealed the theme, Expanding the Pipeline, and…

  15. Expanded austenite, crystallography and residual stress

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Hummelshøj, Thomas Strabo; Somers, Marcel A. J.

    2010-01-01

    compositions and (b) unravelling of the contributions of stress-depth and composition-depth profiles in expanded austenite layers are summarised and discussed. It is shown through simulation of line profiles that the combined effects of composition gradients, stress gradients and stacking fault gradients can...

  16. Seeking information about HIV/AIDS: a qualitative study of health literacy among people living with HIV/AIDS in a low prevalence context.

    Science.gov (United States)

    Zukoski, Ann P; Thorburn, Sheryl; Stroud, Josh

    2011-11-01

    People living with HIV/AIDS in rural and low HIV prevalence areas face a number of challenges including stigma, limited access to specialized medical care, lack of an HIV/AIDS specialist and fear which may interfere with their ability to find and use information to manage their health. With a large number of HIV cases located in non-metropolitan and rural areas in the US, more research is needed to better understand the health seeking behaviors of individuals living in this context. This study examined how 16 individuals living with HIV sought out information to meet their health needs. In qualitative semi-structured interviews, we explored participants' primary sources of information, types of information sought, and barriers to accessing information. The sample was comprised of people living with HIV/AIDS (PLWHA) who resided in a predominantly rural area with low HIV prevalence. The majority of participants relied on a combination of sources including their HIV/AIDS physician, the Internet, a Ryan-White caseworker and a staff member of a community-based support organization to meet their informational needs. Information sought focused primarily on drug regimens, drug side effects, or drug research. Participants shared barriers to accessing information including stigma, fear, concern about disclosure, and feelings of futility and anger. Findings point to a need to expand health literacy research and interventions to address broader social and structural barriers to health improvement for PLWHA, especially among those living in rural and low HIV prevalence areas.

  17. Refrigeration generation using expander-generator units

    Science.gov (United States)

    Klimenko, A. V.; Agababov, V. S.; Koryagin, A. V.; Baidakova, Yu. O.

    2016-05-01

    The problems of using the expander-generator unit (EGU) to generate refrigeration, along with electricity were considered. It is shown that, on the level of the temperatures of refrigeration flows using the EGU, one can provide the refrigeration supply of the different consumers: ventilation and air conditioning plants and industrial refrigerators and freezers. The analysis of influence of process parameters on the cooling power of the EGU, which depends on the parameters of the gas expansion process in the expander and temperatures of cooled environment, was carried out. The schematic diagram of refrigeration generation plant based on EGU is presented. The features and advantages of EGU to generate refrigeration compared with thermotransformer of steam compressive and absorption types were shown, namely: there is no need to use the energy generated by burning fuel to operate the EGU; beneficial use of the heat delivered to gas from the flow being cooled in equipment operating on gas; energy production along with refrigeration generation, which makes it possible to create, using EGU, the trigeneration plants without using the energy power equipment. It is shown that the level of the temperatures of refrigeration flows, which can be obtained by using the EGU on existing technological decompression stations of the transported gas, allows providing the refrigeration supply of various consumers. The information that the refrigeration capacity of an expander-generator unit not only depends on the parameters of the process of expansion of gas flowing in the expander (flow rate, temperatures and pressures at the inlet and outlet) but it is also determined by the temperature needed for a consumer and the initial temperature of the flow of the refrigeration-carrier being cooled. The conclusion was made that the expander-generator units can be used to create trigeneration plants both at major power plants and at small energy.

  18. Measuring the impact of HIV and STIs in a community in a coal mining town, Mpumalanga, South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Hurkchand, H.; Makuluma, H.; Molefe, N.; Molapo, M.

    2005-07-01

    A cross-sectional study was conducted in November 2001 to establish the prevalence rates of Human Immunodeficiency Virus (HIV) and sexually transmitted infections (STIs) (Chlamydia trachomatis and Neisseria gonorrhoea) in a coalmining town in Mpumalanga. HIV prevalence in this community is high, and corresponds to national figures. However, the prevalence of STIs is surprisingly low as it would be expected to be high in a migrant population. Although communities are exposed to expanding peer-education activities that encourage behaviour change, the prevalence of HIV in this group. There is an urgent need for interventions designed to treat or prevent HIV infection in women generally and in women at high risk.

  19. Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database: an expanded data model integrating natural language text and sequence analysis programs.

    Science.gov (United States)

    Kantor, R; Machekano, R; Gonzales, M J; Dupnik, K; Schapiro, J M; Shafer, R W

    2001-01-01

    The HIV Reverse Transcriptase and Protease Sequence Database is an on-line relational database that catalogs evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of anti-HIV therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions from International Collaboration databases and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the antiretroviral drug treatment history of the individual from whom the isolate was obtained. During the past year 3500 sequences have been added and the data model has been expanded to include drug susceptibility data on sequenced isolates. Database content has also been integrated with didactic text and the output of two sequence analysis programs.

  20. Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities

    DEFF Research Database (Denmark)

    Leitman, Ellen M.; Palmer, Christine D.; Buus, Søren

    2017-01-01

    Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We...... of these reagents is demonstrated here in identifying the CD8+ T-cell specificity most effective in preventing HIV progression in HIV-infected HLA-B*27-positive immune controllers....

