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Sample records for sustained viral suppression

  1. Tobacco Use and Sustained Viral Suppression in Youth Living with HIV.

    Science.gov (United States)

    Gamarel, Kristi E; Westfall, Andrew O; Lally, Michelle A; Hosek, Sybil; Wilson, Craig M

    2017-09-26

    Tobacco has been associated with worse HIV disease progression in adult samples of people living with HIV; however, studies have yet to examine these effects in youth living with HIV (YLWH). This study examined the association between tobacco smoking behaviors and sustained viral suppression among a sample of 820 YLWH who were recruited through the Adolescent Medicine Trials Network for HIV Interventions. Participants completed a cross-sectional survey and then staff abstracted viral suppression data from medical records for up to 26 weeks prior to enrollment. Overall, 20.4% of youth reported daily or almost daily tobacco use. In multivariable analyses, older age and daily or almost daily tobacco smoking, and ART adherence remained statistically significant in predicting sustained viral suppression over the study period. These findings underscore the need for tobacco screening and interventions in HIV care settings in order to identify youth in need of additional smoking cessation services.

  2. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Tracy R Glass

    Full Text Available BACKGROUND: Good adherence to antiretroviral therapy (ART is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. METHODS: Eligible individuals were Caucasians treated with efavirenz (EFV and/or boosted lopinavir (LPV/r with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6 and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2. Viral suppression was defined as having HIV-1 RNA 1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR 0.11, 95% confidence interval (CI: 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94. In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56. CONCLUSIONS: The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

  3. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy.

    Science.gov (United States)

    Glass, Tracy R; Rotger, Margalida; Telenti, Amalio; Decosterd, Laurent; Csajka, Chantal; Bucher, Heiner C; Günthard, Huldrych F; Rickenbach, Martin; Nicca, Dunja; Hirschel, Bernard; Bernasconi, Enos; Wandeler, Gilles; Battegay, Manuel; Marzolini, Catia

    2012-01-01

    Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA 1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56). The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

  4. Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression.

    Science.gov (United States)

    Rojas, Jhon; Blanco, José L; Marcos, María A; Lonca, Montserrat; Tricas, Amparo; Moreno, Laura; Gonzalez-Cordon, Ana; Torres, Berta; Mallolas, Josep; Garcia, Federico; Gatell, Jose M; Martinez, Esteban

    2016-07-01

    We reviewed the 24 week outcomes of HIV-infected patients from our hospital who had their ART switched to dolutegravir monotherapy on an individual clinical basis. Retrospective hospital database assessment of virally suppressed patients in whom the treating physician had switched to 50 mg of dolutegravir once daily due to one or more of the following reasons: antiretroviral-related adverse effects; comorbidities; risk of interactions; or archived resistance. Patients had ≥24 weeks of follow-up. Population, virological and immunological responses and safety and tolerability are described. Thirty-three (22 on PIs, of whom 18 had ritonavir-boosted PI monotherapy) patients were identified: median (IQR) age of 56 (50-62) years, 55% women, median (IQR) of 19 (17-23) years of known HIV infection, 39% prior AIDS events, median (IQR) of 8 (4-13) years with undetectable plasma HIV-1 RNA and median (IQR) CD4 cell count of 596 (420-843) cells/mm(3). Twenty-five (76%) patients had antiretroviral-related adverse effects, 32 (97%) patients had comorbidities, 28 (85%) patients had risk of interactions and 16 (48%) patients had archived resistance. One patient with suboptimal adherence had low-level virological failure through weeks 4-24. HIV RNA genotypic resistance tests detected no integrase mutations at weeks 4 and 24, but 118R was detected in 7% of the integrated HIV DNA at 24 weeks. Patients had significant median decreases in triglycerides (-117 mg/dL), total cholesterol (-36 mg/dL), the total cholesterol/HDL cholesterol ratio (-0.7) and high-sensitivity C-reactive protein (-0.05 mg/dL) (P ≤ 0.007), although the Chronic Kidney Disease Epidemiology Collaboration equation also decreased (-7.1 mL/min) (P < 0.0001). These data suggest the efficacy of dolutegravir monotherapy as a maintenance strategy to be further confirmed in randomized clinical trials. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  5. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo.

    Directory of Open Access Journals (Sweden)

    Upkar S Gill

    2016-08-01

    Full Text Available NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are 'primed' with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(tides (sequential NUC therapy, an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB.

  6. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  7. Hodgkin lymphoma is as common as non-Hodgkin lymphoma in HIV-positive patients with sustained viral suppression and limited immune deficiency: a prospective cohort study.

    Science.gov (United States)

    Hoffmann, C; Hentrich, M; Gillor, D; Behrens, G; Jensen, B; Stoehr, A; Esser, S; van Lunzen, J; Krznaric, I; Müller, M; Oette, M; Hensel, M; Thoden, J; Fätkenheuer, G; Wyen, C

    2015-04-01

    The incidence of HIV-related non-Hodgkin lymphoma (NHL) but not that of Hodgkin lymphoma (HL) has been declining. The aim of the study was to compare HIV-infected patients with NHL and HL with respect to antiretroviral therapy (ART) exposure at the time of lymphoma diagnosis. HIV-infected patients with NHL and HL included in a prospective multicentre cohort study since January 2005 were compared with respect to ART exposure and viral load at the time of lymphoma diagnosis. As of 31 December 2012, data for 329 patients with NHL and 86 patients with HL from 31 participating centres were available. Patients with HL were more likely to be on ART (73.5% vs. 39.1%, respectively; P  12 months and a CD4 cell count of > 200 cells/μL. Of note, 45.8% of all patients with NHL were not currently on ART and had a CD4 count of < 350 cells/μL. This prospective cohort study shows that HL was as common as NHL in patients with sustained viral suppression and limited immune deficiency. In contrast to NHL, the majority of patients with HL were on effective ART, suggesting that ART provides insufficient protection from developing HL. The high proportion of untreated patients with NHL suggests missed opportunities for earlier initiation of ART. © 2014 British HIV Association.

  8. Viral Innovation, Sustainability, and Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Eskildsen, Jacob Kjær

    for these models include Biophysical/Environmental, Business/Economic, and Societal dimensions with the BEST model adding a Technological dimension that refers predominantly to infrastructure, that is, to the built-environment. Integration across these sustainability dimensions is challenging, but can......Enterprises strive to be economically sustainable. In doing so, they either contribute to or detract from environmental and social sustainability. Sustainability is hence multi-dimensional with formulations that include the familiar triple-bottom-line and BEST models. Any assessment regimen...... what is henceforth called “viral innovation”. Evidence of growing global emphasis on environmental and social sustainability is provided by the United Nations Global Compact (http://www.unglobalcompact.org/), the Pearl Initiative in the Middle East (http...

  9. Novel use of surveillance data to detect HIV-infected persons with sustained high viral load and durable virologic suppression in New York City.

    Directory of Open Access Journals (Sweden)

    Arpi S Terzian

    Full Text Available BACKGROUND: Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL. METHODS/PRINCIPAL FINDINGS: Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. CONCLUSIONS/SIGNIFICANCE: Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.

  10. Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Pedersen, Court; Madsen, Helle D

    2017-01-01

    A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was ......A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis...

  11. HIV Care Saves Lives: Viral Suppression is Key PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2014-11-25

    This 60 second Public Service Announcement is based on the December 2014 Vital Signs. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 11/25/2014.

  12. Optimization of human immunodeficiency virus treatment during incarceration: viral suppression at the prison gate.

    Science.gov (United States)

    Meyer, Jaimie P; Cepeda, Javier; Wu, Johnny; Trestman, Robert L; Altice, Frederick L; Springer, Sandra A

    2014-05-01

    environment and, when combined with simple well-tolerated ART regimens, can result in viral suppression during incarceration. In the absence of important and effective community-based resources, incarceration can be an opportunity of last resort to initiate continuous ART for individual health and, following the "treatment as prevention" paradigm, potentially reduce the likelihood of HIV transmission to others after release if continuity of HIV care is sustained.

  13. Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

    NARCIS (Netherlands)

    Engsig, Frederik N.; Zangerle, Robert; Katsarou, Olga; Dabis, Francois; Reiss, Peter; Gill, John; Porter, Kholoud; Sabin, Caroline; Riordan, Andrew; Fätkenheuer, Gerd; Gutiérrez, Félix; Raffi, Francois; Kirk, Ole; Mary-Krause, Murielle; Stephan, Christoph; de Olalla, Patricia Garcia; Guest, Jodie; Samji, Hasina; Castagna, Antonella; D'Arminio Monforte, Antonella; Skaletz-Rorowski, Adriane; Ramos, Jose; Lapadula, Giuseppe; Mussini, Cristina; Force, Lluís; Meyer, Laurence; Lampe, Fiona; Boufassa, Faroudy; Bucher, Heiner C.; de Wit, Stéphane; Burkholder, Greer A.; Teira, Ramon; Justice, Amy C.; Sterling, Tim R.; M Crane, Heidi; Gerstoft, Jan; Grarup, Jesper; May, Margaret; Chêne, Geneviève; Ingle, Suzanne M.; Sterne, Jonathan; Obel, Niels; Burkholder, Greer; Justice, Amy; R Sterling, Tim; Crane, Heidi M.; Boulle, Andrew; Brodt, Hans-Reinhard; Casabona, Jordi; Cavassini, Matthias; Costagliola, Dominique; Dabis, François; del Amo, Julia; van Sighem, Ard; Hans-Ulrich Haerry, David; Hogg, Robert; Mocroft, Amanda; Kitahata, Mari; Saag, Michael; Williams, Matthew; Ingle, Suzanne; Touloumi, Giota; Warszawski, Josiane; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Wit, Ferdinand; Prins, Maria; Gibb, Diana; Thorne, Claire; Pérez-Hoyos, Santiago; Hamouda, Osamah; Gussenheimer-Bartmeyer, Barbara; Noguera-Julian, Antoni; Antinori, Andrea; Brockmeyer, Norbert; Ramos, José; Battegay, Manuel; Rauch, Andri; Tookey, Pat; Miró, Jose M.; de Wit, Stephane; Goetghebuer, Tessa; Torti, Carlo; Garrido, Myriam; Judd, Ali; Conejo, Pablo Rojo; Haerry, David; Weller, Ian; D'Arminio-Monforte, Antonella; Colin, Céline; Schwimmer, Christine; Termote, Monique; Kjaer, Jesper; Campbell, Maria; Raben, Dorthe; Bohlius, Julia; Bouteloup, Vincent; Bucher, Heiner; Cozzi-Lepri, Alessandro; Dorrucci, Maria; Egger, Matthias; Engsig, Frederik; Furrer, Hansjakob; Lambotte, Olivier; Lewden, Charlotte; Lodi, Sara; Lodwick, Rebbeca; Matheron, Sophie; Miro, Jose; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Reekie, Joanne; Scherrer, Alexandra; Smit, Colette; Thiebaut, Rodolphe; Wittkop, Linda

    2014-01-01

    Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained

  14. Towards Sustainability in Viral Marketing with User Engaging Supporting Campaigns

    Directory of Open Access Journals (Sweden)

    Jarosław Jankowski

    2017-12-01

    Full Text Available While viral marketing has captured substantial academic and professional interest, the processes that underpin successful viral marketing campaigns remain poorly understood. High competition and pressure for successful campaigns lead to strategies based on persuasion, unsolicited messages, and other techniques that negatively affect brand perception. The need for more sustainable strategies with a limited negative impact on web users is observed. Therefore, the current study examines the effectiveness of viral marketing and a supporting campaign, where the main goal was to increase user engagement and overall campaign performance. Supporting campaigns were evaluated, to determine whether they enhanced viral activity, but without the need for high persuasion or intrusive techniques. Results showed that supporting actions could be integrated with lower performing campaigns to increase their effectiveness. Apart from the main scientific goal that is presented, the study demonstrates how virtual worlds can provide a laboratory-like environment for identifying the processes that underpin viral marketing.

  15. Factors associated with 10 years of continuous viral load suppression on HAART.

    Science.gov (United States)

    Bello, Kathryn J; Mesner, Octavio; O'Bryan, Thomas A; Won, Seung Hyun; Lalani, Tahaniyat; Ganesan, Anuradha; Agan, Brian K; Okulicz, Jason F

    2016-07-22

    The principal goal of HAART is sustained viral load (VL) suppression resulting in immune reconstitution and improved HIV outcomes. We studied the factors associated with 10 years of continuous VL suppression on HAART in the US Military HIV Natural History Study. Participants with continuous VL suppression (CS, n = 149) were compared to those who did not have continuous viral load suppression (NCS, n = 127) for ≥10 years on HAART. Factors associated with >10 years of VL suppression were evaluated by multivariate logistic regression. Additionally, association between CS and CD4 reconstitution was analyzed with a mixed effects model. Compared to NCS participants, a lower proportion of CS participants started HAART in the early HAART era (66 vs 90 %, for years 1996-1999; p < 0.001) and had less antiretroviral use prior to HAART (37 vs 83 %; p < 0.001). At initial HAART, the median CD4 cell count was higher and VL was lower for CS compared to NCS participants (375 cells/uL [256, 499] vs 261 cells/uL [146, 400]; p < 0.001 and 4.4 log10 copies/mL [3.5, 4.9] vs 4.5 log10 copies/mL [3.8, 5.0]; p = 0.048, respectively). New AIDS events were lower during HAART (5 vs 13 %; p = 0.032) and post-HAART CD4 trajectories were greater for the CS compared to NCS group. Factors negatively associated with ≥10 years of VL suppression included log10 VL at first HAART (OR 0.61, 95 % CI 0.4, 0.92; p = 0.020) and antiretroviral use prior to HAART (OR 0.16, 95 % CI 0.06, 0.38; p < .001). Sustained VL suppression is a key to long-term health in HIV-infected patients, as demonstrated by the lower proportion of AIDS events observed 10 years after HAART initiation. The current use of more potent and well-tolerated regimens may mitigate the negative factors of pre-HAART VL and prior ARV use encountered by treatment initiated in the early HAART era.

  16. Sustainable HIV Treatment in Africa through Viral Load-Informed Differentiated Care

    Science.gov (United States)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens; Eaton, Jeff; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara; Musanhu, Christine Chiedza; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy; Revill, Paul

    2016-01-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests. PMID:26633768

  17. Financial Incentives for Linkage to Care and Viral Suppression Among HIV-Positive Patients

    Science.gov (United States)

    Donnell, Deborah; Beauchamp, Geetha; Hall, H. Irene; Torian, Lucia V.; Zingman, Barry; Lum, Garret; Kharfen, Michael; Elion, Richard; Leider, Jason; Gordin, Fred M.; Elharrar, Vanessa; Burns, David; Zerbe, Allison; Gamble, Theresa; Branson, Bernard

    2017-01-01

    Importance Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits. Objective To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. Design, Setting, and Participants A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. Interventions Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. Main Outcomes and Measures Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (<400 copies/mL), assessed at each calendar quarter. Outcomes assessed through laboratory test results reported to the National HIV Surveillance System. Results A total of 1061 coupons were dispensed for linkage to care at 18 financial incentive test sites and 39 359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not

  18. Effect of transient versus sustained activation on interocular suppression.

    Science.gov (United States)

    Nichols, David F; Wilson, Hugh R

    2009-01-01

    Switches in perceptual dominance resulting from either binocular rivalry or flash suppression likely involve some mechanism of interocular suppression, although it is unclear from past research whether different mechanisms are involved in the two cases. Using monocular, centrally fixated sinusoidal gratings surrounded by contiguous annuli of rivalrous gratings, suppression of the entire central grating was possible using either technique. However, the magnitude of the suppression was unaffected by the presence of an ipsilateral surround for flash suppression, yet, for binocular rivalry, suppression no longer occurred when the surrounds were fusible. Nevertheless, computational modeling demonstrates that the differences between the techniques may be attributable to the sustained versus transient stimulation of the contralateral surround, with the magnitude of the suppression proportional to the activation of the contralateral surround. Consistent with this, suppression extends over a greater distance at the onset of the contralateral surround than during sustained rivalry. Therefore, it is likely that perceptual dominance in both binocular rivalry and flash suppression is based on the same mechanism of interocular suppression.