  1. 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 ...

  2. 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 ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

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

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

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

  7. Drugs + HIV, Learn the Link

    Medline Plus

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

  8. 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 ...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Misuse and HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the beginning ... the link between drug misuse and HIV. We have produced a set of multicultural public service announcements ( ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... by HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This site provides information both for ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... between drug abuse and HIV/AIDS. In the early years of the HIV epidemic, it became clear ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  12. Women and HIV/AIDS

    Science.gov (United States)

    ... AIDS from other websites National Women and Girls HIV/AIDS Awareness Day Blog topics HIV and AIDS Breaking Down ... t Miss a Beat National Women and Girls HIV/AIDS Awareness Day National Women's Health Week Supporting Nursing Moms ...

  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 ... brain. Research has shown that HIV causes greater injury to cells in the brain and cognitive impairment ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

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

  15. 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 ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

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

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... effects of drugs. Drug abuse 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 ...

  18. Parameter estimation for an expanding universe

    Directory of Open Access Journals (Sweden)

    Jieci Wang

    2015-03-01

    Full Text Available We study the parameter estimation for excitations of Dirac fields in the expanding Robertson–Walker universe. We employ quantum metrology techniques to demonstrate the possibility for high precision estimation for the volume rate of the expanding universe. We show that the optimal precision of the estimation depends sensitively on the dimensionless mass m˜ and dimensionless momentum k˜ of the Dirac particles. The optimal precision for the ratio estimation peaks at some finite dimensionless mass m˜ and momentum k˜. We find that the precision of the estimation can be improved by choosing the probe state as an eigenvector of the hamiltonian. This occurs because the largest quantum Fisher information is obtained by performing projective measurements implemented by the projectors onto the eigenvectors of specific probe states.

  19. Microwave Energy for Expanding Perlite Ore

    Directory of Open Access Journals (Sweden)

    J.A. Aguilar-Garib

    2013-12-01

    Full Text Available Perlite is an igneous mineral composed by silicon, aluminum, oxygen and water. It can be expanded by heating it up at temperatures above 870 °C, then it becomes plastic, and the steam formed inside pressures out of the mineral. Maximum expansion is possible if the particles are heated up quickly, since the expansion degree strongly depends on the remaining water in the particles at the time that they reach the temperature where they become plastic. The typical expansion process consist in pouring the particles in rotary kilns operated with natural gas, but it is proposed in this research that the particles can be heated quickly with microwaves at 2.45 GHz. Particles of 0.08 cm and 0.018 cm of average diameter were expanded 10 to 20 times.

  20. 9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity.

    Directory of Open Access Journals (Sweden)

    James J Kobie

    Full Text Available The induction of a broadly neutralizing antibody (BNAb response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE patients, both of which positively correlated with HIV viral load. Compared to the global 9G4-IgD--memory B cell population, the 9G4+IgD--memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward "IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019 with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in

  1. Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Mondal Debasis

    2011-01-01

    Full Text Available Abstract Background Tissue resident mesenchymal stem cells (MSCs are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD cells derived from ASCs could productively be infected with HIV-1. Results HD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-. Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. Conclusions Considering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

  2. Expanding roles for GILT in immunity

    OpenAIRE

    West, Laura Ciaccia; Cresswell, Peter

    2012-01-01

    Gamma-interferon-inducible lysosomal thiol reductase (GILT), a thioredoxin-related oxidoreductase, functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation. However, recent reports have greatly expanded our understanding of GILT’s function. Several studies of GILT and antigen processing have shown that the influence of GILT on the peptide re...

  3. Japan: Implications of an Expanded Military Role,

    Science.gov (United States)

    1985-07-03

    served by diplomatic, economic and foreign assistance strategies. The Fukuda and Ohira " doctrines " emphasized the role of non-military policy in...encourage it to expand economic assistance under the comprehensive security doctrine . Weinstein is criticizing U.S. policy toward the Soviet Union; he...the United States. The second category of opinion which developed centered -~ on support for a policy line orginally set forth In the Yoshida Doctrine

  4. 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.

  5. Travelling with HIV

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  6. Characterization of commercial expandable graphite fire retardants

    Energy Technology Data Exchange (ETDEWEB)

    Focke, Walter Wilhelm, E-mail: walter.focke@up.ac.za; Badenhorst, Heinrich; Mhike, Washington; Kruger, Hermanus Joachim; Lombaard, Dewan

    2014-05-01

    Highlights: • Expandable graphite is less well-ordered than its graphite bisulfate progenitor. • It includes graphite oxide as a randomly interstratified phase. • CO{sub 2}, CO and SO{sub 2} are released during thermal-driven exfoliation. - Abstract: Thermal analysis and other techniques were employed to characterize two expandable graphite samples. The expansion onset temperatures of the expandable graphite's were ca. 220 °C and 300 °C respectively. The key finding is that the commercial products are not just pure graphite intercalation compounds with sulfuric acid species intercalated as guest ions and molecules in between intact graphene layers. A more realistic model is proposed where graphite oxide-like layers are also randomly interstratified in the graphite flakes. These graphite oxide-like layers comprise highly oxidized graphene sheets which contain many different oxygen-containing functional groups. This model explains the high oxygen to sulfur atomic ratios found in both elemental analysis of the neat materials and in the gas generated during the main exfoliation event.

  7. Evolving paradigms in the pathogenesis of HIV-1-associated dementia.

    Science.gov (United States)

    Fischer-Smith, Tracy; Rappaport, Jay

    2005-12-02

    HIV-1-associated dementia (HIV-D) remains a significant consequence of HIV-1 infection and AIDS. Since the clinical introduction of highly active antiretroviral therapy (HAART), the incidence of HIV-D has decreased, yet the prevalence has increased as patients are living longer under treatment. Additionally, a less severe form of HIV-D, minor cognitive motor disorder, has become an increasing issue. Two different models have been proposed for virus entry in the central nervous system (CNS) in HIV-D. In the 'Trojan horse' model, the virus enters the CNS early carried by macrophages and infects resident glia; later in the course of infection, virus replication is activated and additional monocyte/macrophages are recruited into the CNS via cytokine/chemokine networks and endothelial-cell-leukocyte interactions at the blood-brain barrier. In the 'late invasion' model, an inherently invasive activated monocyte subset is expanded from bone marrow as a result of immune dysregulation in the periphery in the setting of AIDS. In this review we discuss these two separate, although not mutually exclusive, means for virus entry and persistence in the CNS. Additionally, we explore mechanisms for neuronal injury and apoptosis, including the role of virus, viral and host proteins, oxidative stress and products of infected or uninfected activated microglia and astrocytes. Potential therapeutic strategies are also briefly discussed.

  8. Characteristics of HIV seroprevalence of visitors to public health centers under the national HIV surveillance system in Korea: cross sectional study

    Directory of Open Access Journals (Sweden)

    Kim Sung-Soon

    2009-05-01

    expand the anonymous testing centers and Voluntary Counselling and Testing Program (VCT for general population to easily access to HIV testing.

  9. Exploring the social meaning of curing HIV: a qualitative study of people who inject drugs in Guangzhou, China.

    Science.gov (United States)

    Chu, Carissa E; Wu, Feng; He, Xi; Ma, Qingyan; Cheng, Yu; Cai, Weiping; Volberding, Paul; Tucker, Joseph D

    2015-01-01

    Our objective was to explore the social meaning of HIV and perceptions of an HIV cure among people who inject drugs (PWID) in Guangzhou, China, which speaks to ethical and resource challenges to development in this field. We conducted a qualitative research study using in-depth interviews. We analyzed interview transcripts from 29 PWID, eight physicians, and three social workers from an outpatient HIV clinic and two methadone maintenance treatment centers. The social meaning of HIV infection and perceptions of an HIV cure reflected patients' relationships with society, health systems, and physicians. First, HIV infection decreased perceived social worth and disrupted peer relationships. The possibility of being cured renewed patient hope for regaining physical well-being and achieving social mobility. However, the existence of a cure may not alter the HIV-related stigma due to its association with stigmatized behaviors and marginalized groups. Second, although stigma was a significant barrier to engagement in health care, hope for a cure may outweigh fears of stigma and enhance linkage to HIV testing and treatment as well as methadone services. A cure may exacerbate perceived health disparities if inaccessible to key affected populations such as PWID. The social implications of an HIV cure among this key affected population may inform the design and implementation of cure clinical trials. Careful management of patient expectations, focusing research on key affected populations, expanding HIV testing and treatment systems, improving access to harm reduction programs, and ensuring post-trial access are important considerations for HIV cure research.

  10. Short-term maraviroc exposure, a clinical approach to decide on maraviroc prescription in HIV-1-infected treatment-naïve patients

    Directory of Open Access Journals (Sweden)

    Gonzalez-Serna A

    2016-01-01

    Full Text Available Alejandro Gonzalez-Serna,1 Miguel Genebat,2 Ezequiel Ruiz-Mateos,2 Manuel Leal2 1Laboratory of Molecular Immunobiology, Hospital General Universitario Gregorio Maranon, Madrid, 2Laboratory of Immunovirology, Institute of Biomedicine of Seville, Seville, SpainWoollard and Kanmogne1 have generated an exhaustive review on maraviroc and its use in human immunodeficiency virus (HIV infection. Within their interesting dissertation, they discuss about the maraviroc clinical test (MCT, a clinical approach developed in our group in order to decide candidate patients to receive maraviroc as part of a further combined antiretroviral therapy, as an alternative to genotypic and phenotypic tropism assays.2View the original article by Woollard and Kanmogne

  11. HIV/AIDS stigma: measurement and relationships to psycho-behavioral factors in Latino gay/bisexual men and transgender women.