  19. The HIV Care Continuum: Changes over Time in Retention in Care and Viral Suppression.

    Directory of Open Access Journals (Sweden)

    Baligh R Yehia

    Full Text Available The HIV care continuum (diagnosis, linkage to care, retention in care, receipt of antiretroviral therapy (ART, viral suppression has been used to identify opportunities for improving the delivery of HIV care. Continuum steps are typically calculated in a conditional manner, with the number of persons completing the prior step serving as the base population for the next step. This approach may underestimate the prevalence of viral suppression by excluding patients who are suppressed but do not meet standard definitions of retention in care. Understanding how retention in care and viral suppression interact and change over time may improve our ability to intervene on these steps in the continuum.We followed 17,140 patients at 11 U.S. HIV clinics between 2010-2012. For each calendar year, patients were classified into one of five categories: (1 retained/suppressed, (2 retained/not-suppressed, (3 not-retained/suppressed, (4 not-retained/not-suppressed, and (5 lost to follow-up (for calendar years 2011 and 2012 only. Retained individuals were those completing ≥ 2 HIV medical visits separated by ≥ 90 days in the year. Persons not retained completed ≥ 1 HIV medical visit during the year, but did not meet the retention definition. Persons lost to follow-up had no HIV medical visits in the year. HIV viral suppression was defined as HIV-1 RNA ≤ 200 copies/mL at the last measure in the year. Multinomial logistic regression was used to determine the probability of patients' transitioning between retention/suppression categories from 2010 to 2011 and 2010 to 2012, adjusting for age, sex, race/ethnicity, HIV risk factor, insurance status, CD4 count, and use of ART.Overall, 65.8% of patients were retained/suppressed, 17.4% retained/not-suppressed, 10.0% not-retained/suppressed, and 6.8% not-retained/not-suppressed in 2010. 59.5% of patients maintained the same status in 2011 (kappa=0.458 and 53.3% maintained the same status in 2012 (kappa=0.437.Not

  20. Beyond viral suppression of HIV - the new quality of life frontier.

    Science.gov (United States)

    Lazarus, Jeffrey V; Safreed-Harmon, Kelly; Barton, Simon E; Costagliola, Dominique; Dedes, Nikos; Del Amo Valero, Julia; Gatell, Jose M; Baptista-Leite, Ricardo; Mendão, Luís; Porter, Kholoud; Vella, Stefano; Rockstroh, Jürgen Kurt

    2016-06-22

    In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities.

  1. Carbon monoxide and biliverdin suppress bovine viral diarrhoea virus replication.

    Science.gov (United States)

    Ma, Zhiqian; Pu, Fengxing; Zhang, Xiaobin; Yan, Yunhuan; Zhao, Lijuan; Zhang, Angke; Li, Na; Zhou, En-Min; Xiao, Shuqi

    2017-12-01

    Bovine viral diarrhoea virus (BVDV) causes significant economic losses to the cattle industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) can inhibit BVDV replication via an unknown molecular mechanism. To elucidate the mechanism involved, we assess whether the HO-1 downstream metabolites carbon monoxide (CO), biliverdin (BV) and iron affect BVDV replication. We treated Madin-Darby bovine kidney (MDBK) cells with an exogenous CO donor, CORM-2. We found that CORM-2 but not its inactive form (iCORM-2) inhibited BVDV replication in a dose-dependent and time duration-dependent manner, suggesting a CO-specific mediation of the CORM-2 antiviral effect. Direct incubation of BVDV with high-dose CORM-2 reduced virus titres, suggesting that CORM-2 attenuates BVDV growth by both physically inactivating virus particles in the extracellular environment and affecting intracellular BVDV replication, but mainly via an intracellular mechanism. Exogenous BV treatment, both post-infection and co-incubation with BVDV, inhibited BVDV replication in a dose-dependent manner, indicating that BV has potent antiviral activity against BVDV. Direct incubation of BVDV with BV had no significant effect on virus titres, indicating that BV is not virucidal and attenuates BVDV growth by affecting intracellular BVDV replication. Furthermore, BV was found to affect BVDV penetration but not attachment. However, increased iron via addition of FeCl3 did not interfere with BVDV replication. Collectively, the results of the present study demonstrate that the HO-1 metabolites BV and CO, but not iron, inhibit BVDV replication. These findings not only provide new insights into the molecular mechanism of HO-1 inhibition of BVDV replication but also suggest potential new control measures for future BVDV infection.

  2. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

    Directory of Open Access Journals (Sweden)

    Sandra A Springer

    Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  3. Viral suppression of multiple escape mutants by de novo CD8(+) T cell responses in a human immunodeficiency virus-1 infected elite suppressor.

    Science.gov (United States)

    O'Connell, Karen A; Hegarty, Robert W; Siliciano, Robert F; Blankson, Joel N

    2011-08-03

    Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he developed proliferative, de novo CTL responses that suppressed replication of each of these variants. These responses, in combination with low viral fitness of each variant, may contribute to sustained elite control in this ES.

  4. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....

  5. Brachial amyotrophic diplegia in the setting of complete HIV viral load suppression.

    Science.gov (United States)

    Cachia, David; Izzy, Saef; Ionete, Carolina; Salameh, Johnny

    2012-12-06

    Brachial amyotrophic diplegia (BAD) is a rare segmental form of motor neuron disease which presents with asymmetric lower motor neuron weakness largely confined to the upper extremities (UE). In the case being reported, a 62-year-old gentleman on antiretroviral treatment since 1993, presented with left-arm weakness in 2007 that quickly progressed to involve the right arm. Complete HIV-viral load suppression had been achieved since 2003. Examination revealed lower motor neuron weakness in both UEs, worse proximally than distally and normal strength in the lower extremities (LEs). Nerve conduction studies showed reduced amplitudes of bilateral median and ulnar nerves' motor responses. Needle electromyography of bilateral UE showed active and chronic denervation/reinnervation changes with normal findings in both LEs. MRI of the cervical spine showed cord atrophy. This is the first case report describing a patient who presented with BAD in the setting of complete HIV-viral load suppression for many years.

  6. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

    Science.gov (United States)

    Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

    2010-12-15

    Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

  7. Vital Signs-HIV Care Saves Lives: Viral Suppression is Key

    Centers for Disease Control (CDC) Podcasts

    2014-11-25

    This podcast is based on the December 2014 CDC Vital Signs report. For people living with HIV, Viral suppression is critical. By getting tested and taking HIV medicines, individuals living with HIV can achieve very low levels of HIV in the body.  Created: 11/25/2014 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/25/2014.

  8. Financial Incentives for Linkage to Care and Viral Suppression Among HIV-Positive Patients: A Randomized Clinical Trial (HPTN 065).

    Science.gov (United States)

    El-Sadr, Wafaa M; Donnell, Deborah; Beauchamp, Geetha; Hall, H Irene; Torian, Lucia V; Zingman, Barry; Lum, Garret; Kharfen, Michael; Elion, Richard; Leider, Jason; Gordin, Fred M; Elharrar, Vanessa; Burns, David; Zerbe, Allison; Gamble, Theresa; Branson, Bernard

    2017-08-01

    Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits. To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (incentive test sites and 39 359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not previously consistently virally suppressed, the proportion virally suppressed was 4.9% higher (95% CI, 1.4%-8.5%; P = .007) at financial incentive sites. In addition, continuity in care was 8.7% higher (95% CI, 4.2%-13.2%; P incentive sites. Financial incentives, as used in this study (HPTN 065), significantly increased viral

  9. Cognitive change trajectories in virally suppressed HIV-infected individuals indicate high prevalence of disease activity.

    Science.gov (United States)

    Gott, Chloe; Gates, Thomas; Dermody, Nadene; Brew, Bruce J; Cysique, Lucette A

    2017-01-01

    The longitudinal rate and profile of cognitive decline in persons with stable, treated, and virally suppressed HIV infection is not established. To address this question, the current study quantifies the rate of cognitive decline in a cohort of virally suppressed HIV+ persons using clinically relevant definitions of decline, and determine cognitive trajectories taking into account historical and baseline HAND status. Ninety-six HIV+ (clinically stable and virally undetectable) and 44 demographically comparable HIV- participants underwent standard neuropsychological testing at baseline and 18-months follow-up. We described clinically relevant cognitive trajectories based on standard definitions of historical and baseline HAND status and cognitive decline. Historical, moderate to severe HAND was formally diagnosed at the start of the cART era in 15/96 participants based on clinical neurological and neuropsychological assessment. The same standard of care has been applied to all participants at St. Vincent's Hospital Infectious Disease Department for the duration of their HIV infection (median of 20 years). Relative to HIV- controls (4.5%), 14% of HIV+ participants declined (p = .11), they also scored significantly lower on the global change score (p = .03), processing speed (p = .02), and mental flexibility/inhibition (p = .02) domains. Having HAND at baseline significantly predicted cognitive decline at follow up (p = .005). We determined seven clinically relevant cognitive trajectories taking into account whether participant has a history of HAND prior to study entry (yes/no); their results on the baseline assessment (baseline impairment: yes/no) and their results on the 18-month follow up (decline or stable) which in order of prevalence were: 1) No HAND history, no baseline impairment, 18-month follow-up stable (39%), 2) No HAND history, baseline impairment, 18-month follow-up stable (35%), 3) History of HAND; baseline impairment, 18-month follow-up stable (9%) 4

  10. Adenovirus-encoding virus-associated RNAs suppress HDGF gene expression to support efficient viral replication.

    Directory of Open Access Journals (Sweden)

    Saki Kondo

    Full Text Available Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs, are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth.

  11. Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

    Science.gov (United States)

    Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

  12. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

    Science.gov (United States)

    Cheng, Liang; Yu, Haisheng; Li, Guangming; Li, Feng; Ma, Jianping; Li, Jingyun; Chi, Liqun; Zhang, Liguo

    2017-01-01

    The direct link between sustained type I interferon (IFN-I) signaling and HIV-1–induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1–induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1–induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1–specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells. PMID:28614789

  13. Trends in Racial and Ethnic Disparities in Antiretroviral Therapy Prescription and Viral Suppression in the United States, 2009-2013.

    Science.gov (United States)

    Beer, Linda; Bradley, Heather; Mattson, Christine L; Johnson, Christopher H; Hoots, Brooke; Shouse, Roy L

    2016-12-01

    To examine trends in racial/ethnic disparities in antiretroviral therapy (ART) prescription and viral suppression among HIV-infected persons in care, overall and among men who have sex with men (MSM), from 2009 to 2013. The Medical Monitoring Project (MMP) is a complex sample survey of HIV-infected adults receiving medical care in the United States. We used weighted interview and medical record data collected June 2009-May 2014 to estimate the prevalence of ART prescription and viral suppression among racial/ethnic groups overall and among MSM. We found significant increases in ART prescription and viral suppression among all racial/ethnic groups from 2009 to 2013, both overall and among MSM. By 2013, overall and among MSM, the Hispanic-white disparity in ART prescription was nonexistent, and the black-white disparity was not significant after accounting for differences between blacks and whites in age and length of HIV diagnosis. Despite reductions in racial/ethnic disparities in viral suppression over the time period, significant disparities remained among the total population, even after adjusting for differences in racial/ethnic group characteristics. Encouragingly, however, there was no significant Hispanic-white disparity in viral suppression among MSM by 2013. Despite significant improvements in ART prescription and viral suppression in recent years, racial and ethnic disparities persist, particularly for black persons. If the United States is to achieve the National HIV/AIDS Strategy goal of reducing HIV-related health disparities, continued efforts to accelerate the rate of improvement in ART prescription and viral suppression among Hispanic and black persons may need to be prioritized.

  14. Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression Among PLWHA with Panic Symptoms.

    Science.gov (United States)

    Sam, Tanyka Suzanne; Hutton, Heidi E; Lau, Bryan; McCaul, Mary E; Keruly, Jeanne; Moore, Richard; Chander, Geetanjali

    2015-11-01

    Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and antiretroviral therapy (ART) use, medication adherence, and viral suppression. Data were analyzed using generalized estimating equations and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9 % (n = 118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed.

  15. Sustainable HIV treatment in Africa through viral-load-informed differentiated care

    DEFF Research Database (Denmark)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara

    2015-01-01

    every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load...... to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay...... in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost...

  16. Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

    Directory of Open Access Journals (Sweden)

    Siliciano Robert F

    2011-08-01

    Full Text Available Abstract Elite suppressors or controllers (ES are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he developed proliferative, de novo CTL responses that suppressed replication of each of these variants. These responses, in combination with low viral fitness of each variant, may contribute to sustained elite control in this ES.

  17. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  18. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption

    Science.gov (United States)

    Scheid, Johannes F.; Horwitz, Joshua A.; Bar-On, Yotam; Kreider, Edward F.; Lu, Ching-Lan; Lorenzi, Julio C. C.; Feldmann, Anna; Braunschweig, Malte; Nogueira, Lilian; Oliveira, Thiago; Shimeliovich, Irina; Patel, Roshni; Burke, Leah; Cohen, Yehuda Z.; Hadrigan, Sonya; Settler, Allison; Witmer-Pack, Maggi; West, Anthony P.; Juelg, Boris; Keler, Tibor; Hawthorne, Thomas; Zingman, Barry; Gulick, Roy M.; Pfeifer, Nico; Learn, Gerald H.; Seaman, Michael S.; Bjorkman, Pamela J.; Klein, Florian; Schlesinger, Sarah J.; Walker, Bruce D.; Hahn, Beatrice H.; Nussenzweig, Michel C.; Caskey, Marina

    2016-01-01

    Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env1, in the setting of analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg kg−1 infusions of 3BNC117, separated by 3 or 2 weeks, respectively, are generally well tolerated. Infusions are associated with a delay in viral rebound for 5–9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals, emerging viruses show increased resistance, indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml−1, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9–19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans. PMID:27338952

  19. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies...... to increasing the provision of adherence counselling....

  20. Someone to count on: social support as an effect modifier of viral load suppression in a prospective cohort study.

    Science.gov (United States)

    Friedman, M Reuel; Coulter, Robert W S; Silvestre, Anthony J; Stall, Ron; Teplin, Linda; Shoptaw, Steve; Surkan, Pamela J; Plankey, Michael W

    2017-04-01

    Though functional social support has been shown to serve as a protective factor for HIV viral load suppression in other populations, scant research has examined this relationship among men who have sex with men (MSM) in the United States. We assessed characteristics of social support, effects of social support on HIV viral load, and moderation by social support of the relationship between psychosocial indicators of a synergistic epidemic (syndemic) and HIV viral load. We analyzed longitudinal data from HIV-positive MSM using antiretroviral therapy who were enrolled in the Multicenter AIDS Cohort Study between 2002 and 2009 (n = 712). First, we conducted reliability assessments of a one-item social support measure. Then, we conducted a series of generalized longitudinal mixed models to assess our research questions. Moderation was assessed using an interaction term. A three-level (low/medium/high) social support variable demonstrated high reliability (intraclass correlation coefficients  = 0.72; 95% CI: 0.70, 0.75). Black and Hispanic MSM reported lower social support than their White counterparts (p social support (p social support (p social support levels were associated with greater viral load suppression and lower viral load means (p Social support moderated the relationships between syndemic and HIV viral load (p social support. Creating strengths-based interventions may also have particularly high impact among HIV-positive MSM with the highest psychosocial burdens.

  1. HIV care visits and time to viral suppression, 19 U.S. jurisdictions, and implications for treatment, prevention and the national HIV/AIDS strategy.

    Directory of Open Access Journals (Sweden)

    H Irene Hall

    Full Text Available OBJECTIVE: Early and regular care and treatment for human immunodeficiency virus (HIV infection are associated with viral suppression, reductions in transmission risk and improved health outcomes for persons with HIV. We determined, on a population level, the association of care visits with time from HIV diagnosis to viral suppression. METHODS: Using data from 19 areas reporting HIV-related tests to national HIV surveillance, we determined time from diagnosis to viral suppression among 17,028 persons diagnosed with HIV during 2009, followed through December 2011, using data reported through December 2012. Using Cox proportional hazards models, we assessed factors associated with viral suppression, including linkage to care within 3 months of diagnosis, a goal set forth by the National HIV/AIDS Strategy, and number of HIV care visits as determined by CD4 and viral load test results, while controlling for demographic, clinical, and risk characteristics. RESULTS: Of 17,028 persons diagnosed with HIV during 2009 in the 19 areas, 76.6% were linked to care within 3 months of diagnosis and 57.0% had a suppressed viral load during the observation period. Median time from diagnosis to viral suppression was 19 months overall, and 8 months among persons with an initial CD4 count ≤ 350 cells/µL. During the first 12 months after diagnosis, persons linked to care within 3 months experienced shorter times to viral suppression (higher rate of viral suppression per unit time, hazard ratio [HR] = 4.84 versus not linked within 3 months; 95% confidence interval [CI] 4.27, 5.48. Persons with a higher number of time-updated care visits also experienced a shorter time to viral suppression (HR = 1.51 per additional visit, 95% CI 1.49, 1.52. CONCLUSIONS: Timely linkage to care and greater frequency of care visits were associated with faster time to viral suppression with implications for individual health outcomes and for secondary prevention.

  2. Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep

    Directory of Open Access Journals (Sweden)

    Burny Arsène

    2007-07-01

    Full Text Available Abstract Background During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts. Results In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303 replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303 had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset. Conclusion Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression

  3. Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... suppression by neuropeptide Y in the hippocampus is predominantly mediated by Y2 receptors, which, together with neuropeptide Y, are upregulated after seizures as a compensatory mechanism. To explore whether such upregulation could prevent seizures, we overexpressed Y2 receptors in the hippocampus using...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...

  4. Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression

    Directory of Open Access Journals (Sweden)

    Peter F Rebeiro

    2016-04-01

    Full Text Available Introduction: We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART use and viral suppression (VS. Methods: Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results: Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each. Female sex (risk ratio (RR=0.97 vs. males and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96 significantly decreased the probability of cART compared with heterosexual transmission. Conclusions: HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings.

  5. Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression

    Science.gov (United States)

    Rebeiro, Peter F; Cesar, Carina; Shepherd, Bryan E; De Boni, Raquel B; Cortés, Claudia P; Rodriguez, Fernanda; Belaunzarán-Zamudio, Pablo; Pape, Jean W; Padgett, Denis; Hoces, Daniel; McGowan, Catherine C; Cahn, Pedro

    2016-01-01

    Introduction We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission. Conclusions HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings. PMID:27065108

  6. HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

    Science.gov (United States)

    Strehlau, R; Kuhn, L; Abrams, E J; Coovadia, A

    2016-11-01

    HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes. © 2016 John Wiley & Sons Ltd.