    Science.gov (United States)

    Molina, Y; Ramirez-Valles, J

    2013-01-01

    Despite the increased interest in HIV/AIDS stigma and its negative effects on the health and social support of people living with HIV/AIDS (PLWHA), little attention has been given to its assessment among Latino gay/ bisexual men and transgender women (GBT) living with HIV/AIDS. The purpose of this paper is twofold: to develop a multidimensional assessment of HIV/AIDS stigma for Latino GBT living with HIV/AIDS, and to test whether such stigma is related to self-esteem, safe sex self-efficacy, social support, and alcohol, and drug use. The sample included 170 HIV+ Latino GBT persons. The results revealed three dimensions of stigma: internalized, perceived, and enacted HIV/AIDS stigma. Enacted HIV/AIDS stigma comprised two domains: generalized and romantic and sexual. Generalized enacted HIV/AIDS stigma was related to most outcomes. Internalized HIV/AIDS stigma mediated the associations between generalized enacted HIV/AIDS stigma and self-esteem and safe sex self-efficacy. In addition, romantic and sexual enacted HIV/AIDS stigma significantly predicted drug use. Perceived HIV/AIDS stigma was not associated with any outcome. These findings expand the understanding of the multidimensionality of stigma and the manner in which various features impact marginalized PLWHA.

  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. HIV and aging

    Directory of Open Access Journals (Sweden)

    Edward J. Wing

    2016-12-01

    Full Text Available With the wider availability of antiretrovirals, the world's HIV population is aging. More than 10% of the 34.5 million HIV-positive individuals worldwide are over the age of 50 years and the average age continues to increase. In the USA more than 50% of the 1.3 million people with HIV are over 50 years old and by the year 2030 it is estimated that 70% will be over the age of 50 years. Although the life expectancy of HIV-positive people has increased dramatically, it still lags behind that of HIV-negative individuals. There is controversy about whether HIV itself accelerates the aging process. Elevated rates of inflammation seen in people with HIV, even if their viral loads are suppressed and their CD4 counts are preserved, are associated with greater rates of cardiovascular, renal, neurocognitive, oncological, and osteoporotic disease. These conditions increase exponentially in the elderly and will represent a major challenge for HIV patients. In addition, conditions such as geriatric syndromes including frailty are also seen at higher rates. Management of the aging HIV patient includes an emphasis on early diagnosis and treatment, preventative measures for co-morbidities, and avoiding polypharmacy. Finally, the issue of quality of life, prioritization of medical issues, and end of life care become increasingly important as the patient grows older.

  14. HIV and aging.

    Science.gov (United States)

    Wing, Edward J

    2016-12-01

    With the wider availability of antiretrovirals, the world's HIV population is aging. More than 10% of the 34.5 million HIV-positive individuals worldwide are over the age of 50 years and the average age continues to increase. In the USA more than 50% of the 1.3 million people with HIV are over 50 years old and by the year 2030 it is estimated that 70% will be over the age of 50 years. Although the life expectancy of HIV-positive people has increased dramatically, it still lags behind that of HIV-negative individuals. There is controversy about whether HIV itself accelerates the aging process. Elevated rates of inflammation seen in people with HIV, even if their viral loads are suppressed and their CD4 counts are preserved, are associated with greater rates of cardiovascular, renal, neurocognitive, oncological, and osteoporotic disease. These conditions increase exponentially in the elderly and will represent a major challenge for HIV patients. In addition, conditions such as geriatric syndromes including frailty are also seen at higher rates. Management of the aging HIV patient includes an emphasis on early diagnosis and treatment, preventative measures for co-morbidities, and avoiding polypharmacy. Finally, the issue of quality of life, prioritization of medical issues, and end of life care become increasingly important as the patient grows older. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Sex, gender and HIV.

    Science.gov (United States)

    2003-10-01

    There is an ongoing dialogue within HIV research about how HIV affects men and women differently and how they may respond to therapy differently. What is often overlooked is the difference between sex and gender. Sex is based in a person's biology. Gender is based in how society treats men and women because of their sex and how their roles and responsibilities are generally ascribed to them. Sex and gender may play a role in the differences seen between men and women living with HIV. So what are those differences and how do they impact the course of HIV in men and women? This article will attempt to answer some of those questions.

  16. Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine

    DEFF Research Database (Denmark)

    De Groot, Anne S; Levitz, Lauren; Ardito, Matthew T

    2012-01-01

    of global HIV evolution. Twenty-seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs......Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8(+) cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response...... and that are conserved in sequence and across time may represent the "Achilles' heel" of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context...

  17. Prevalence of HIV infection and the correlates among beggars in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    SeyedAhmad SeyedAlinaghi

    2013-02-01

    Full Text Available Objective: to assess the prevalence of HIV infection and the correlates among street beggars in Tehran, Iran. Methods: In a survey conducted in Tehran during 2007 to 2008, 4230 men and women beggars were collected by municipality. As a routine approach, we got serologic test for HIV. A questionnaire regarding socio-demographic and injection drug use (IDU behaviors was designed. Results: HIV prevalence was 1% (0.7 -1.3 in the study population. HIV infection was associated with older age (adjusted OR: 0.38 for >50 years, birthplace (adjusted OR: 2.06 and being IDU (adjusted OR: 8.26. Conclusions: Regarding the HIV prevalence and the correlated, we recommend harm reduction programs such as needle exchange, expanding methadone maintenance therapy and renewing education among this population.

  18. The epidemic of HIV/AIDS in developing countries; the current scenario in Pakistan.

    Science.gov (United States)

    Yousaf, Muhammad Z; Zia, Sadia; Babar, Masroor E; Ashfaq, Usman A

    2011-08-12

    HIV (Human Immunodeficiency virus) causes (acquired immunodeficiency syndrome) AIDS, in which the immune system of body totally fails to develop any defense against the foreign invaders. Infection with HIV occurs by transfer of blood, semen, and breast milk. HIV/AIDS is a global problem and it results nearly 25 million deaths worldwide. Developing countries like Pakistan have issues regarding Public Health. Currently, epidemic of HIV/AIDS is established in Pakistan and there is a threat of an expanded HIV/AIDS outbreak in the country. The major reason is that population is engaging in high-risk practices, low awareness about HIV/AIDS, and treacherous blood transfusion practices. A supplementary threat to Pakistan is India because both sharing a border and India is facing a rapidly growing HIV/AIDS epidemic. Local NGOs, National and International organizations are warning that in near future Pakistan may experiences bad situation regarding HIV/AIDS.In the present article we focused current situation of surveillance of HIV/AIDS, its virology, genotype, diagnostics, high-risk groups, reasons of vulnerability in Pakistani population, and the role of different national and international organizations in this situation.

  19. The epidemic of HIV/AIDS in developing countries; the current scenario in Pakistan

    Directory of Open Access Journals (Sweden)

    Babar Masroor E

    2011-08-01

    Full Text Available Abstract HIV (Human Immunodeficiency virus causes (acquired immunodeficiency syndrome AIDS, in which the immune system of body totally fails to develop any defense against the foreign invaders. Infection with HIV occurs by transfer of blood, semen, and breast milk. HIV/AIDS is a global problem and it results nearly 25 million deaths worldwide. Developing countries like Pakistan have issues regarding Public Health. Currently, epidemic of HIV/AIDS is established in Pakistan and there is a threat of an expanded HIV/AIDS outbreak in the country. The major reason is that population is engaging in high-risk practices, low awareness about HIV/AIDS, and treacherous blood transfusion practices. A supplementary threat to Pakistan is India because both sharing a border and India is facing a rapidly growing HIV/AIDS epidemic. Local NGOs, National and International organizations are warning that in near future Pakistan may experiences bad situation regarding HIV/AIDS. In the present article we focused current situation of surveillance of HIV/AIDS, its virology, genotype, diagnostics, high-risk groups, reasons of vulnerability in Pakistani population, and the role of different national and international organizations in this situation.

  20. Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

    Science.gov (United States)

    Vasylyeva, Tetyana I; Friedman, Samuel R; Lourenco, Jose; Gupta, Sunetra; Hatzakis, Angelos; Pybus, Oliver G; Katzourakis, Aris; Smyrnov, Pavlo; Karamitros, Timokratis; Paraskevis, Dimitrios; Magiorkinis, Gkikas

    2016-11-28

    Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

  1. Employing human rights frameworks to realize access to an HIV cure.

    Science.gov (United States)

    Meier, Benjamin Mason; Gelpi, Adriane; Kavanagh, Matthew M; Forman, Lisa; Amon, Joseph J

    2015-01-01

    The scale of the HIV pandemic - and the stigma, discrimination and violence that surrounded its sudden emergence - catalyzed a public health response that expanded human rights in principle and practice. In the absence of effective treatment, human rights activists initially sought to protect individuals at high risk of HIV infection. With advances in antiretroviral therapy, activists expanded their efforts under international law, advocating under the human right to health for individual access to treatment. As a clinical cure comes within reach, human rights obligations will continue to play a key role in political and programmatic decision-making. Building upon the evolving development and implementation of the human right to health in the global response to HIV, we outline a human rights research agenda to prepare for HIV cure access, investigating the role of human rights law in framing 1) resource allocation, 2) international obligations, 3) intellectual property and 4) freedom from coercion. The right to health is widely recognized as central to governmental, intergovernmental and non-governmental responses to the pandemic and critical both to addressing vulnerability to infection and to ensuring universal access to HIV prevention, treatment, care and support. While the advent of an HIV cure will raise new obligations for policymakers in implementing the right to health, the resolution of past debates surrounding HIV prevention and treatment may inform claims for universal access.

  2. Employing human rights frameworks to realize access to an HIV cure

    Directory of Open Access Journals (Sweden)

    Benjamin Mason Meier

    2015-11-01

    Full Text Available Introduction: The scale of the HIV pandemic – and the stigma, discrimination and violence that surrounded its sudden emergence – catalyzed a public health response that expanded human rights in principle and practice. In the absence of effective treatment, human rights activists initially sought to protect individuals at high risk of HIV infection. With advances in antiretroviral therapy, activists expanded their efforts under international law, advocating under the human right to health for individual access to treatment. Discussion: As a clinical cure comes within reach, human rights obligations will continue to play a key role in political and programmatic decision-making. Building upon the evolving development and implementation of the human right to health in the global response to HIV, we outline a human rights research agenda to prepare for HIV cure access, investigating the role of human rights law in framing 1 resource allocation, 2 international obligations, 3 intellectual property and 4 freedom from coercion. Conclusions: The right to health is widely recognized as central to governmental, intergovernmental and non-governmental responses to the pandemic and critical both to addressing vulnerability to infection and to ensuring universal access to HIV prevention, treatment, care and support. While the advent of an HIV cure will raise new obligations for policymakers in implementing the right to health, the resolution of past debates surrounding HIV prevention and treatment may inform claims for universal access.