  7. Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on Antiretroviral Therapy (ART in sub-Saharan Africa: Frequency and clinical significance

    Directory of Open Access Journals (Sweden)

    Kamya Moses R

    2008-10-01

    Full Text Available Abstract Background A proportion of individuals who start antiretroviral therapy (ART fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4 in an urban HIV research cohort in Kampala, Uganda Methods We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04–04/05. We described the patterns of SO-CD4 both in terms of:- I magnitude of CD4 cell increase (a CD4 count increase Results Of 559 patients initiating ART, 386 (69% were female. Median (IQR age and baseline CD4 counts were 38 yrs (33–44 and 98 cells/μl (21–163 respectively; 414 (74% started a d4T-based regimen (D4T+3TC+NVP and 145 (26% a ZDV-based regimen (ZDV+3TC+EFV. After 6, 12 and 24 months of ART, 380 (68%, 339 (61% and 309 (55% had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%, 151 (45% and 166 (54% respectively had SO-CD4 based on criteria I, and 165(43%, 143(42% and 58(19% respectively based on criteria II. With both criteria combined, 56 (15% and 129 (38% had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58% of those that had SO-CD4 at 6 months (using criteria I maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12–29] and without SO-CD4 [23/100PYO (19–28]. Conclusion Using criteria I, the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T-cell functional recovery among patients with SO-CD4.

  8. Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

    DEFF Research Database (Denmark)

    Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga

    2014-01-01

    BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years...... of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing...... age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3...

  9. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Directory of Open Access Journals (Sweden)

    Cameron R Cunningham

    2016-01-01

    Full Text Available Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.

  10. Sustained happiness? Lack of repetition suppression in right-ventral visual cortex for happy faces.

    Science.gov (United States)

    Suzuki, Atsunobu; Goh, Joshua O S; Hebrank, Andrew; Sutton, Bradley P; Jenkins, Lucas; Flicker, Blair A; Park, Denise C

    2011-09-01

    Emotional stimuli have been shown to preferentially engage initial attention but their sustained effects on neural processing remain largely unknown. The present study evaluated whether emotional faces engage sustained neural processing by examining the attenuation of neural repetition suppression to repeated emotional faces. Repetition suppression of neural function refers to the general reduction of neural activity when processing a repeated stimulus. Preferential processing of emotional face stimuli, however, should elicit sustained neural processing such that repetition suppression to repeated emotional faces is attenuated relative to faces with no emotional content. We measured the reduction of functional magnetic resonance imaging signals associated with immediate repetition of neutral, angry and happy faces. Whereas neutral faces elicited the greatest suppression in ventral visual cortex, followed by angry faces, repetition suppression was the most attenuated for happy faces. Indeed, happy faces showed almost no repetition suppression in part of the right-inferior occipital and fusiform gyri, which play an important role in face-identity processing. Our findings suggest that happy faces are associated with sustained visual encoding of face identity and thereby assist in the formation of more elaborate representations of the faces, congruent with findings in the behavioral literature.

  11. Low viral suppression and high HIV diagnosis rate among men who have sex with men with syphilis--Baltimore, Maryland.

    Science.gov (United States)

    Cooley, Laura A; Pearl, Marcia L; Flynn, Colin; Ross, Christine; Hart-Cooper, Geoffrey; Elmore, Kim; Blythe, David; Morgan, James; Oster, Alexandra M

    2015-04-01

    The burden of syphilis and HIV among gay, bisexual, and other men who have sex with men (MSM) in Baltimore, Maryland, is substantial. Syphilis and HIV surveillance data were analyzed to characterize MSM with syphilis, including those with repeat infection and HIV coinfection, to strengthen prevention efforts. MSM 15 years or older from Baltimore City or County diagnosed as having early syphilis in 2010 to 2011 were included. Those previously treated for syphilis in 2007 to 2011 were considered to have repeat syphilis infection. HIV surveillance data were used to identify HIV coinfection and assess viral suppression. For MSM not diagnosed as having HIV at or before their syphilis diagnosis, annual HIV diagnosis rates were estimated, using Baltimore City data. Of 460 MSM with early syphilis in 2010 or 2011, 92 (20%) had repeat infection; 55% of MSM with a single diagnosis and 86% with repeat infection were HIV coinfected. Among MSM diagnosed as having HIV, viral suppression was low (25%, or 46% of those with a viral load reported). Among Baltimore City MSM without a prior HIV diagnosis, estimated annual HIV diagnosis rates were high (5% for those with 1 syphilis diagnosis, 23% for those with repeat infection). Baltimore-area MSM with syphilis, particularly those with repeat infection, represent a unique population for whom coinfection with HIV is high. Increasing frequency of syphilis and HIV testing among Baltimore area MSM with a syphilis diagnosis and prioritizing HIV-infected MSM with syphilis in efforts to achieve viral suppression may improve outcomes locally for both infections.

  12. Pre-clinical carotid atherosclerosis and sCD163 among virally suppressed HIV patients in Botswana compared with uninfected controls

    OpenAIRE

    Mosepele, Mosepele; Hemphill, Linda C.; Moloi, Walter; Moyo, Sikhulile; Nkele, Isaac; Makhema, Joseph; Bennett, Kara,; Triant, Virginia A.; Lockman, Shahin

    2017-01-01

    Objectives Human immune deficiency virus (HIV) is associated with increased cardiovascular disease (CVD) risk, yet the relationship between HIV and carotid atherosclerosis / monocyte activation among virally suppressed HIV-infected patients in sub-Saharan Africa is not well understood. Methods We measured traditional CVD risk factors, bilateral distal common carotid intima media thickness (cIMT), presence of carotid plaque and plasma sCD163 levels among virally suppressed HIV-infected adults ...

  13. Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.

    Directory of Open Access Journals (Sweden)

    Ilker Kudret Sariyer

    Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to

  14. Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles.

    Science.gov (United States)

    Andresen, Vibeke; Pise-Masison, Cynthia A; Sinha-Datta, Uma; Bellon, Marcia; Valeri, Valerio; Washington Parks, Robyn; Cecchinato, Valentina; Fukumoto, Risaku; Nicot, Christophe; Franchini, Genoveffa

    2011-08-11

    Disease development in human T-cell leukemia virus type 1 (HTLV-1)-infected individuals is positively correlated with the level of integrated viral DNA in T cells. HTLV-1 replication is positively regulated by Tax and Rex and negatively regulated by the p30 and HBZ proteins. In the present study, we demonstrate that HTLV-1 encodes another negative regulator of virus expression, the p13 protein. Expressed separately, p13 localizes to the mitochondria, whereas in the presence of Tax, part of it is ubiquitinated, stabilized, and rerouted to the nuclear speckles. The p13 protein directly binds Tax, decreases Tax binding to the CBP/p300 transcriptional coactivator, and, by reducing Tax transcriptional activity, suppresses viral expression. Because Tax stabilizes its own repressor, these findings suggest that HTLV-1 has evolved a complex mechanism to control its own replication. Further, these results highlight the importance of studying the function of the HTLV-1 viral proteins, not only in isolation, but also in the context of full viral replication.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44...... HIV-1-positive individuals. The phenotypic and cytokine profiles, and also the specificity of the CD8(+) T cells, were correlated with the suppression of HIV-1 replication. We also aimed to determine whether antiretroviral therapy (ART) had any positive effect on the HIV-1 suppressive CD8(+) T cells....... METHOD: Ex vivo suppression assay was used to evaluate the ability of CD8(+) T cells to suppress HIV-1 replication in autologous CD4(+) T cells. The CD107a, interferon-γ, interleukin-2, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1β (MIP-1β) responses to HIV-1 were evaluated...

  16. Condomless Sex Among Virally Suppressed Women With HIV With Regular HIV-Serodiscordant Sexual Partners in the Era of Treatment as Prevention.

    Science.gov (United States)

    Patterson, Sophie; Carter, Allison; Nicholson, Valerie; Webster, Kath; Ding, Erin; Kestler, Mary; Ogilvie, Gina; de Pokomandy, Alexandra; Loutfy, Mona; Kaida, Angela

    2017-12-01

    Sexual HIV transmission does not occur with sustained undetectable viral load (VL) on antiretroviral therapy (ART). Awareness of ART prevention benefits and its influence on condom use among women with HIV (WWH) remain unexplored. We estimated prevalence and correlates of condomless sex with regular HIV-serodiscordant partners among WWH with undetectable VL on ART. We used baseline questionnaire data from the community-based longitudinal Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). We included WWH self-reporting vaginal/anal sex with ≥1 HIV-negative/unknown status regular partner within 6 months, and undetectable VL (sex was defined as sex. Of 271 participants (19% of the CHIWOS cohort), median age was 41 (interquartile range: 34-47), 51% were in a relationship, 55% reported condomless sex, and 75% were aware of ART prevention benefits. Among women aware, 63% reported condomless sex compared with 32% of women not aware (P sex included being aware of ART prevention benefits (adjusted odds ratio: 4.08; 95% confidence interval: 2.04 to 8.16), white ethnicity, ≥high-school education, residing in British Columbia, and being in a relationship. Virally suppressed women aware of ART prevention benefits had 4-fold greater odds of condomless sex. Advancing safer sex discussions beyond condoms is critical to support women in regular serodiscordant partnerships to realize options for safe and satisfying sexuality in the Treatment-as-Prevention era.

  17. Slow build-up of cochlear suppression during sustained contralateral noise: central modulation of olivocochlear efferents?

    Science.gov (United States)

    Larsen, Erik; Liberman, M. Charles

    2009-01-01

    The strength of the medial olivocochlear (OC) reflex is routinely assayed by measuring suppression of ipsilateral responses such as otoacoustic emissions (OAEs) by a brief contralateral noise, e.g. (Berlin et al., 1995). Here, we show in anesthetized guinea pigs, that the magnitude of OC-mediated suppression of ipsilateral cochlear responses (i.e. compound actions potentials (CAPs), distortion product (DP) OAEs and round-window noise) slowly builds over 2–3 minutes during a sustained contralateral noise. The magnitude of this build-up suppression was largest at low ipsilateral stimulus intensities, as seen for suppression measured at contra-noise onset. However, as a function of stimulus frequency, build-up suppression magnitude was complementary to onset suppression, i.e. largest at the lowest and highest frequencies tested. Both build-up and onset suppression were eliminated by cutting the OC bundle. In contrast to “slow effects” of shock-evoked medial OC activity (Sridhar et al., 1995), which are mediated by slow intracellular changes in Ca concentration in OHCs, build-up effects of contralateral noise are immediately extinguished upon OC bundle transection and are likely mediated by central modulation of the response rates in MOC fibers due to the sustained noise. Results suggest that conventional tests of OC reflex strength may underestimate its magnitude in noisy environments. PMID:19232534

  18. CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV.

    Science.gov (United States)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Gitte; Pedersen, Court; Obel, Niels; Gerstoft, Jan

    2013-07-01

    The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer. Patients with human immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable. We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2-5.4]). CD4 counts dropped from a median of 492 cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate ratio, 11.7 [95% CI, 3.6-37.4] and 13.7 [95% CI, 4.3-43.6], respectively, and mortality rate ratio 4.3 [95% CI, 1.1-17.6]). A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer, and death among virally suppressed HIV patients.

  19. Low levels of viral suppression among refugees and host nationals accessing antiretroviral therapy in a Kenyan refugee camp.

    Science.gov (United States)

    Mendelsohn, Joshua B; Spiegel, Paul; Grant, Alison; Doraiswamy, Sathyanarayanan; Schilperoord, Marian; Larke, Natasha; Burton, John Wagacha; Okonji, Jully A; Zeh, Clement; Muhindo, Bosco; Mohammed, Ibrahim M; Mukui, Irene N; Patterson, Njogu; Sondorp, Egbert; Ross, David A

    2017-01-01

    Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011-2013) were compared on outcome measures that included viral suppression and adherence to ART. This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load refugees and 84% (86/102) of Kenyan host nationals participated in the Round One survey; 60% (44/73) and 58% (50/86) of Round One participants were recruited for Round Two follow-up viral load testing. In Round One, refugees were older than host nationals (median age 36 years, interquartile range, IQR 31, 41 vs 32 years, IQR 27, 38); the groups had similar time on ART (median 147 weeks, IQR 38, 64 vs 139 weeks, IQR 39, 225). There was weak evidence for a difference between proportions of refugees and host nationals who were virologically suppressed (Refugee status was not associated with viral suppression in multivariable analysis (adjusted odds ratio: 1.69, 95% CI 0.79, 3.57; p = 0.17). Among those not suppressed at either timepoint, 69% (9/13) exhibited resistance mutations. Virologic outcomes among refugees and host nationals were similar but unacceptably low. Slight improvements were observed after a remedial intervention. Virologic monitoring was important for identifying an underperforming ART program in a remote facility that serves refugees alongside host nationals. This work highlights the importance of careful laboratory monitoring of vulnerable populations accessing ART in remote settings.

  20. High-level HIV-1 viremia suppresses viral antigen-specific CD4+ T cell proliferation

    OpenAIRE

    McNeil, Andrew C.; Shupert, W. Lesley; Iyasere, Christiana A.; Hallahan, Claire W.; Mican, JoAnn; Davey, Richard T.; Connors, Mark

    2001-01-01

    In chronic viral infections of humans and experimental animals, virus-specific CD4+ T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4+ T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4+ T cells are killed upon encountering the virus, and maintenance of CD4+ T cell responses in some patien...

  1. Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome

    Directory of Open Access Journals (Sweden)

    Mohammed Ahmed

    2009-06-01

    Full Text Available Abstract Outbreaks of Dengue impose a heavy economic burden on developing countries in terms of vector control and human morbidity. Effective vaccines against all four serotypes of Dengue are in development, but population replacement with transgenic vectors unable to transmit the virus might ultimately prove to be an effective approach to disease suppression, or even eradication. A key element of the refractory transgenic vector approach is the development of transgenes that effectively prohibit viral transmission. In this report we test the effectiveness of several hammerhead ribozymes for suppressing DENV in lentivirus-transduced mosquito cells in an attempt to mimic the transgenic use of these effector molecules in mosquitoes. A lentivirus vector that expresses these ribozymes as a fusion RNA molecule using an Ae. aegypti tRNAval promoter and terminating with a 60A tail insures optimal expression, localization, and activity of the hammerhead ribozyme against the DENV genome. Among the 14 hammerhead ribozymes we designed to attack the DENV-2 NGC genome, several appear to be relatively effective in reducing virus production from transduced cells by as much as 2 logs. Among the sequences targeted are 10 that are conserved among all DENV serotype 2 strains. Our results confirm that hammerhead ribozymes can be effective in suppressing DENV in a transgenic approach, and provide an alternative or supplementary approach to proposed siRNA strategies for DENV suppression in transgenic mosquitoes.

  2. For Many Served By The Ryan White HIV/AIDS Program, Disparities In Viral Suppression Decreased, 2010-14.

    Science.gov (United States)

    Doshi, Rupali K; Milberg, John; Jumento, Theresa; Matthews, Tracy; Dempsey, Antigone; Cheever, Laura W

    2017-01-01

    For twenty-five years, the Ryan White HIV/AIDS Program has supported a comprehensive system of health services for vulnerable and under- or uninsured people living with HIV. Using data from the Health Resources and Services Administration about people living with HIV and served by the Ryan White HIV/AIDS Program, we found reductions in disparities in viral suppression rates between 2010 and 2014-with rates for Blacks/African Americans, adolescents and young adults, and people living in the South becoming more similar to rates for Whites, older adults, and people in other regions of the United States, respectively. Although absolute viral suppression rates for people without stable housing and transgender people improved during the same time period, disparities were not reduced between these groups and those with stable housing and nontransgender people, respectively. Addressing persistent disparities through the effective use of this program will be one of the key ways to meet the goals of the National HIV/AIDS Strategy. Project HOPE—The People-to-People Health Foundation, Inc.

  3. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

    Science.gov (United States)

    Kahana, Shoshana Y; Jenkins, Richard A; Bruce, Douglas; Fernandez, Maria I; Hightow-Weidman, Lisa B; Bauermeister, Jose A

    2016-01-01

    The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States. The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability). Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

  4. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

    Directory of Open Access Journals (Sweden)

    Shoshana Y Kahana

    Full Text Available The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural and Esri Crime (e.g., global crime index databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1 being on antiretroviral therapy (ART currently; (2 being on ART for at least 6 months; (3 missed HIV care appointments (not having missed any vs. having missed one or more appointments over the past 12 months; and (4 viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability.Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%; ART use for ≥6 months (n = 861, 45.53%; at least one missed HIV care appointment (n = 936, 49.50; and viral suppression (n = 577, 30.51%. After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

  5. Treatment as prevention in resource-limited settings: is it feasible to maintain HIV viral load suppression over time?

    Science.gov (United States)

    Socías, María Eugenia; Rotryng, Flavio; Lapadula, Pablo; Medrano, Maira; Paz, Daniela; Stern, Liliana; Lambierto, Alberto; Pryluka, Daniel

    2013-08-15

    Recently, there has been increasing interest in the role of "treatment as prevention" (TasP). Some of the questions regarding TasP strategies arise from the perceived difficulties in achieving and maintaining viral load (VL) suppression over time and the risk of emergence of viral resistance that could compromise future treatment options. This study was conducted to assess these questions in a resource-limited setting. We performed a retrospective observational study of HIV-infected patients diagnosed in the pre-HAART era on follow-up at a private center from Buenos Aires, Argentina. Socio-demographic, clinical, and laboratory data were extracted from clinical charts. Analyses were performed to test for potential associations of selected variables with current virologic failure or use of third-line drugs. Of 619 patients on follow-up, 82 (13.2%) were diagnosed in the pre-HAART era. At the time of our study, 79 (96.3%) patients were on HAART, with a median duration of 14 years (IQR 12-15) of therapy, and exposure to mono or dual nucleoside reverse transcriptase inhibitors regimens in 47.8% of cases. Sixty-nine patients (87.3%) had undetectable VL, 37 (46.8%) never presented virologic failure, and 19 (24.1%) experienced only one failure. Thirteen patients (16.5%) were receiving third-line ART regimens, with an average of 2.7-fold more virologic failures than those on first- or second-line regimens (p = 0.007). Maintaining viral load suppression over time in resource-limited-settings is feasible.

  6. Slow build-up of cochlear suppression during sustained contralateral noise: central modulation of olivocochlear efferents?

    Science.gov (United States)

    Larsen, Erik; Liberman, M Charles

    2009-10-01

    The strength of the medial olivocochlear (OC) reflex is routinely assayed by measuring suppression of ipsilateral responses such as otoacoustic emissions (OAEs) by a brief contralateral noise, e.g., (Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., Szabo, P. 1993. Does type I afferent dysfunction reveal itself through lack of efferent suppression. Hear. Res. 65, 40-50). Here, we show in anesthetized guinea pigs, that the magnitude of OC-mediated suppression of ipsilateral cochlear responses (i.e., compound actions potentials (CAPs), distortion product (DP) OAEs and round-window noise) slowly builds over 2-3 min during a sustained contralateral noise. The magnitude of this build-up suppression was largest at low ipsilateral stimulus intensities, as seen for suppression measured at contra-noise onset. However, as a function of stimulus frequency, build-up suppression magnitude was complementary to onset suppression, i.e., largest at the lowest and highest frequencies tested. Both build-up and onset suppression were eliminated by cutting the OC bundle. In contrast to "slow effects" of shock-evoked medial OC activity (Sridhar, T.S., Liberman, M.C., Brown, M.C., Sewell, W.F. 1995. A novel cholinergic "slow effect" of efferent stimulation on cochlear potentials in the guinea pig. J. Neurosci. 15, 3667-3678), which are mediated by slow intracellular changes in Ca concentration in OHCs, build-up effects of contralateral noise are immediately extinguished upon OC bundle transection and are likely mediated by central modulation of the response rates in MOC fibers due to the sustained noise. Results suggest that conventional tests of OC reflex strength may underestimate its magnitude in noisy environments. 2009 Elsevier B.V.

  7. Comparative analysis of RNA silencing suppression activities between viral suppressors and an endogenous plant RNA-dependent RNA polymerase.

    Science.gov (United States)

    Yoon, Ju-Yeon; Han, Kyoung-Sik; Park, Han-Yong; Choi, Seung-Kook

    2012-06-01

    RNA silencing is an evolutionarily conserved system that functions as an antiviral mechanism in eukaryotes, including higher plants. To counteract this, several plant viruses express silencing suppressors that inhibit RNA silencing in host plants. Here, we show that both 2b protein from peanut stunt virus (PSV) and a hairpin construct (designated hp-RDR6) that silences endogenous RNA-dependent RNA polymerase 6 (RDR6) strongly suppress RNA silencing. The Agrobacterium infiltration system was used to demonstrate that both PSV 2b and hp-RDR6 suppressed local RNA silencing as strongly as helper component (HC-Pro) from potato virus Y (PVY) and P19 from tomato bush stunt virus (TBSV). The 2b protein from PSV eliminated the small-interfering RNAs (siRNAs) associated with RNA silencing and prevented systemic silencing, similar to 2b protein from cucumber mosaic virus (CMV). On the other hand, hp-RDR6 suppressed RNA silencing by inhibiting the generation of secondary siRNAs. The small coat protein (SCP) of squash mosaic virus (SqMV) also displayed weak suppression activity of RNA silencing. Agrobacterium-mediated gene transfer was used to investigate whether viral silencing suppressors or hp-RDR6 enhanced accumulations of green fluorescence protein (GFP) and β-glucuronidase (GUS) as markers of expression in leaf tissues of Nicotina benthamiana. Expression of both GFP and GUS was significantly enhanced in the presence of PSV 2b or CMV 2b, compared to no suppression or the weak SqMV SCP suppressor. Co-expression with hp-RDR6 also significantly increased the expression of GFP and GUS to levels similar to those induced by PVY HC-Pro and TBSV P19.

  8. Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer

    Science.gov (United States)

    Paiva, Leticia R.; Silva, Hallan S.; Ferreira, Silvio C.; Martins, Marcelo L.

    2013-04-01

    Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8+ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.

  9. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

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

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    Edward Seung

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

  11. CD4 Decline Is Associated With Increased Risk of Cardiovascular Disease, Cancer, and Death in Virally Suppressed Patients With HIV

    DEFF Research Database (Denmark)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten Schade

    2013-01-01

    cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate......Background. The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer. Methods. Patients with human...... immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline...

  12. Waves of visibility: probing the depth of inter-ocular suppression with transient and sustained targets

    Directory of Open Access Journals (Sweden)

    Lisandro eKaunitz

    2014-07-01

    Full Text Available In order to study non-conscious visual processing, researchers render otherwise consciously perceived images into invisible stimuli. Through the years, several psychophysical techniques have been developed for this purpose. Yet the comparison of experimental results across techniques remains a difficult task as the depth of suppression depends on the interactions between the type of stimuli and the suppression methods employed. This poses a limit to the inferences that researchers make about the extent of non-conscious processes. We investigated the mechanisms underlying inter-ocular suppression during continuous flash suppression (CFS and dichoptic visual masking using a transient onset target stimulus and a variety of stimulus / mask temporal manipulations. We show that target duration, timing of target onset, and mask frequency are key aspects of inter-ocular suppression during CFS with transient targets. The differences between our results and sustained target CFS studies suggest that two distinct mechanisms are involved in the detection of transient and prolonged target stimuli during CFS. Our results provide insight into the dynamics of CFS together with evidence for similarities between transient target CFS and dichoptic visual masking.

  13. Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors

    Science.gov (United States)

    Lakatos, Lóránt; Csorba, Tibor; Pantaleo, Vitantonio; Chapman, Elisabeth J; Carrington, James C; Liu, Yu-Ping; Dolja, Valerian V; Calvino, Lourdes Fernández; López-Moya, Juan José; Burgyán, József

    2006-01-01

    RNA silencing is an evolutionarily conserved system that functions as an antiviral mechanism in higher plants and insects. To counteract RNA silencing, viruses express silencing suppressors that interfere with both siRNA- and microRNA-guided silencing pathways. We used comparative in vitro and in vivo approaches to analyse the molecular mechanism of suppression by three well-studied silencing suppressors. We found that silencing suppressors p19, p21 and HC-Pro each inhibit the intermediate step of RNA silencing via binding to siRNAs, although the molecular features required for duplex siRNA binding differ among the three proteins. None of the suppressors affected the activity of preassembled RISC complexes. In contrast, each suppressor uniformly inhibited the siRNA-initiated RISC assembly pathway by preventing RNA silencing initiator complex formation. PMID:16724105

  14. Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity.

    Directory of Open Access Journals (Sweden)

    Marianne Lucas-Hourani

    Full Text Available Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response.

  15. Retention in care, viral suppression, treatment adherence and quality of life in a public antiretroviral therapy program in Addis Ababa, Ethiopia

    NARCIS (Netherlands)

    Mekuria, L.A.

    2016-01-01

    In his thesis, Legese A. Mekuria presents the results of a PhD study which was undertaken in 10 health-care facilities in Addis Ababa, Ethiopia. The overall aim was to estimate retention in HIV care, viral suppression, medication adherence and patients’ health-related quality of life (HRQoL). An

  16. Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort.

    Science.gov (United States)

    Tanner, Zachary; Lachowsky, Nathan; Ding, Erin; Samji, Hasina; Hull, Mark; Cescon, Angela; Patterson, Sophie; Chia, Jason; Leslie, Alia; Raboud, Janet; Loutfy, Mona; Cooper, Curtis; Klein, Marina; Machouf, Nima; Tsoukas, Christos; Montaner, Julio; Hogg, Robert S

    2016-10-21

    Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada's three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures 200 copies/mL ≥30 days apart). Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1-Q3: 3-7 months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.

  17. Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort

    Directory of Open Access Journals (Sweden)

    Zachary Tanner

    2016-10-01

    Full Text Available Abstract Background Gay, bisexual and other men who have sex with men (MSM are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. Methods Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada’s three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures 200 copies/mL ≥30 days apart. Results Of 2,858 participants, 2,448 (86 % achieved viral suppression in a median time of 5 months (Q1–Q3: 3–7 months. Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 % experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. Conclusions Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.

  18. Type I Interferon Induced Epigenetic Regulation of Macrophages Suppresses Innate and Adaptive Immunity in Acute Respiratory Viral Infection.

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    Danielle N Kroetz

    2015-12-01

    Full Text Available Influenza A virus (IAV is an airborne pathogen that causes significant morbidity and mortality each year. Macrophages (Mϕ are the first immune population to encounter IAV virions in the lungs and are required to control infection. In the present study, we explored the mechanism by which cytokine signaling regulates the phenotype and function of Mϕ via epigenetic modification of chromatin. We have found that type I interferon (IFN-I potently upregulates the lysine methyltransferase Setdb2 in murine and human Mϕ, and in turn Setdb2 regulates Mϕ-mediated immunity in response to IAV. The induction of Setdb2 by IFN-I was significantly impaired upon inhibition of the JAK-STAT signaling cascade, and chromatin immunoprecipitation revealed that both STAT1 and interferon regulatory factor 7 bind upstream of the transcription start site to induce expression. The generation of Setdb2LacZ reporter mice revealed that IAV infection results in systemic upregulation of Setdb2 in myeloid cells. In the lungs, alveolar Mϕ expressed the highest level of Setdb2, with greater than 70% lacZ positive on day 4 post-infection. Silencing Setdb2 activity in Mϕ in vivo enhanced survival in lethal IAV infection. Enhanced host protection correlated with an amplified antiviral response and less obstruction to the airways. By tri-methylating H3K9, Setdb2 silenced the transcription of Mx1 and Isg15, antiviral effectors that inhibit IAV replication. Accordingly, a reduced viral load in knockout mice on day 8 post-infection was linked to elevated Isg15 and Mx1 transcript in the lungs. In addition, Setdb2 suppressed the expression of a large number of other genes with proinflammatory or immunomodulatory function. This included Ccl2, a chemokine that signals through CCR2 to regulate monocyte recruitment to infectious sites. Consistently, knockout mice produced more CCL2 upon IAV infection and this correlated with a 2-fold increase in the number of inflammatory monocytes and

  19. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

    Science.gov (United States)

    Baroncelli, Silvia; Pirillo, Maria F; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-07-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

  20. Predictors of linkage to HIV care and viral suppression after release from jails and prisons: a retrospective cohort study.

    Science.gov (United States)

    Loeliger, Kelsey B; Altice, Frederick L; Desai, Mayur M; Ciarleglio, Maria M; Gallagher, Colleen; Meyer, Jaimie P

    2017-11-27

    Incarceration provides an opportunity for engagement in HIV care but is associated with poor HIV treatment outcomes after release. We aimed to assess post-release linkage to HIV care (LTC) and the effect of transitional case management services. To create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut, USA (2007-14), we linked administrative custody and pharmacy databases with mandatory HIV/AIDS surveillance monitoring and case management data. We examined time to LTC (defined as first viral load measurement after release) and viral suppression at LTC. We used generalised estimating equations to show predictors of LTC within 14 days and 30 days of release. Among 3302 incarceration periods for 1350 individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14 days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301 (29%) of 1042 had detectable viral loads at LTC. Factors positively associated with LTC within 14 days of release are intermediate (31-364 days) incarceration duration (adjusted odds ratio 1·52; 95% CI 1·19-1·95), and transitional case management (1·65; 1·36-1·99), receipt of antiretroviral therapy during incarceration (1·39; 1·11-1·74), and two or more medical comorbidities (1·86; 1·48-2·36). Reincarceration (0·70; 0·56-0·88) and conditional release (0·62; 0·50-0·78) were negatively associated with LTC within 14 days. Hispanic ethnicity, bonded release, and psychiatric comorbidity were also associated with LTC within 30 days but reincarceration was not. LTC after release is suboptimal but improves when inmates' medical, psychiatric, and case management needs are identified and addressed before release. People who are rapidly cycling through jail facilities are particularly vulnerable to missed linkage opportunities. The use of integrated programmes to align justice and health-care goals has great potential to improve long-term HIV treatment outcomes. US

  1. Suppression of Jasmonic Acid-Mediated Defense by Viral-Inducible MicroRNA319 Facilitates Virus Infection in Rice.

    Science.gov (United States)

    Zhang, Chao; Ding, Zuomei; Wu, Kangcheng; Yang, Liang; Li, Yang; Yang, Zhen; Shi, Shan; Liu, Xiaojuan; Zhao, Shanshan; Yang, Zhirui; Wang, Yu; Zheng, Luping; Wei, Juan; Du, Zhenguo; Zhang, Aihong; Miao, Hongqin; Li, Yi; Wu, Zujian; Wu, Jianguo

    2016-09-06

    MicroRNAs (miRNAs) are pivotal modulators of plant development and host-virus interactions. However, the roles and action modes of specific miRNAs involved in viral infection and host susceptibility remain largely unclear. In this study, we show that Rice ragged stunt virus (RRSV) infection caused increased accumulation of miR319 but decreased expression of miR319-regulated TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) genes, especially TCP21, in rice plants. Transgenic rice plants overexpressing miR319 or downregulating TCP21 exhibited disease-like phenotypes and showed significantly higher susceptibility to RRSV in comparison with the wild-type plants. In contrast, only mild disease symptoms were observed in RRSV-infected lines overexpressing TCP21 and especially in the transgenic plants overexpressing miR319-resistant TCP21. Both RRSV infection and overexpression of miR319 caused the decreased endogenous jasmonic acid (JA) levels along with downregulated expression of JA biosynthesis and signaling-related genes in rice. However, treatment of rice plants with methyl jasmonate alleviated disease symptoms caused by RRSV and reduced virus accumulation. Taken together, our results suggest that the induction of miR319 by RRSV infection in rice suppresses JA-mediated defense to facilitate virus infection and symptom development. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  2. Doubly Spliced RNA of Hepatitis B Virus Suppresses Viral Transcription via TATA-Binding Protein and Induces Stress Granule Assembly.

    Science.gov (United States)

    Tsai, Kuen-Nan; Chong, Chin-Liew; Chou, Yu-Chi; Huang, Chien-Chiao; Wang, Yi-Ling; Wang, Shao-Win; Chen, Mong-Liang; Chen, Chun-Hong; Chang, Chungming

    2015-11-01

    genotypes. Using cultured human hepatoma cells as a model of HBV infection, we found that the expression of 2.2DS-RNA caused a decrease in HBV replication. In cultured cells, the ectopic expression of 2.2DS-RNA obviously reduced the intracellular levels of HBV mRNAs. Our analysis of the 2.2DS-RNA-mediated suppression of viral RNA expression showed that 2.2DS-RNA inhibited transcription via binding to the TATA-binding protein and stress granule proteins. Our findings suggest that the 2.2DS-RNA acts as a suppressive noncoding RNA that modulates HBV replication, which may in turn influence the development of chronic hepatitis B. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Patterns of HIV service use and HIV viral suppression among patients treated in an academic infectious diseases clinic in North Carolina.

    Science.gov (United States)

    Palma, Anton; Lounsbury, David W; Messer, Lynne; Quinlivan, Evelyn Byrd

    2015-04-01

    Irregular participation in HIV medical care hinders HIV RNA suppression and impacts health among people living with HIV. Cluster analysis of clinical data from 1,748 patients attending a large academic medical center yielded three HIV service usage patterns, namely: 'engaged in care', 'sporadic care', and 'frequent use'. Patients 'engaged in care' exhibited most consistent retention (on average, >88 % of each patient's observation years had ≥2 visits 90 days apart), annualized visit use (2.9 mean visits/year) and viral suppression (>73 % HIV RNA tests use (1.7 visits/year) and viral suppression (56 % use' (5.2 visits/year) had more inpatient and emergency visits. Female, out-of-state residence, low attendance during the first observation year and detectable first-observed HIV RNA were early predictors of subsequent service usage. Patients 'engaged in care' were more likely to have HIV RNA <400 than those receiving sporadic care. Results confirm earlier findings that under-utilization of services predicts poorer viral suppression and health outcomes and support recommendations for 2-3 visits/year.

  4. Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study.