  3. A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.

    Science.gov (United States)

    Wang, Wei; Yao, Nan; Ju, Bin; Dong, Zhihui; Cong, Zhe; Jiang, Hong; Qin, Chuan; Wei, Qiang

    2014-06-01

    Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  4. The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing.

    Science.gov (United States)

    Svicher, Valentina; Cento, Valeria; Rozera, Gabriella; Abbate, Isabella; Santoro, Maria Mercedes; Armenia, Daniele; Fabeni, Lavinia; Bruselles, Alessandro; Latini, Alessandra; Palamara, Guido; Micheli, Valeria; Rizzardini, Giuliano; Gori, Caterina; Forbici, Federica; Ippolito, Giuseppe; Andreoni, Massimo; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Capobianchi, Maria Rosaria; Perno, Carlo Federico

    2013-01-01

    The false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA). 54 HIV-1 B-subtype infected-patients (all maraviroc-naïve), with viremia >10,000copies/ml, were analyzed. HIV-tropism was assessed by V3 population-sequencing, UDPS (considering variants with >0.5% prevalence), and ESTA. By UDPS, CCR5-using variants were detected in 53/54 patients, irrespective of FPR values, and their intra-patient prevalence progressively increased by increasing the FPR obtained by V3 population-sequencing (rho = 0.75, p = 5.0e-8). Conversely, the intra-patient prevalence of CXCR4-using variants in the 54 patients analyzed progressively decreased by increasing the FPR (rho = -0.61; p = 9.3e-6). Indeed, no CXCR4-using variants were detected in 13/13 patients with FPR>60. They were present in 7/18 (38.8%) patients with FPR 20-60 (intra-patient prevalence range: 2.1%-18.4%), in 5/7 (71.4%) with FPR 10-20, in 4/6 (66.7%) with FPR 5-10, and in 10/10(100%) with FPRHIV-1 tropism determination. More sensitive methodologies (as UDPS) might be useful when V3 population-sequencing provides a FPR >20 (particularly in the range 20-60), allowing a more careful identification of patients harboring CXCR4-using variants.

  5. HIV testing preferences among long distance truck drivers in Kenya: a discrete choice experiment.

    Science.gov (United States)

    Strauss, Michael; George, Gavin; Lansdell, Emma; Mantell, Joanne E; Govender, Kaymarlin; Romo, Matthew; Odhiambo, Jacob; Mwai, Eva; Nyaga, Eston N; Kelvin, Elizabeth A

    2018-01-01

    Providing HIV testing services to truck drivers in Africa is crucial but has proven challenging. The introduction of HIV self-testing promises to provide expanded service delivery options for clients, potentially increasing demand for services and expanding coverage - especially important for high-risk and difficult-to-reach populations. This study examines the preferences regarding HIV testing service delivery models, among long distance truck drivers to identify testing services that would appeal to this population. Using a discrete choice experiment, this study examines the drivers of choice regarding HIV counselling and testing among 305 truck drivers recruited from two roadside wellness clinics along major trucking routes in Kenya. Participants made trade-offs between characteristics of HIV testing service delivery models by making hypothetical choices in a series of paired HIV testing scenarios. Conditional logit models were used to identify the HIV testing characteristics driving the selection of preferred scenarios, as well as determine whether preferences interact with individual characteristics - especially HIV testing history. Participants preferred free, provider-administered HIV testing at a roadside clinic, using a finger-prick test, with in-person counselling, undertaken in the shortest possible time. The strongest driver of choice was the cost of the test. Those who had never tested previously preferred oral testing and telephonic counselling, while those who were not regular testers favoured clinic based - over self-testing. The results of this study indicate that for the majority of participants - most of whom had tested before - the existing services offered at roadside clinics were the preferred service delivery model. The introduction of oral self-testing increases the options available to truck drivers and may even improve testing uptake for some, especially among those who have never tested before. However, these findings suggest the impact

  6. Maturation of HIV envelope glycoprotein precursors by cellular endoproteases.

    Science.gov (United States)