    Science.gov (United States)

    McCreesh, Nicky; Andrianakis, Ioannis; Nsubuga, Rebecca N; Strong, Mark; Vernon, Ian; McKinley, Trevelyan J; Oakley, Jeremy E; Goldstein, Michael; Hayes, Richard; White, Richard G

    2017-08-09

    UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study. An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated. In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%). People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

  5. Viral RNA silencing suppression

    NARCIS (Netherlands)

    Hedil, Marcio; Kormelink, Richard

    2016-01-01

    The Bunyaviridae is a family of arboviruses including both plant-and vertebrate-infecting representatives. The Tospovirus genus accommodates plant-infecting bunyaviruses, which not only replicate in their plant host, but also in their insect thrips vector during persistent propagative

  6. Suppression of high-energy electrons generated in both disrupting and sustained MST tokamak plasmas

    Science.gov (United States)

    Pandya, M. D.; Chapman, B. E.; Munaretto, S.; Cornille, B. S.; McCollam, K. J.; Sovinec, C. R.; Dubois, A. M.; Almagri, A. F.; Goetz, J. A.

    2017-10-01

    High-energy electrons appearing during MST tokamak plasma disruptions are rapidly lost from the plasma due apparently to internal MHD activity. Work has just recently begun on generating and diagnosing disruptions in MST tokamak plasmas. Initial measurements show the characteristic drop in central temperature and density preceding a quench of the plasma current. This corresponds to a burst of dominantly n=1 MHD activity, which is accompanied by a short-lived burst of high-energy electrons. The short-lived nature of these electrons is suspected to be due to stochastic transport associated with the increased MHD. Earlier work shows that runaway electrons generated in low density, sustained plasmas are suppressed by a sufficiently large m=3 RMP in plasmas with q(a) MST's thick conducting shell. With an m=3 RMP, the degree of runaway suppression increases with RMP amplitude, while an m=1 RMP has little effect on the runaways. Nonlinear MHD modeling with NIMROD of these MST plasmas indicates increased stochasticity with an m=3 RMP, while no such increase in stochasticity is observed with an m=1 RMP. Work supported by US DOE.

  7. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.

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    Hideyuki Onami

    Full Text Available We established a sustained vasohibin-1 (a 42-kDa protein, delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]. The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE, and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device, and vasohibin-1 intravitreal direct injection (0.24 μM groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.

  8. Direct infection of dendritic cells during chronic viral infection suppresses antiviral T cell proliferation and induces IL-10 expression in CD4 T cells.

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    Carmen Baca Jones

    Full Text Available Elevated levels of systemic IL-10 have been associated with several chronic viral infections, including HCV, EBV, HCMV and LCMV. In the chronic LCMV infection model, both elevated IL-10 and enhanced infection of dendritic cells (DCs are important for viral persistence. This report highlights the relationship between enhanced viral tropism for DCs and the induction of IL-10 in CD4 T cells, which we identify as the most frequent IL-10-expressing cell type in chronic LCMV infection. Here we report that infected CD8αneg DCs express elevated IL-10, induce IL-10 expression in LCMV specific CD4 T cells, and suppress LCMV-specific T cell proliferation. DCs exposed in vivo to persistent LCMV retain the capacity to stimulate CD4 T cell proliferation but induce IL-10 production by both polyclonal and LCMV-specific CD4 T cells. Our study delineates the unique effects of direct infection versus viral exposure on DCs. Collectively these data point to enhanced infection of DCs as a key trigger of the IL-10 induction cascade resulting in maintenance of elevated IL-10 expression in CD4 T cells and inhibition of LCMV-specific CD4 and CD8 T cell proliferation.

  9. "It Makes You Feel Like Someone Cares" acceptability of a financial incentive intervention for HIV viral suppression in the HPTN 065 (TLC-Plus) study.

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    Greene, Elizabeth; Pack, Allison; Stanton, Jill; Shelus, Victoria; Tolley, Elizabeth E; Taylor, Jamilah; El Sadr, Wafaa M; Branson, Bernard M; Leider, Jason; Rakhmanina, Natella; Gamble, Theresa

    2017-01-01

    HPTN 065 (TLC-Plus) evaluated the feasibility and effectiveness of providing quarterly $70 gift card financial incentives to HIV-infected patients on antiretroviral therapy (ART) to encourage ART adherence and viral suppression, and represents the largest study to-date of a financial incentive intervention for HIV viral suppression. A post-trial qualitative substudy was undertaken to examine acceptability of the financial incentives among those receiving and implementing the intervention. Between July and October 2013, semi-structured interviews were conducted with 72 patients and 12 investigators from 14 sites; three focus groups were conducted with 12 staff from 10 sites. Qualitative data collection elicited experiences with and attitudes about the intervention, including philosophical viewpoints and implementation experiences. Transcripts were analyzed in NVivo 10. Memos and matrices were developed to explore themes from different participant group perspectives. Patients, investigators, and staff found the intervention highly acceptable, primarily due to the emotional benefits gained through giving or receiving the incentive. Feeling rewarded or cared for was a main value perceived by patients; this was closely tied to the financial benefit for some. Other factors influencing acceptability for all included perceived effectiveness and health-related benefits, philosophical concerns about the use of incentives for health behavior change, and implementation issues. The termination of the incentive at the end of the study was disappointing to participants and unexpected by some, but generally accepted. Positive experiences with the financial incentive intervention and strategies used to facilitate implementation led to high acceptability of the intervention, despite some reluctance in principle to the use of incentives. The findings of this analysis provide encouraging evidence in support of the acceptability of a large-scale financial incentive intervention for HIV

  10. Poor CD4 recovery and risk of subsequent progression to AIDS or death despite viral suppression in a South African cohort

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    Simbarashe Takuva

    2014-03-01

    Full Text Available Introduction: The prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear. Methods: This was a cohort study of HIV-positive adults initiating antiretroviral therapy (ART between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml by six months on treatment in South Africa. Immunological response at six months was defined as: (1 absolute CD4 reached (<200 vs. ≥200 cells/ml; (2 absolute CD4 reached (0–49, 50–200 and ≥200 cells/ml; and (3 CD4 increase from ART initiation (<0, 0–49, 50–199 and ≥200 cells/ml. We used Cox regression models to determine the relationship between each definition and both new AIDS-defining condition and death. Results: A total of 4129 patients were eligible for analysis; 212 (5.1% of those patients experienced a new AIDS-defining condition and 154 (3.7% died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥200 cells/ml; adjusted hazard ratio (aHR: 2.6; 95% CI: 1.2–2.1 and death (aHR: 2.8; 95% CI: 1.4–5.7. A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2–4.9 and smaller CD4 count gains (0–49 cells/ml; aHR: 2.0; 95% CI: 1.2–3.4 and 50–199 cells/ml; aHR: 1.5; 95% CI: 0.9–2.2 were also associated with greater risk of progression to AIDS compared to an increase of ≥200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98–1.95. Conclusions: Patients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub-group of patients need further

  11. High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya.

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    Kwarisiima, Dalsone; Kamya, Moses R; Owaraganise, Asiphas; Mwangwa, Florence; Byonanebye, Dathan M; Ayieko, James; Plenty, Albert; Black, Doug; Clark, Tamara D; Nzarubara, Bridget; Snyman, Katherine; Brown, Lillian; Bukusi, Elizabeth; Cohen, Craig R; Geng, Elvin H; Charlebois, Edwin D; Ruel, Theodore D; Petersen, Maya L; Havlir, Diane; Jain, Vivek

    2017-07-21

    The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/μL and children (two to fourteen years) with CD4 > 500/μL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events. Results Overall, 972 HIV-positive adults with CD4+ ≥ 350/μL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28-42), CD4+ 608/μL (IQR, 487-788/μL) and VL 6775 copies/mL (IQR, <500-37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to

  12. Filariae-Retrovirus Co-infection in Mice is Associated with Suppressed Virus-Specific IgG Immune Response and Higher Viral Loads.

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    Dietze, Kirsten Katrin; Dittmer, Ulf; Koudaimi, Daniel Karim; Schimmer, Simone; Reitz, Martina; Breloer, Minka; Hartmann, Wiebke

    2016-12-01

    Worldwide more than 2 billion people are infected with helminths, predominantly in developing countries. Co-infections with viruses such as human immunodeficiency virus (HIV) are common due to the geographical overlap of these pathogens. Helminth and viral infections induce antagonistic cytokine responses in their hosts. Helminths shift the immune system to a type 2-dominated immune response, while viral infections skew the cytokine response towards a type 1 immune response. Moreover, chronic helminth infections are often associated with a generalized suppression of the immune system leading to prolonged parasite survival, and also to a reduced defence against unrelated pathogens. To test whether helminths affect the outcome of a viral infection we set up a filarial/retrovirus co-infection model in C57BL/6 mice. Although Friend virus (FV) infection altered the L. sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection. However, reciprocal control of FV infection was clearly impaired by concurrent L. sigmodontis infection. Spleen weight as an indicator of pathology and viral loads in spleen, lymph nodes (LN) and bone marrow (BM) were increased in L. sigmodontis/FV-co-infected mice compared to only FV-infected mice. Numbers of FV-specific CD8+ T cells as well as cytokine production by CD4+ and CD8+ cells were alike in co-infected and FV-infected mice. Increased viral loads in co-infected mice were associated with reduced titres of neutralising FV-specific IgG2b and IgG2c antibodies. In summary our findings suggest that helminth infection interfered with the control of retroviral infection by dampening the virus-specific neutralising antibody response.

  13. HIV Care and Viral Suppression During the Last Year of Life: A Comparison of HIV-Infected Persons Who Died of HIV-Attributable Causes With Persons Who Died of Other Causes in 2012 in 13 US Jurisdictions.

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    Adih, William K; Hall, H Irene; Selik, Richard M; Guo, Xiuchan

    2017-01-24

    Little information is available about care before death among human immunodeficiency virus (HIV)-infected persons who die of HIV infection, compared with those who die of other causes. The objective of our study was to compare HIV care and outcome before death among persons with HIV who died of HIV-attributable versus other causes. We used National HIV Surveillance System data on CD4 T-lymphocyte counts and viral loads within 12 months before death in 2012, as well as on underlying cause of death. Deaths were classified as "HIV-attributable" if the reported underlying cause was HIV infection, an AIDS-defining disease, or immunodeficiency and as attributable to "other causes" if the cause was anything else. Persons were classified as "in continuous care" if they had ≥2 CD4 or viral load test results ≥3 months apart in those 12 months and as having "viral suppression" if their last viral load was HIV-attributable or other causes, respectively, 65.28% (2104/3223) and 30.88% (1041/3371) met AIDS criteria within 12 months before death, and 33.76% (1088/3223) and 50.96% (1718/3371) had viral suppression. The percentage of persons who received ≥2 tests ≥3 months apart did not differ by cause of death. Prevalence of viral suppression for persons who ever had AIDS was lower among those who died of HIV but did not differ by cause for those who never had AIDS. The lower prevalence of viral suppression among persons who died of HIV than among those who died of other causes implies a need to improve viral suppression strategies to reduce mortality due to HIV infection.

  14. Viral suppression in adolescents on antiretroviral treatment: review of the literature and critical appraisal of methodological challenges.

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    Ferrand, Rashida A; Briggs, Datonye; Ferguson, Jane; Penazzato, Martina; Armstrong, Alice; MacPherson, Peter; Ross, David A; Kranzer, Katharina

    2016-03-01

    Medication adherence is often suboptimal for adolescents with HIV, and establishing correct weight-based antiretroviral therapy dosing is difficult, contributing to virological failure. This review aimed to determine the proportion of adolescents achieving virological suppression after initiating ART. MEDLINE, EMBASE and Web of Science databases were searched. Studies published between January 2004 and September 2014 including ≥50 adolescents taking ART and reporting on the proportion of virological suppressed participants were included. From a total of 5316 potentially relevant citations, 20 studies were included. Only eight studies reported the proportion of adolescents that were virologically suppressed at a specified time point. The proportion of adolescents with virological suppression at 12 months ranged from 27 to 89%. Adolescent achievement of HIV virological suppression was highly variable. Improved reporting of virological outcomes from a wider range of settings is required to support efforts to improve HIV care and treatment for adolescents. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  15. Black–White and Country of Birth Disparities in Retention in HIV Care and Viral Suppression among Latinos with HIV in Florida, 2015

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    Diana M. Sheehan

    2017-01-01

    Full Text Available The study’s purpose was to identify HIV, Black–White race, and birth country disparities in retention in HIV care and HIV viral load (VL suppression among Latinos, in 2015. Florida’s surveillance data for Latinos diagnosed with HIV (2000–2014 were merged with American Community Survey data. Multi-level (random effects models were used to estimate adjusted odds ratios (aOR for non-retention in care and non-viral load suppression. Blacks and Whites experienced similar odds of non–retention in care. Racial differences in VL suppression disappeared after controlling for neighborhood factors. Compared to U.S.–born Latinos, those born in Mexico (retention aOR 2.00, 95% CI 1.70–2.36; VL 1.85, 95% CI 1.57–2.17 and Central America (retention aOR 1.33, 95% CI 1.16–1.53; VL 1.28, 95% CI 1.12–2.47 were at an increased risk after controlling for individual and neighborhood factors. Among Central Americans, those born in Guatemala (retention aOR 2.39, 95% CI 1.80–3.18; VL 2.20, 95% CI 1.66–2.92 and Honduras (retention aOR 1.39, 95% CI 1.13–1.72; VL 1.42, 95% CI 1.16–1.74 experienced the largest disparities, when compared to U.S.-born Latinos. Disparities in care and treatment exist within the Latino population. Cultural and other factors, unique to Latino Black-White racial and birth country subgroups, should be further studied and considered for intervention.

  16. bta-miR-29b attenuates apoptosis by directly targeting caspase-7 and NAIF1 and suppresses bovine viral diarrhea virus replication in MDBK cells.

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    Fu, Qiang; Shi, Huijun; Shi, Mengting; Meng, Luping; Zhang, Hui; Ren, Yan; Guo, Fei; Jia, Bin; Wang, Pengyan; Ni, Wei; Chen, Chuangfu

    2014-07-01

    MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that serve as powerful regulators of multiple cellular processes, including apoptosis, differentiation, growth, and proliferation. Bovine viral diarrhea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industries. Although BVDV-induced apoptosis correlates with increased intracellular viral RNA accumulation and with bta-miR-29b (miR-29b) expression upregulation in Madin-Darby bovine kidney (MDBK) cells infected with BVDV strain NADL, the role of miR-29b in regulating BVDV-infection-related apoptosis remains unexplored. Here, we report that miR-29b serves as a new miRNA regulating apoptosis. We showed that miR-29b target sequences were present in the 3' untranslated regions of 2 key apoptosis regulators mRNAs, cysteine aspartases-7 (caspase-7) and nuclear apoptosis-inducing factor 1 (NAIF1). Indeed, upon miRNA overexpression, both mRNA and protein levels of caspase-7 and NAIF1 were decreased. We further found that miR-29b attenuated apoptosis by directly regulating intracellular levels of caspase-7 and NAIF1. Moreover, apoptosis blockage by miR-29b was rescued upon co-infection of MDBK cells with lentiviruses expressing caspase-7 and NAIF1. Importantly, miR-29b decreased BVDV NADL envelope glycoprotein E1 mRNA levels and suppressed viral replication. These studies advance our understanding of the mechanisms of miRNAs in mediating the cells combating viral infections.

  17. In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine.

    Science.gov (United States)

    Ma, Jian; Jiang, Chenggang; Lin, Yuezhi; Wang, Xuefeng; Zhao, Liping; Xiang, Wenhua; Shao, Yiming; Shen, Rongxian; Kong, Xiangang; Zhou, Jianhua

    2009-01-01

    To study the in vivo evolution of the attenuated Chinese equine infectious anemia virus (EIAV) vaccine, viral gp90 gene variation and virus replication in immunosuppressed hosts were investigated. The results showed that after vaccination, the gp90 gene followed an evolutionary trend of declining diversity. The trend coincided with the maturation of immunity to EIAV, and eventually, the gp90 gene became highly homologous. The sequences of these predominant quasispecies were consistently detected up to 18 months after vaccination. Furthermore, after transient immune suppression with dexamethasone, the plasma viral RNA copy number of the vaccine strain in three vaccinated ponies remained consistently below the "pathogenic threshold" level, while the viral load increased by 25,000-fold in the positive control of an inapparent carrier of the parental virulent strain. This study is the first to provide evidence for the safety of an attenuated lentiviral vaccine with decreased genomic diversity and consistently low viral replication under suppressed immunity.

  18. Pre-clinical carotid atherosclerosis and sCD163 among virally suppressed HIV patients in Botswana compared with uninfected controls.

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    Mosepele, Mosepele; Hemphill, Linda C; Moloi, Walter; Moyo, Sikhulile; Nkele, Isaac; Makhema, Joseph; Bennett, Kara; Triant, Virginia A; Lockman, Shahin

    2017-01-01

    Human immune deficiency virus (HIV) is associated with increased cardiovascular disease (CVD) risk, yet the relationship between HIV and carotid atherosclerosis / monocyte activation among virally suppressed HIV-infected patients in sub-Saharan Africa is not well understood. We measured traditional CVD risk factors, bilateral distal common carotid intima media thickness (cIMT), presence of carotid plaque and plasma sCD163 levels among virally suppressed HIV-infected adults and HIV-uninfected controls, in a cross-sectional study in Gaborone, Botswana. The associations between HIV status, traditional CVD risk factors, sCD163 and outcome of cIMT were assessed in univariate and multivariate linear regression models. We enrolled 208 HIV-infected adults (55% Female, mean age 39 years) who had undetectable HIV-1 RNA on antiretroviral therapy and 224 HIV-uninfected controls (47% Female, mean age 37 years). There was no difference in cIMT between study groups, with mean cIMT 0.607mm and 0.599mm in HIV-infected and HIV-uninfected, respectively (p = 0.37). Plasma sCD163 was significantly higher in HIV-infected versus HIV-uninfected persons (1917ng/ml vs 1593ng/ml, p = 0.003), but was not associated with cIMT (p = 0.43 among all, p = 0.72 for HIV-infected only). In the final multivariate model, increased cIMT was associated with older age, being treated for hypertension, and higher non-HDL cholesterol among all (polder age and waist-hip ratio in HIV-infected participants (p = 0.02 & p = 0.02 respectively). Carotid plaque was present in a significantly higher proportion of HIV-infected adults (RR 2.15, 95% CI 1.22, 3.81). HIV-infected participants aged 30-50 years who have achieved viral suppression did not have increased cIMT when compared to HIV-uninfected controls in Botswana. However, well-controlled HIV was associated with excess monocyte activation. Future work should explore the impact of subclinical atherosclerosis on CVD events among HIV-infected and -uninfected adults

  19. Pre-clinical carotid atherosclerosis and sCD163 among virally suppressed HIV patients in Botswana compared with uninfected controls.

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    Mosepele Mosepele

    Full Text Available Human immune deficiency virus (HIV is associated with increased cardiovascular disease (CVD risk, yet the relationship between HIV and carotid atherosclerosis / monocyte activation among virally suppressed HIV-infected patients in sub-Saharan Africa is not well understood.We measured traditional CVD risk factors, bilateral distal common carotid intima media thickness (cIMT, presence of carotid plaque and plasma sCD163 levels among virally suppressed HIV-infected adults and HIV-uninfected controls, in a cross-sectional study in Gaborone, Botswana. The associations between HIV status, traditional CVD risk factors, sCD163 and outcome of cIMT were assessed in univariate and multivariate linear regression models.We enrolled 208 HIV-infected adults (55% Female, mean age 39 years who had undetectable HIV-1 RNA on antiretroviral therapy and 224 HIV-uninfected controls (47% Female, mean age 37 years. There was no difference in cIMT between study groups, with mean cIMT 0.607mm and 0.599mm in HIV-infected and HIV-uninfected, respectively (p = 0.37. Plasma sCD163 was significantly higher in HIV-infected versus HIV-uninfected persons (1917ng/ml vs 1593ng/ml, p = 0.003, but was not associated with cIMT (p = 0.43 among all, p = 0.72 for HIV-infected only. In the final multivariate model, increased cIMT was associated with older age, being treated for hypertension, and higher non-HDL cholesterol among all (p<0.001, p = 0.03, p<0.001 respectively, and with older age and waist-hip ratio in HIV-infected participants (p = 0.02 & p = 0.02 respectively. Carotid plaque was present in a significantly higher proportion of HIV-infected adults (RR 2.15, 95% CI 1.22, 3.81.HIV-infected participants aged 30-50 years who have achieved viral suppression did not have increased cIMT when compared to HIV-uninfected controls in Botswana. However, well-controlled HIV was associated with excess monocyte activation. Future work should explore the impact of subclinical atherosclerosis

  20. Extracts from Acacia catechu suppress HIV-1 replication by inhibiting the activities of the viral protease and Tat

    Science.gov (United States)

    2013-01-01

    Background Acacia catechu (Mimosa family) stem bark extracts have been used traditionally as a dietary supplement as well as a folk medicine given its reported anti-inflammatory, immunomodulatory, hepatoprotective, antioxidant, anti-microbial and anti-tumor activities. The present study was undertaken to evaluate the anti-HIV-1 activity of the extracts from stem bark of A. catechu. Methods The aqueous and 50% ethanolic extracts of A. catechu stem bark were prepared and 50% ethanolic extract was further fractioned by successively partitioning with petroleum ether, chloroform and n-butanol. All the extracts and fractions were evaluated for cytotoxicity and anti-HIV-1 activity using different in vitro assays. The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro-viral genome integration and viral Tat protein mediated transactivation. The effect of n-butanol fraction on the induction of pro-inflammatory cytokines secretion in Vk2/E6E7 cells and transepithelial resistance in Caco-2 and HEC-1A cells was investigated. Results The aqueous and 50% ethanolic extracts of A. catechu showed IC50 values of 1.8 ± 0.18 μg/ml and 3.6 ± 0.31 μg/ml, respectively in cell-free virus based assay using TZM-bl cells and HIV-1NL4.3 (X-4 tropic). In the above assay, n-butanol fraction exhibited anti-HIV-1 activity with an IC50 of 1.7 ± 0.12 μg/ml. The n-butanol fraction showed a dose-dependent inhibition against HIV-1NL4.3 infection of the peripheral blood lymphocytes and against HIV-1BaL(R-5-tropic) as well as two different primary viral isolates of HIV-1 infection of TZM-bl cells. The n-butanol fraction demonstrates a potent inhibitory activity against the viral protease (IC50 = 12.9 μg/ml), but not reverse transcriptase or integrase. Further, in Alu-PCR no effect on viral integration was observed. The n-butanol fraction interfered with the Tat-mediated Long Terminal Repeat transactivation in

  1. High levels of adherence and viral suppression in a nationally representative sample of HIV-infected adults on antiretroviral therapy for 6, 12 and 18 months in Rwanda.

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    Batya Elul

    Full Text Available BACKGROUND: Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART in Africa. METHODS: We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL measurements. Multivariable logistic regression examined predictors of non-perfect (40 copies/ml. RESULTS: Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months; younger age; reporting severe (vs. no or few side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL; alcohol use; and attending sites which initiated ART services in 2003-2004 and 2005 (vs. 2006-2007; sites with ≥600 (vs. <600 patients on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. CONCLUSIONS: High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.

  2. Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial.

    Science.gov (United States)

    Kamwesiga, Julius; Mutabazi, Vincent; Kayumba, Josephine; Tayari, Jean-Claude K; Uwimbabazi, Jean Claude; Batanage, Gad; Uwera, Grace; Baziruwiha, Marcel; Ntizimira, Christian; Murebwayire, Antoinette; Haguma, Jean Pierre; Nyiransabimana, Julienne; Nzabandora, Jean Bosco; Nzamwita, Pascal; Mukazayire, Ernestine

    2015-06-01

    To examine the effect of selenium supplementation on CD4 T-cell counts, viral suppression, and time to antiretroviral therapy (ART) initiation in ART-naive HIV-infected patients in Rwanda. A multicenter, double-blinded, placebo-controlled, randomized clinical trial was conducted. Eligible patients were HIV-infected adults (≥21 years) who had a CD4 cell count between 400 and 650 cells/μl (ART eligibility was ≤350 cells/μl throughout the trial), and were willing to practice barrier methods of birth control. Patients were randomized to receive once-daily 200 μg selenium tablets or identical placebo. They were followed for 24 months with assessments every 6 months. Declines in CD4 cell counts were modeled using linear regressions with generalized estimating equations and effect modification, and the composite outcome (ART eligible or ART initiation) using Cox proportional-hazards regression, both conducted with intention to treat. Of the 300 participants, 149 received selenium, 202 (67%) were women, and median age was 33.5 years. The rate of CD4 depletion was reduced by 43.8% [95% confidence interval (CI) 7.8-79.8% decrease] in the treatment arm - from mean 3.97 cells/μl per month to mean 2.23 cells/μl per month. We observed 96 composite outcome events - 45 (47%) in the treatment arm. We found no treatment effect for the composite outcome (hazard ratio 1.00, 95% CI 0.66-1.54) or viral suppression (odds ratio 1.18, 95% CI 0.71-1.94). The trial was underpowered for the composite outcome due to a lower-than-anticipated event rate. Adverse events were comparable throughout. This randomized clinical trial demonstrated that 24-month selenium supplementation significantly reduces the rate of CD4 cell count decline among ART-naive patients.

  3. The HIV Care Cascade from HIV diagnosis to viral suppression in sub-Saharan Africa: a systematic review and meta-regression analysis protocol.

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    Gueler, Aysel; Vanobberghen, Fiona; Rice, Brian; Egger, Matthias; Mugglin, Catrina

    2017-08-25

    In 2014, UNAIDS announced the 90-90-90 treatment targets to curb the HIV epidemic by 2020: 90% of people living with HIV know their HIV status, 90% of people who know their HIV status access treatment and 90% of people on treatment have suppressed viral loads. Monitoring and evaluation are needed to track linkage and retention throughout the continuum of care. We propose a systematic review and meta-regression to identify the different methodological approaches used to define the steps in the HIV care cascade in sub-Saharan Africa (SSA), where most people with HIV live, and to assess the proportion of participants retained at each step. We will include cohort and cross-sectional studies published between 2004 and 2016 that report on the HIV care cascade among adults in SSA. The PubMed, Embase and CINAHL databases will be searched. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility and extract data. Disagreements will be resolved by consensus or consultation with a third reviewer. We will assess the number and proportion of individuals retained in the HIV care cascade from HIV diagnosis to linkage to care, engagement in pre-ART care, initiation of ART, retention on ART, and viral suppression. The data will be analysed using random effects meta-regression analysis. Publication bias will be assessed by funnel plots. This review will contribute to a better understanding of the HIV care cascade in SSA. It will help programs identify gaps and approaches to improve care and treatment for people living with HIV and reduce HIV transmission. PROSPERO CRD42017055863.

  4. Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice.

    Science.gov (United States)

    Tang-Feldman, Yajarayma J; Lochhead, G Raymond; Lochhead, Stephanie R; Yu, Cindy; Pomeroy, Claire

    2011-03-01

    To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.

  5. Poor CD4 response despite viral suppression is associated with increased non-AIDS-related mortality among HIV patients and their parents

    DEFF Research Database (Denmark)

    Pedersen, Gitte

    2013-01-01

    INTRODUCTION:: poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS related morbidity and on mortality in HIV patients and their parents. METHODS:: mortality rates were estimated among 1,758 virally suppre...... is associated with mortality among their parents, thus poor CD4 response may be caused by genetic factors, which might also affect morbidity and mortality in the HIV negative population.......INTRODUCTION:: poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS related morbidity and on mortality in HIV patients and their parents. METHODS:: mortality rates were estimated among 1,758 virally...... suppressed patients in the Danish HIV Cohort Study after two years on HAART and among their parents (n=1,603). Analyses were stratified by pre-HAART CD4 count and CD4 increase. Incidence rate ratios of non-AIDS-related morbidity and mortality rate ratios (MRR) were analyzed using Poisson regression. RESULTS...

  6. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study.

    Science.gov (United States)

    Trottier, Benoît; Lake, Jordan E; Logue, Ken; Brinson, Cynthia; Santiago, Lizette; Brennan, Clare; Koteff, Justin A; Wynne, Brian; Hopking, Judy; Granier, Catherine; Aboud, Michael

    2017-01-01

    Simplified dosing regimens are important for patients who face challenges in adhering to HIV-1 therapy. We investigated the safety and virological efficacy of switching to once-daily abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). The STRIIVING study was a randomized, open-label, Phase IIIb study in adults with HIV-1 RNA ART) at enrolment (ClinicalTrials.gov identifier, NCT02105987). Subjects were randomly assigned to switch to ABC/DTG/3TC once daily for 48 weeks (early-switch group) or continue current ART for 24 weeks and then switch to ABC/DTG/3TC (late-switch group). The primary end point was the proportion of subjects with HIV-1 RNA ART. At week 24, 85% and 88% of subjects who switched to ABC/DTG/3TC or remained on current ART, respectively, were virologically suppressed, indicating that ABC/DTG/3TC was non-inferior (difference in proportion, -3.4%; 95% CI -9.1, 2.4). At week 48, 83% and 92% were virologically suppressed in the early- and late-switch groups, respectively. Adverse events were reported more frequently with ABC/DTG/3TC (66%) than with current ART (47%) by week 24, and in the late-switch group, 60% of subjects reported adverse events post-switch. Pharmacokinetic data supported immediate switch. HIV Treatment Satisfaction Questionnaire scores improved in participants switching to ABC/DTG/3TC versus current ART. Data demonstrating non-inferiority of switching to ABC/DTG/3TC versus continuing current ART support ABC/DTG/3TC as an option when considering switch regimens in HIV-1-infected adults with stable viral suppression.

  7. Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study.

    Science.gov (United States)

    Cruz, Maria L S; Cardoso, Claudete A A; Darmont, Mariana Q; Souza, Edvaldo; Andrade, Solange D; D'Al Fabbro, Marcia M; Fonseca, Rosana; Bellido, Jaime G; Monteiro, Simone S; Bastos, Francisco I

    2014-01-01

    To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV) patients followed in pediatric centers in Brazil. This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF), anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL)<50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL<50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL<50 copies/mL (p ≤ 0.01). Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR=0.49; 95% CI: 0.27-0.89) and median interval between pharmacy visits<33 days (OR=0.97; 95% CI: 0.95-0.98) were independently associated with VL<50 copies/mL; whereas lower caregiver scores for anxiety (OR=2.57; 95% CI: 1.27-5.19) and children's HIV diagnosis for screening due to maternal infection (OR=2.25; 95% CI: 1.12-4.50) were found to be independently associated with 100% adherence. Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. Viral suppression and adherence among HIV-infected children and adolescents on antiretroviral therapy: results of a multicenter study

    Directory of Open Access Journals (Sweden)

    Maria L.S. Cruz

    2014-12-01

    Full Text Available OBJECTIVE: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV patients followed in pediatric centers in Brazil. METHODS: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers' quality of life (WHOQOL-BREF, anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL < 50 copies/mL. Statistical analyses included contingency tables and respective statistics, and multivariable logistic regression. RESULTS: 260 subjects were enrolled: 78% children and 22% adolescents; 93% of caregivers for the children and 77% of adolescents reported 100% adherence; 57% of children and 49% of adolescents had VL < 50 copies/mL. In the univariate analyses, HIV diagnosis for screening due to maternal infection, lower caregiver scores for anxiety, and higher scores in physical and psychological domains of WHOQOL-BREF were associated with 100% adherence. Shorter intervals between pharmacy visits were associated with VL < 50 copies/mL (p ≤ 0.01. Multivariable regression demonstrated that caregivers who did not abuse alcohol/other drugs (OR = 0.49; 95% CI: 0.27-0.89 and median interval between pharmacy visits < 33 days (OR = 0.97; 95% CI: 0.95-0.98 were independently associated with VL < 50 copies/mL; whereas lower caregiver scores for anxiety (OR = 2.57; 95% CI: 1.27-5.19 and children's HIV diagnosis for screening due to maternal infection (OR = 2.25; 95% CI: 1.12-4.50 were found to be independently associated with 100% adherence. CONCLUSIONS: Pediatric HIV programs should perform routine assessment of caregivers' quality of life, and anxiety and depression symptoms. In this setting, pharmacy records are essential to help identify less-than-optimal adherence.

  9. Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis.

    Science.gov (United States)

    Guo, Xiang; Higgs, Brandon W; Bay-Jensen, Anne-Christine; Wu, Yuling; Karsdal, Morten A; Kuziora, Michael; Godwood, Alex; Close, David; Ryan, Patricia C; Roskos, Lorin K; White, Wendy I

    2018-01-01

    Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate mechanisms of action and identify peripheral biomarkers associated with therapeutic responses of GM-CSF antagonism in RA. A 24-week placebo (PBO)-controlled trial was conducted in 305 RA patients who received mavrilimumab (30, 100 or 150 mg) or PBO once every 2 weeks. Serum biomarkers and whole blood gene expression profiles were measured by protein immunoassay and whole genome microarray. Mavrilimumab treatment induced significant down-regulation of type IV collagen formation marker (P4NP 7S), macrophage-derived chemokine (CCL22), IL-2 receptor α and IL-6 compared with PBO. Both early and sustained reduction of P4NP 7S was associated with clinical response to 150 mg mavrilimumab treatment. Gene expression analyses demonstrated reduced expression of transcripts enriched in macrophage and IL-22/IL-17 signalling pathways after GM-CSF blockade therapy. Myeloid and T cell-associated transcripts were suppressed in mavrilimumab-treated ACR20 responders but not non-responders. While CCL22 and IL-6 down-regulation may reflect a direct effect of GM-CSFR blockade on the production of pro-inflammatory mediators by myeloid cells, the suppression of IL-2 receptor α and IL-17/IL-22 associated transcripts suggests an indirect suppressive effect of mavrilimumab on T cell activation. Our results demonstrated association of peripheral biomarker changes with therapeutic response to mavrilimumab in RA patients. The sustained efficacy of mavrilimumab in RA may result from both direct effects on myeloid cells and indirect effects on T cell activation after GM-CSFR blockade.

  10. Randomized Controlled Trial of an Intervention to Maintain Suppression of HIV Viremia After Prison Release: The imPACT Trial.