    Moulard, M; Decroly, E

    2000-11-10

    The entry of enveloped viruses into its host cells is a crucial step for the propagation of viral infection. The envelope glycoprotein complex controls viral tropism and promotes the membrane fusion process. The surface glycoproteins of enveloped viruses are synthesized as inactive precursors and sorted through the constitutive secretory pathway of the infected cells. To be infectious, most of the viruses require viral envelope glycoprotein maturation by host cell endoproteases. In spite of the strong variability of primary sequences observed within different viral envelope glycoproteins, the endoproteolytical cleavage occurs mainly in a highly conserved domain at the carboxy terminus of the basic consensus sequence (Arg-X-Lys/Arg-Arg downward arrow). The same consensus sequence is recognized by the kexin/subtilisin-like serine proteinases (so called convertases) in many cellular substrates such as prohormones, proprotein of receptors, plasma proteins, growth factors and bacterial toxins. Therefore, several groups of investigators have evaluated the implication of convertases in viral envelope glycoprotein cleavage. Using the vaccinia virus overexpression system, furin was first shown to mediate the proteolytic maturation of both human immunodeficiency virus (HIV-1) and influenza virus envelope glycoproteins. In vitro studies demonstrated that purified convertases directly and specifically cleave viral envelope glycoproteins. Although these studies suggested the participation of several enzymes belonging to the convertases family, recent data suggest that other protease families may also participate in the HIV envelope glycoprotein processing. Their role in the physiological maturation process is still hypothetical and the molecular mechanism of the cleavage is not well documented. Crystallization of the hemagglutinin precursor (HA0) of influenza virus allowed further understanding of the molecular interaction between viral precursors and the cellular endoproteases

  7. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

    Science.gov (United States)

    Simon, Viviana; Ho, David D; Karim, Quarraisha Abdool

    2010-01-01

    The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Research has deepened our understanding of how the virus replicates, manipulates, and hides in an infected person. Although our understanding of pathogenesis and transmission dynamics has become more nuanced and prevention options have expanded, a cure or protective vaccine remains elusive. Antiretroviral treatment has transformed AIDS from an inevitably fatal condition to a chronic, manageable disease in some settings. This transformation has yet to be realised in those parts of the world that continue to bear a disproportionate burden of new HIV-1 infections and are most a% ected by increasing morbidity and mortality. This Seminar provides an update on epidemiology, pathogenesis, treatment, and prevention interventions pertinent to HIV-1. PMID:16890836

  8. Expanding Greenland’s Glacial Record

    DEFF Research Database (Denmark)

    Bjørk, Anders Anker

    Mass loss from the Greenland Ice Sheet and adjecent glaciers and ice caps has accelerated within the last decades, and these changes are accurately observed using a variety of different data products. However, the observational era is relatively short offering little insight into past dynamics....... On order to expand the glacial history of Greenland, this thesis explores physical and geological archives for evidence of the glaciers’ past response to climatic variations. Using aerial photographs, the dynamic history of the Greenland Ice Sheet is extended back to 1900 C.E. Glacier changes covering...

  9. Expanding the Bethe/Gauge dictionary

    Science.gov (United States)

    Bullimore, Mathew; Kim, Hee-Cheol; Lukowski, Tomasz

    2017-11-01

    We expand the Bethe/Gauge dictionary between the XXX Heisenberg spin chain and 2d N = (2, 2) supersymmetric gauge theories to include aspects of the algebraic Bethe ansatz. We construct the wave functions of off-shell Bethe states as orbifold defects in the A-twisted supersymmetric gauge theory and study their correlation functions. We also present an alternative description of off-shell Bethe states as boundary conditions in an effective N = 4 supersymmetric quantum mechanics. Finally, we interpret spin chain R-matrices as correlation functions of Janus interfaces for mass parameters in the supersymmetric quantum mechanics.

  10. FOAM: Expanding the horizons of climate modeling

    Energy Technology Data Exchange (ETDEWEB)

    Tobis, M.; Foster, I.T.; Schafer, C.M. [and others

    1997-10-01

    We report here on a project that expands the applicability of dynamic climate modeling to very long time scales. The Fast Ocean Atmosphere Model (FOAM) is a coupled ocean atmosphere model that incorporates physics of interest in understanding decade to century time scale variability. It addresses the high computational cost of this endeavor with a combination of improved ocean model formulation, low atmosphere resolution, and efficient coupling. It also uses message passing parallel processing techniques, allowing for the use of cost effective distributed memory platforms. The resulting model runs over 6000 times faster than real time with good fidelity, and has yielded significant results.

  11. Expanding Slayer Statutes to Elder Abuse.

    Science.gov (United States)

    Piel, Jennifer

    2015-09-01

    Common law has a dictum that people must not benefit from their crimes. In years past, states have enacted slayer rules to prevent killers from inheriting from their victims. The specific criteria and applicability of slayer rules vary by jurisdiction. Recently, several states, including Washington, have expanded their slayer rules to disqualify persons from inheriting if they have been involved in abuse or financial exploitation of the deceased. Reviewed herein are the abuse disinheritance laws, the relationship of the laws to concepts of testamentary capacity and undue influence, and the relevance to forensic psychiatric evaluations. © 2015 American Academy of Psychiatry and the Law.

  12. Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition.