    Science.gov (United States)

    Wohl, David A; Golin, Carol E; Knight, Kevin; Gould, Michele; Carda-Auten, Jessica; Groves, Jennifer S; Napravnik, Sonia; Cole, Stephen R; White, Becky L; Fogel, Cathie; Rosen, David L; Mugavaro, Michael J; Pence, Brian W; Flynn, Patrick M

    2017-05-01

    HIV-infected individuals transitioning from incarceration to the community are at risk for loss of viral suppression. We compared the effects of imPACT, a multidimensional intervention to promote care engagement after release, to standard care on sustaining viral suppression after community re-entry. This trial randomized 405 HIV-infected inmates being released from prisons in Texas and North Carolina with HIV-1 RNA levels HIV-1 RNA HIV-1 RNA 0.99). Higher rates of HIV suppression and medical care engagement than expected based on previous literature were observed among HIV-infected patients with suppressed viremia released from prison. Randomization to a comprehensive intervention to motivate and facilitate HIV care access after prison release did not prevent loss of viral suppression. A better understanding of the factors influencing prison releasees' linkage to community care, medication adherence, and maintenance of viral suppression is needed to inform policy and other strategic approaches to HIV prevention and treatment.

  11. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  12. Suppression of sputtering of nickel by coverage with self-sustaining thin segregated carbon layers

    Energy Technology Data Exchange (ETDEWEB)

    Morita, K.; Tsuchiya, T.; Hayashibara, M.; Itoh, N. (Nagoya Univ. (Japan). Dept. of Crystalline Materials Science)

    1983-05-01

    Sputtering of two-layered films composed of nickel ( proportional 5000 A) and nickel carbine ( proportional1500 A) at 600/sup 0/C by 5 keV Ar/sup +/ bombardment on the nickel side has been studied using Rutherford backscattering of 1.3 MeV H/sup +/ ions. It is found that the removal rate of nickel atoms from specimens is dependent on ion current density and that the removal rate of nickel atoms is very much smaller than that of carbon atoms when the ion current density is low. During ion bombardment at a low current density carbon segregation by a thickness of nearly two monolayers is observed at the nickel surface. Thus suppression of the removal rate of nickel atoms is ascribed to coverage of the nickel surface with segregated carbon atoms which are continuously supplied by diffusion through the nickel film from the carbide layer.

  13. Genetics and Genomics of Cotton Leaf Curl Disease, Its Viral Causal Agents and Whitefly Vector: A Way Forward to Sustain Cotton Fiber Security

    Directory of Open Access Journals (Sweden)

    Mehboob-ur- Rahman

    2017-07-01

    Full Text Available Cotton leaf curl disease (CLCuD after its first epidemic in 1912 in Nigeria, has spread to different cotton growing countries including United States, Pakistan, India, and China. The disease is of viral origin—transmitted by the whitefly Bemisia tabaci, which is difficult to control because of the prevalence of multiple virulent viral strains or related species. The problem is further complicated as the CLCuD causing virus complex has a higher recombination rate. The availability of alternate host crops like tomato, okra, etc., and practicing mixed type farming system have further exaggerated the situation by adding synergy to the evolution of new viral strains and vectors. Efforts to control this disease using host plant resistance remained successful using two gene based-resistance that was broken by the evolution of new resistance breaking strain called Burewala virus. Development of transgenic cotton using both pathogen and non-pathogenic derived approaches are in progress. In future, screening for new forms of host resistance, use of DNA markers for the rapid incorporation of resistance into adapted cultivars overlaid with transgenics and using genome editing by CRISPR/Cas system would be instrumental in adding multiple layers of defense to control the disease—thus cotton fiber production will be sustained.

  14. Reported Church Attendance at the Time of Entry into HIV Care is Associated with Viral Load Suppression at 12 Months.

    Science.gov (United States)

    Van Wagoner, Nicholas; Elopre, Latesha; Westfall, Andrew O; Mugavero, Michael J; Turan, Janet; Hook, Edward W

    2016-08-01

    The Southeast has high rates of church attendance and HIV infection rates. We evaluated the relationship between church attendance and HIV viremia in a Southeastern US, HIV-infected cohort. Viremia (viral load ≥200 copies/ml) was analyzed 12 months after initiation of care. Univariate and multivariable logistic regression models were fit for variables potentially related to viremia. Of 382 patients, 74 % were virally suppressed at 12 months. Protective variables included church attendance (AOR 0.5; 95 % CI 0.2, 0.9), being on antiretroviral therapy (AOR 0.01; 95 % CI 0.004, 0.04), CD4(+) T lymphocyte count 200-350 cells/mm(3) at care entry (AOR 0.3; 95 % 0.1, 0.9), and education (AOR 0.5; 95 % CI 0.2, 0.9). Variables predicting viremia included black race (AOR 3.2; 95 % CI 1.4, 7.4) and selective disclosure of HIV status (AOR 2.7; 95 % CI 1.2, 5.6). Church attendance may provide needed support for patients entering HIV care for the first time. El Sur Este de los Estados Unidos tiene tasas altas de visitas a iglesias y de infección por VIH. Evaluamos la relación entre visitas a iglesias y viremia por VIH en una cohorte de pacientes infectados con VIH en el Sur Este de los EEUU. La viremia (carga viral ≥ 200 copias/ml) fue analizada a los 12 meses de iniciar el cuidado médico. Los modelos de regresión logística univariado y multivariado fueron ajustados para variables potencialmente relacionadas a viremia. De 382 pacientes, 75 % tuvieron supresión virológica a los 12 meses. Variables que ofrecieron protección fueron visitas a iglesias (AOR 0.5; IC95 % 0.2-0.9), recibir terapia antiretroviral (AOR 0.01; IC95 % 0.004,0.04), recuento de linfocitos T CD4 + 200-350 al iniciar cuidado médico (AOR 0.3; IC95 % 0.1,09), y educación (AOR 0.5; IC95 % 0.2,0.9). Las variables que predijeron viremia incluyeron raza negra (AOR 3.2; IC95 % 1.4,7.4) y la comunicación selectiva del diagnóstico de VIH a otras personas (AOR 2.7; 95 % IC 1

  15. Depression and anxiety were low amongst virally suppressed, long-term treated HIV-infected individuals enrolled in a public sector antiretroviral program in Thailand.

    Science.gov (United States)

    Prasithsirikul, Wisit; Chongthawonsatid, Sukanya; Ohata, Pirapon June; Keadpudsa, Siriwan; Klinbuayaem, Virat; Rerksirikul, Patsamon; Kerr, Stephen J; Ruxrungtham, Kiat; Ananworanich, Jintanat; Avihingsanon, Anchalee

    2017-03-01

    HIV/AIDS and anxiety/depression are interlinked. HIV-infected patients suffering from depression may be at risk for poor adherence which may contribute to HIV disease progression. Additionally, an HIV diagnosis and/or using certain antiretroviral agents may trigger symptoms of anxiety/depression. The objective of the study was to assess the prevalence and factors associated with anxiety and depression in HIV-infected patients from the Thai National HIV Treatment Program. This cross-sectional study was performed from January 2012 to December 2012 in HIV-infected out-patients, aged ≥18 years, from three HIV referral centers. Symptoms of anxiety and depression were measured using the Thai-validated Hospital Anxiety and Depression Scale (HADS). A score of ≥11 was defined as having anxiety and depression. Associated factors were assessed by multivariate logistic regression. Totally 2023 (56% males) patients were enrolled. All patients received antiretroviral therapy (ART) for a mean duration of 7.7 years. Median CD4 was 495 cells/mm(3). Ninety-five percent had HIV-RNA depression were 4.8% and 3.1%, respectively. About 1.3% had both anxiety and depression. In multivariate logistic models, the female sex [OR = 1.6(95%CI 1.1-2.3), p = .01], having adherence depression. Our findings demonstrated that prevalence of depression and anxiety was low amongst virally suppressed, long-term antiretroviral-treated HIV-infected individuals. Some key characteristics such as the female sex, poor adherence, poor/fair QOL and EFV exposure are associated with anxiety and depression. These factors can be used to distinguish who would need a more in-depth evaluation for these psychiatric disorders.

  16. Role of Gay Neighborhood Status and Other Neighborhood Factors in Racial/Ethnic Disparities in Retention in Care and Viral Load Suppression Among Men Who Have Sex with Men, Florida, 2015.

    Science.gov (United States)

    Mauck, Daniel E; Sheehan, Diana M; Fennie, Kristopher P; Maddox, Lorene M; Trepka, Mary Jo

    2018-01-25

    This study's objective was to examine the role of gay neighborhood residence and other neighborhood factors in racial/ethnic disparities in retention in HIV care and viral load suppression during 2015. Florida residents diagnosed 2000-2014 with HIV infection and with transmission mode of men who have sex with men (MSM) were included in multi-level logistic regression models. Of 29,156 MSM, 29.4% were not retained and 34.2% were not virally suppressed. Non-Hispanic Blacks (NHB) had a higher likelihood of not being retained (adjusted prevalence ratio [aPR] 1.31, 95% confidence interval [CI] 1.24-1.38, p value < 0.0001) and not being virally suppressed (aPR 1.82, 95% CI 1.67-1.98, p value < 0.0001) compared with non-Hispanic Whites. Among NHBs, rural residence was protective for both outcomes. Although gay neighborhood residence was not associated with either outcome, the role of other neighborhood factors suggests that individual and neighborhood barriers to HIV care and treatment should be addressed among MSM.

  17. Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

    Directory of Open Access Journals (Sweden)

    Jin-Lu Liu

    2016-05-01

    Full Text Available AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein (Gen-NLC to inhibit human lens epithelial cells (HLECs proliferation. METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size (PS, zeta potentials (ZP, encapsulation efficiency (EE and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier (NLC, genistein (Gen and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8 (CCK-8 assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR and immunofluorescence analyses. RESULTS: The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was -7.14±0.38 mV and the EE of Gen in the nanoparticles was 92.3%±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The mRNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group. CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth.

  18. IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C.

    Science.gov (United States)

    Zhong, Yan-Wei; Zhang, Hong-Fei; Shi, Yan-Min; Li, Yong-Li; Chu, Fang; Xu, Zhi-Qiang; Chen, Da-Wei; Gan, Yu; Wang, Fu-Chuan; Gu, Mei-Lei; Dong, Yi; Zhu, Shi-Shu; Shi, Ce; Fan, Hua-Hao; Zhang, Xiu-Chang; Zhang, Min

    2016-01-01

    Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m(2) 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×10(5) IU/ml) and higher baseline viral load group(≥6×10(5) IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.

  19. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  20. T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

    Science.gov (United States)

    Utzschneider, Daniel T; Charmoy, Mélanie; Chennupati, Vijaykumar; Pousse, Laurène; Ferreira, Daniela Pais; Calderon-Copete, Sandra; Danilo, Maxime; Alfei, Francesca; Hofmann, Maike; Wieland, Dominik; Pradervand, Sylvain; Thimme, Robert; Zehn, Dietmar; Held, Werner

    2016-08-16

    Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination.

    Directory of Open Access Journals (Sweden)

    Kai Hu

    Full Text Available The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality.

  2. A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination

    Science.gov (United States)

    Hu, Kai; Harris, Deshea L.; Yamaguchi, Takefumi; von Andrian, Ulrich H.; Hamrah, Pedram

    2015-01-01

    The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality. PMID:26332302

  3. Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

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    Antonio Rivero-Juarez

    Full Text Available AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6. Rapid and sustained virological response (RVR and SVR rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03. Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031. With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02, RVR (p = 0.015 and SVR (p = 0.029 than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

  4. HSP70 induced by Hantavirus infection interacts with viral nucleocapsid protein and its overexpression suppresses virus infection in Vero E6 cells.

    Science.gov (United States)

    Yu, Lu; Ye, Ling; Zhao, Rong; Liu, Yan Fang; Yang, Shou Jing

    2009-07-15

    Hantavirus (HTV) infection is known to induce innate cellular response, a more specified cellular response in the host cells. However, whether it stimulates synthesis of stress proteins, particularly associations of viral proteins, is entirely unknown. The primary focus of this research is using Vero E6 cells infected with Hantaan 76-118 (HTNV) as an in vitro infection model to examine the individual contribution of HTV infection to heat shock response. This study shows that HTNV infection rapidly induced HSP70 expression in Vero E6 cells, which underwent a nucleo-cytoplasmic shuttle that lasted for more than 3 d. The increased HSP70 was preceded by induction of HSP70 mRNA. The physical association of HSP70 with viral nucleocapsid protein (NP) in infected cells was demonstrated by co-localization and immunoprecipation. Vero E6 cells that constitutively overexpress HSP70 after stable transfection with HSP70 gene, when infected with HTNV, showed selectively reduced NP synthesis. These findings suggest HSP70 is actively involved in the control of the expression level of viral structural proteins and possibly involved in virus assembly by binding of NP to HSP70. Overexpression of HSP70 does not favor viral propagation.

  5. Sustained suppression of type-I edge-localized modes with dominantly n = 2 magnetic fields in DIII-D

    Science.gov (United States)

    Lanctot, M. J.; Buttery, R. J.; de Grassie, J. S.; Evans, T. E.; Ferraro, N. M.; Hanson, J. M.; Haskey, S. R.; Moyer, R. A.; Nazikian, R.; Osborne, T. H.; Orlov, D. M.; Snyder, P. B.; Wade, M. R.; the DIII-D Team

    2013-08-01

    Type-I edge-localized modes (ELMs) have been suppressed in DIII-D (Luxon et al 2003 Nucl. Fusion 43 1813) H-mode discharges with a H98Y2 confinement factor near 1.0 using magnetic perturbations (MPs) with dominant toroidal mode number n = 2. This expands access to the ELM-suppressed regime, which was previously attainable in DIII-D only with n = 3 fields. ELM suppression is obtained with two rows of internal coils for 1.8 s with normalized beta of 1.9 and average triangularity of 0.53, corresponding to a scaled version of ITER scenario 2 at an ITER relevant electron collisionality of 0.2. The applied field reduces the pedestal pressure and edge current via the density without degrading the edge thermal transport barrier. ELITE calculations find that the resulting profiles are stable to intermediate-n peeling-ballooning modes. ELM suppression is found within different ranges of q95 depending on the coil configuration used to generate the MP. The edge safety factors associated with suppression do not correspond to those that maximize the pitch-resonant components of the applied vacuum field. Instead, ELM suppression is correlated with an increase in the amplification of kink-resonant components of the calculated ideal MHD plasma response field.

  6. Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

    OpenAIRE

    Siliciano Robert F; Hegarty Robert W; O'Connell Karen A; Blankson Joel N

    2011-01-01

    Abstract Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he devel...

  7. Viral encephalitis

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    Marcus Tulius T Silva

    2013-09-01

    Full Text Available While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

  8. Viral marketing

    OpenAIRE

    Bláhová, Adéla

    2012-01-01

    The aim of my thesis is to provide a comprehensive overview of the viral marketing and to analyze selected viral campaigns. There is a description of advantages and disadvantages of this marketing tool. In the end I suggest for which companies viral marketing is an appropriate form of the promotion.

  9. Viral phylodynamics.

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    Erik M Volz

    Full Text Available Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viralphylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread[2], spatio-temporal dynamics including metapopulation dynamics[3], zoonotic transmission, tissue tropism[4], and antigenic drift[5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics.

  10. Effects of Interferon-α/β on HBV Replication Determined by Viral Load

    Science.gov (United States)

    Tian, Yongjun; Chen, Wen-ling; Ou, Jing-hsiung James

    2011-01-01

    Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low. PMID:21829354

  11. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

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    Melanie Thompson

    Full Text Available GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA boost vaccine (GOVX-B11, was undertaken in HIV infected participants on antiretroviral treatment (ART to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI. Nine men who began antiretroviral therapy (ART within 18 months of seroconversion and had sustained plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine.clinicaltrials.gov NCT01378156.

  12. Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.

    Science.gov (United States)

    Hua, Stéphane; Lécuroux, Camille; Sáez-Cirión, Asier; Pancino, Gianfranco; Girault, Isabelle; Versmisse, Pierre; Boufassa, Faroudy; Taulera, Olivier; Sinet, Martine; Lambotte, Olivier; Venet, Alain

    2014-01-01

    HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status. We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated. Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], P = 0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], P = 0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], P = 0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations. These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.

  13. Potential Role for HIV-Specific CD38−/HLA-DR+ CD8+ T Cells in Viral Suppression and Cytotoxicity in HIV Controllers

    Science.gov (United States)

    Hua, Stéphane; Lécuroux, Camille; Sáez-Cirión, Asier; Pancino, Gianfranco; Girault, Isabelle; Versmisse, Pierre; Boufassa, Faroudy; Taulera, Olivier; Sinet, Martine; Lambotte, Olivier; Venet, Alain

    2014-01-01

    Background HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38−/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status. Materials and Methods We compared CD38−/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated. Results Compared to CD38+/HLA-DR+ cells, CD38−/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134–462] vs 638 [307–747], P = 0.001), higher frequency of polyfunctional cells (15% [7%–33%] vs 21% [16%–43%], P = 0.0003), greater proliferative capacity (0-fold [0–2] vs 3-fold [2]–[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%–11%] vs 13% [6%–22%], P = 0.02). The CD38−/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations. Conclusions These data highlight the role of CD38−/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies. PMID:25000587

  14. Potato Virus Y HCPro Suppression of Antiviral Silencing in Nicotiana benthamiana Plants Correlates with Its Ability To Bind In Vivo to 21- and 22-Nucleotide Small RNAs of Viral Sequence.