    Science.gov (United States)

    Hayes, Peter J; Cox, Josephine H; Coleman, Adam R; Fernandez, Natalia; Bergin, Philip J; Kopycinski, Jakub T; Nitayaphan, Sorachai; Pitisuttihum, Punnee; de Souza, Mark; Duerr, Ann; Morgan, Cecilia; Gilmour, Jill W

    2016-07-17

    The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers. Adenovirus serotype 5 (Ad5)-based regimens MRKAd5 and VRC DNA/Ad5, designed to elicit HIV-1-specific T cells, are immunogenic but failed to prevent infection or impact on viral loads in volunteers infected subsequently. Failure may be due in part to a lack of CD8 T cells with effective antiviral functions. An in-vitro viral inhibition assay tested the ability of bispecific antibody expanded CD8 T cells from peripheral blood mononuclear cells to inhibit replication of a multiclade panel of HIV-1 isolates in autologous CD4 T cells. HIV-1 proteins recognized by CD8 T cells were assessed by IFNγ enzyme-linked immunospot assay. Ad5-based regimens elicited CD8 T cells that inhibited replication of HIV-1 IIIB isolate with more limited inhibition of other isolates. IIIB isolate Gag and Pol genes have high sequence identities (>96%) to vector HIV-1 gene inserts, and these were the predominant HIV-1 proteins recognized by CD8 T cells. Virus inhibition breadth was greater in antiretroviral naïve HIV-1-infected volunteers naturally controlling viremia (plasma viral load elicited by the ALVAC/AIDSVAX regimen. The Ad5-based regimens, although immunogenic, elicited CD8 T cells with limited HIV-1-inhibition breadth. Effective T-cell-based vaccines should presumably elicit broader HIV-1-inhibition profiles. The viral inhibition assay can be used in vaccine design and to prioritize promising candidates with greater inhibition breadth for further clinical trials.

  13. Pilot Integration of HIV Screening and Healthcare Settings with Multi- Component Social Network and Partner Testing for HIV Detection.

    Science.gov (United States)

    Rentz, Michael F; Ruffner, Andrew H; Ancona, Rachel M; Hart, Kimberly W; Kues, John R; Barczak, Christopher M; Lindsell, Christopher J; Fichtenbaum, Carl J; Lyons, Michael S

    2017-11-23

    Healthcare settings screen broadly for HIV. Public health settings use social network and partner testing ("Transmission Network Targeting (TNT)") to select high-risk individuals based on their contacts. HIV screening and TNT systems are not integrated, and healthcare settings have not implemented TNT. The study aimed to evaluate pilot implementation of multi-component, multi-venue TNT in conjunction with HIV screening by a healthcare setting. Our urban, academic health center implemented a TNT program in collaboration with the local health department for five months during 2011. High-risk or HIV positive patients of the infectious diseases clinic and emergency department HIV screening program were recruited to access social and partner networks via compensated peer-referral, testing of companions present with them, and partner notification services. Contacts became the next-generation index cases in a snowball recruitment strategy. The pilot TNT program yielded 485 HIV tests for 482 individuals through eight generations of recruitment with five (1.0%; 95% CI = 0.4%, 2.3%) new diagnoses. Of these, 246 (51.0%; 95% CI = 46.6%, 55.5%) reported that they had not been tested for HIV within the last 12 months and 383 (79.5%; 95% CI = 75.7%, 82.9%) had not been tested by the existing ED screening program within the last five years. TNT complements population screening by more directly targeting high-risk individuals and by expanding the population receiving testing. Information from existing healthcare services could be used to seed TNT programs, or TNT could be implemented within healthcare settings. Research evaluating multi-component, multi-venue HIV detection is necessary to maximize complementary approaches while minimizing redundancy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. HIV-discordant couples

    African Journals Online (AJOL)

    Winnie

    2006-06-02

    Jun 2, 2006 ... and Gynecology have noted that assisted reproductive technologies should not be withheld from HIV-infected infertile couples merely on the grounds of HIV serostatus.26. However, ethical controversies in this area remain. Adequate preconception counselling to establish the stability of the discordant ...

  15. Psychoneuroimmunology and HIV-1.

    Science.gov (United States)

    Antoni, Michael H.; And Others

    1990-01-01

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

  16. HIV and AIDS

    Science.gov (United States)

    ... one of the most serious, deadly diseases in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type of defense cell in the body called a CD4 helper lymphocyte (pronounced: LIM-foe- ...

  17. HIV and childhood cancer

    African Journals Online (AJOL)

    as WHO stage IV or CDC category C conditions. The HIV- ... naïve HIV-infected children will develop cancer annually.6 This risk declines to 76 per .... developing world. One adult study from. Zimbabwe suggested that patients treated with oral etoposide had a better quality of life than patients treated with infusional agents or ...

  18. The HIV Airway

    African Journals Online (AJOL)

    Adele

    been reported to result in airway obstruction. Conditions not limited to immunocomromised states such as epiglottitis, retropharyngeal abcesses, mediastinal masses and. Ludwig's angina are seen, with increased severity, in HIV in- fected individuals. Knowledge of a patients' HIV status may alert one to potential.

  19. HIV Viral Load

    Science.gov (United States)

    ... online at http://www.aidsinfonet.org/fact_sheets/view/125. Accessed February 2009. (Updated 2011 January 10). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, Plasma HIV RNA Testing. AIDSinfo On-line information]. ...

  20. HIV and Hepatitis C

    Science.gov (United States)

    ... during sex. The risk of HCV infection through sexual contact is low, but the risk increases in people with HIV. Condoms also reduce the risk of HIV transmission and infection with other sexually transmitted diseases such as gonorrhea and syphilis . Should people with ...