    Science.gov (United States)

    Del Toro, Francisco J; Donaire, Livia; Aguilar, Emmanuel; Chung, Bong-Nam; Tenllado, Francisco; Canto, Tomás

    2017-06-15

    We have investigated short and small RNAs (sRNAs) that were bound to a biologically active hexahistidine-tagged Potato virus Y (PVY) HCPro suppressor of silencing, expressed from a heterologous virus vector in Nicotiana benthamiana plants, and purified under nondenaturing conditions. We found that RNAs in purified preparations were differentially enriched in 21-nucleotide (nt) and, to a much lesser extent, 22-nt sRNAs of viral sequences (viral sRNAs [vsRNAs]) compared to those found in a control plant protein background bound to nickel resin in the absence of HCPro or in a purified HCPro alanine substitution mutant (HCPro mutB) control that lacked suppressor-of-silencing activity. In both controls, sRNAs were composed almost entirely of molecules of plant sequence, indicating that the resin-bound protein background had no affinity for vsRNAs and also that HCPro mutB failed to bind to vsRNAs. Therefore, PVY HCPro suppressor activity correlated with its ability to bind to 21- and 22-nt vsRNAs. HCPro constituted at least 54% of the total protein content in purified preparations, and we were able to calculate its contribution to the 21- and the 22-nt pools of sRNAs present in the purified samples and its binding strength relative to the background. We also found that in the 21-nt vsRNAs of the HCPro preparation, 5'-terminal adenines were overrepresented relative to the controls, but this was not observed in vsRNAs of other sizes or of plant sequences.IMPORTANCE It was previously shown that HCPro can bind to long RNAs and small RNAs (sRNAs) in vitro and, in the case of Turnip mosaic virus HCPro, also in vivo in arabidopsis AGO2-deficient plants. Our data show that PVY HCPro binds in vivo to sRNAs during infection in wild-type Nicotiana benthamiana plants when expressed from a heterologous virus vector. Using a suppression-of-silencing-deficient HCPro mutant that can accumulate in this host when expressed from a virus vector, we also show that sRNA binding correlates

  15. Five-year follow-up of patients with chronic C hepatitis and sustained virological response Seguimiento a 5 años de pacientes con hepatitis crónica C y respuesta viral sostenida

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    I. Puig-del-Castillo

    2011-02-01

    Full Text Available Objective: to assess persistence of sustained viral response at 5 years of follow-up in patients with chronic viral hepatitis C treated with pegylated interferon and ribavirin. Design: a descriptive study. Patients: from August 2001 to May 2004, all patients treated at our center with pegylated interferon and ribavirin who achieved a sustained viral response were consecutively enrolled (93 patients. Demographic, histological, biochemical, and virological data were collected during treatment and 5 years after achievement of the sustained viral response. Eighty-six percent of patients enrolled (n = 80 attended the control visit at 5 years. Results: mean age of enrolled patients was 41 years (standard deviation = 10 years, and 30.1% (n = 28 were women. Liver biopsy had been performed before treatment in 68.8% of patients (n = 64, showing no or mild fibrosis in 62.3% (F0 and F1 and significant fibrosis and cirrhosis in 37.7% (F ≥ 3. Genotype distribution was: 58.1% genotype 1 (n = 54; 8.6% genotype 2 (n = 8; 24.7% genotype 3 (n = 23; 7.5% genotype 4 (n = 7, and indeterminate in one patient. Only one patient experienced virological recurrence. All other patients had negative HCV RNA levels and, in the absence of other liver diseases, normal ALT levels. Conclusion: in patients treated with pegylated interferon and ribavirin with sustained viral response, long-term recurrence rate was very low.Objetivo: evaluar la persistencia de respuesta viral sostenida a los 5 años de seguimiento en pacientes con hepatitis crónica por virus C tratados con interferón pegilado y ribavirina. Diseño: estudio descriptivo. Pacientes: desde agosto de 2001 hasta mayo de 2004, se incluyeron de forma consecutiva todos los pacientes de nuestro centro tratados con interferón pegilado y ribavirina que alcanzaron respuesta viral sostenida (93 pacientes. Se recogieron datos demográficos, histológicos, bioquímicos y virológicos durante el tratamiento y a los 5 años de

  16. Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins.

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    Wenyan Zhang

    Full Text Available BACKGROUND: APOBEC3G (A3G and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized. METHODS AND FINDINGS: In the present study, we have demonstrated that the regions of APOBEC3F (A3F that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE. CONCLUSIONS: Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors.

  17. Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.

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    Jessica Nyström

    Full Text Available Microbial translocation (MT contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS, lipopolysaccharide binding protein (LBP and soluble CD14 (sCD14 could predict anti-HCV treatment outcome.Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART treatment were categorized into sustained viral responders (SVR; n = 21 or non-responders (NR; n = 15 based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24 and mono-infected (HIV; n = 18, based on the HCV infection status. Samples were collected before start (at baseline of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV or antiretroviral-therapy and two years after treatment start (at follow up. χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004 and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07.In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART may be a more relevant MT marker than LPS and sCD14.

  18. First-line cART regimen impacts the course of CD8+ T-cell counts in HIV-infected patients that achieve sustained undetectable viral load.

    Science.gov (United States)

    Poizot-Martin, Isabelle; Allavena, Clotilde; Delpierre, Cyrille; Duvivier, Claudine; Obry-Roguet, Véronique; Cano, Carla E; Guillouet de Salvador, Francine; Rey, David; Dellamonica, Pierre; Cheret, Antoine; Cuzin, Lise; Katlama, Christine; Cabié, André; Hoen, Bruno

    2016-10-01

    The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 T-cell counts in human immunodeficiency virus (HIV)-infected patients.A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients.We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 T-cell counts according to cART regimen was assessed.CD8 T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 T-cell count compared with NNRTI-containing regimens (-10.2 cells/μL in 3NRTIs vs -105.1 cells/μL; P=0.02) but not compared with PI-containing regimens (10.2 vs -60.9 cells/μL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 T-cell count and % compared with PI/r- and NNRTI-containing regimens (0.2 in 3NRTIs vs -9.9 with PI/r-regimens, P=0.001, and vs -11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 T-cell count of -155 [inter quartile range: -302; -22] cells/μL.Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation.

  19. T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication

    DEFF Research Database (Denmark)

    Erikstrup, Christian; Kronborg, Gitte; Lohse, Nicolai

    2010-01-01

    INTRODUCTION: CD4 T-cell recovery is impeded in some HIVinfected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients. METHODS: In the Danish HIV Cohort Study, we identified HIV-1......28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P , 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production...... of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production....

  20. Initial suboptimal CD4 reconstitution with antiretroviral therapy despite full viral suppression in a cohort of HIV-infected patients in Senegal.

    Science.gov (United States)

    Batista, G; Buvé, A; Ngom Gueye, N F; Manga, N M; Diop, M N; Ndiaye, K; Thiam, A; Ly, F; Diallo, A; Ndour, C T; Seydi, M

    2015-06-01

    We determined the risk factors and incidence of clinical events associated with suboptimal immune reconstitution (SIR) defined by an increase in CD4 inferior to 50 cells/μL, from inclusion up to six months of antiretroviral treatment (ARVT), in patients with an undetectable viral load ( 40 years (aOR = 1.74, 95% CI = 1.10-2.75), baseline CD4 ≥ 100 cells/μL (aOR = 2.06, 95% CI = 1.24-3.42), ARVT including AZT (aOR = 4.57, 95% CI=1.06-19.76), and the occurrence of a severe opportunistic infection during the first semester of ARVT (aOR = 2.38 95% CI= 1.49-3.80) were associated with SIR. After six months of ARVT and up to seven years of follow-up, 39 patients with SIR had presented with an opportunistic infection or death (rate= 9.78/100 person-years) compared to 168 with a normal recovery (rate = 7.75/100 person-years) but the difference was not statistically significant (aHR = 1.22, 95% CI = 0.85 to 1.74). SIR is less common in our country and is not associated with increased mortality or a greater incidence of opportunistic infections after six months of ARVT. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. High CD8+ T cell activation marks a less differentiated HIV-1 specific CD8+ T cell response that is not altered by suppression of viral replication.

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    Jason D Barbour

    Full Text Available The relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults.We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1 Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28- phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-, low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28- HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004. In turn, those with the highest fraction of intermediate memory (CD27+ CD28- HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01, indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment.A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile.

  2. Pemasaran ViralViral Marketing

    OpenAIRE

    Situmorang, James Rianto

    2010-01-01

    Viral marketing is an extremely powerful and effective form of internet marketing. Itis a new form of word-of-mouth through internet. In viral marketing, someone passeson a marketing message to someone else and so on. Viral marketing proposes thatmessages can be rapidly disseminated from consumer to consumer leading to largescale market acceptance. The analogy of a virus is used to described the exponentialdiffusion of information in an electronic environment and should not be confusedwith th...

  3. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study.

    Science.gov (United States)

    Caniglia, Ellen C; Cain, Lauren E; Sabin, Caroline A; Robins, James M; Logan, Roger; Abgrall, Sophie; Mugavero, Michael J; Hernández-Díaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R; Seage, George R; Bonnet, Fabrice; Dabis, Francois; Moore, Richard D; Reiss, Peter; van Sighem, Ard; Mathews, William C; Del Amo, Julia; Moreno, Santiago; Deeks, Steven G; Muga, Roberto; Boswell, Stephen L; Ferrer, Elena; Eron, Joseph J; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Justice, Amy C; Tate, Janet P; Gill, John; Pacheco, Antonio; Veloso, Valdilea G; Bucher, Heiner C; Egger, Matthias; Furrer, Hansjakob; Porter, Kholoud; Touloumi, Giota; Crane, Heidi; Miro, Jose M; Sterne, Jonathan A; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A

    2017-06-01

    Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of

  4. Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.

    Directory of Open Access Journals (Sweden)

    Satoshi Sekiguchi

    Full Text Available Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV, is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid-polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis, liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25, which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/-/MxCre((+/- mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor TNF-α and (interleukin IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.

  5. Non-Disclosure of HIV Status and Associations with Psychological Factors, ART Non-Adherence, and Viral Load Non-Suppression Among People Living with HIV in the UK.

    Science.gov (United States)

    Daskalopoulou, Marina; Lampe, Fiona C; Sherr, Lorraine; Phillips, Andrew N; Johnson, Margaret A; Gilson, Richard; Perry, Nicky; Wilkins, Ed; Lascar, Monica; Collins, Simon; Hart, Graham; Speakman, Andrew; Rodger, Alison J

    2017-01-01

    Disclosure of HIV status to family, friends, and a stable partner may be linked to improved health outcomes for people living with HIV. This study assessed whether non-disclosure is associated with psychological symptoms, non-adherence to antiretroviral therapy (ART), and viral load (VL) non-suppression. A total of 3258 HIV-diagnosed individuals in the UK completed the confidential ASTRA study questionnaire (2011-2012). Participants reported whether they told anyone they had HIV; to which confidant(s) (friends, family, work colleagues, stable partner) and to what extent (none, some, most/all). The prevalence and factors associated with non-disclosure were assessed. Associations between non-disclosure and the following factors were established using modified Poisson regression with adjustment for socio-demographic factors (gender, age group, ethnicity), HIV-related factors (time since HIV diagnosis, ART status), and clinic: low social support (score ≤ 12 on modified Duke-UNC FSSQ); depression and anxiety symptoms (≥10 on PHQ-9 and GAD-7 respectively); self-reported ART non-adherence in past 2 weeks/3 months; VL non-suppression (clinic-recorded VL > 50 copies/mL among those who started ART ≥ 6 months ago). Among 3233 participants with disclosure data, the prevalence of non-disclosure to anyone was 16.6 % (n/N = 61/367) among heterosexual men, 15.7 % (98/626) among women, and 5.0 % (113/2240) among MSM. MSM were more likely to disclose to some/all friends compared to family (85.8 vs. 59.9 %) while heterosexuals were less likely to disclose to friends than family (44.1 vs. 61.1 % for men, 57.5 vs. 67.1 % for women). Among 1,631 participants with a stable partner, non-disclosure to a stable partner was 4.9 % for MSM, 10.9 % for heterosexual men, and 13.0 % for women. In adjusted analyses, older age (≥60 years), non-white ethnicity, more recent HIV diagnosis, and not having a stable partner were significantly associated with overall non

  6. Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-κB via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells.

    Science.gov (United States)

    Lee, Jin-Woo; Kim, Young Il; Im, Chang-Nim; Kim, Sung Wan; Kim, Su Jin; Min, Seoyeon; Joo, Yong Hoon; Yim, Sung-Vin; Chung, Namhyun

    2017-06-07

    Airway epithelial cells are often infected by respiratory syncytial virus (RSV), one of the most common causes of asthma, bronchiolitis, chronic obstructive pulmonary disease, and pneumonia. During the infection process, excessive mucins instigate airway inflammation. However, the mechanism underlying RSV-induced airway hyper-responsiveness and inflammation is poorly understood. Furthermore, no reliable vaccines or drugs for antiviral therapy are available. In this study, the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV-infected human airway epithelial cells A549 was evaluated. After pretreatment of the cells with or without exposure to RSV with 5-10 μg GSP/mL, the expression of various mucins (MUC1, MUC2, MUC5AC, MUC5B, and MUC8) was evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting, as well as confocal microscopy. We found that GSP significantly decreased RSV-induced mucin synthesis at the mRNA and protein levels. In addition, GSP suppressed the RSV-induced signaling pathways, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together with nuclear factor kappa B (NF-κB) and activating protein-1 family members (c-Jun and c-Fos). Concomitantly, GSP inhibited the replication of RSV within A549 cells. Taken together, all our results suggest that GSP could be a potent therapeutic agent to suppress excessive mucus production and viral replication in RSV-induced airway inflammatory disorders.

  7. Viral Hepatitis

    Science.gov (United States)

    ... Us FAQs Ask a Question Toll Free Numbers Homeless Veterans Chat VA » Health Care » Viral Hepatitis » Veterans and ... Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning Service Members Rural Veterans Seniors & Aging Veterans ...

  8. Short-term retinoic acid treatment sustains pluripotency and suppresses differentiation of human induced pluripotent stem cells.

    Science.gov (United States)

    De Angelis, Maria Teresa; Parrotta, Elvira Immacolata; Santamaria, Gianluca; Cuda, Giovanni

    2018-01-05

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) derived from blastocyst and human induced pluripotent stem cells (hiPSCs) generated from somatic cells by ectopic expression of defined transcriptional factors, have both the ability to self-renew and to differentiate into all cell types. Here we explored the two antagonistic effects of retinoic acid (RA) on hiPSCs. Although RA has been widely described as a pharmacological agent with a critical role in initiating differentiation of pluripotent stem cells, we demonstrate that short-term RA exposure not only antagonizes cell differentiation and sustains pluripotency of hiPSCs, but it also boosts and improves their properties and characteristics. To shed light on the mechanistic insights involved in the resistance to differentiation of hiPSCs cultured in RA conditions, as well as their improved pluripotency state, we focused our attention on the Wnt pathway. Our findings show that RA inhibits the Wnt canonical pathway and positively modulates the Akt/mTOR signaling, explaining why such perturbations, under our experimental conditions, do not lead to hiPSCs differentiation. Altogether, these data uncover a novel role for RA in favouring the maintenance of ground-state pluripotency, supporting its bivalent role, dose- and time-dependent, for hiPSCs differentiation and self-renewal processes.

  9. Switch to Rilpivirine/Emtricitabine/Tenofovir Single-Tablet Regimen of Human Immunodeficiency Virus-1 RNA-Suppressed Patients, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales CO3 Aquitaine Cohort, 2012-2014.

    Science.gov (United States)

    Cazanave, Charles; Reigadas, Sandrine; Mazubert, Cyril; Bellecave, Pantxika; Hessamfar, Mojgan; Le Marec, Fabien; Lazaro, Estibaliz; Peytavin, Gilles; Bruyand, Mathias; Fleury, Hervé; Dabis, François; Neau, Didier

    2015-01-01

    Background.  The purpose of this study was to assess the efficacy and tolerability of combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-1 virologically suppressed patients who switched to rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) as a single-tablet regimen (STR). Methods.  A retrospective multicenter cohort study was performed between September 2012 and February 2014 in Bordeaux University Hospital-affiliated clinics. Patients with a plasma HIV viral load (VL) lower than 50 copies/mL and switching to STR were evaluated at baseline, 3, 6, 9, and 12 months from switch time (M3, M6, M9, M12) for VL and other biological parameters. Change from baseline in CD4 cell counts was evaluated at M6 and M12. Virological failure (VF) was defined as 2 consecutive VL >50 copies/mL. Results.  Three hundred four patients were included in the analysis. Single-tablet regimen switch was proposed to 116 patients with adverse events, mostly efavirenz (EFV)-based (n = 59), and to 224 patients for cART simplification. Thirty of 196 patients with available genotype resistance test results displayed virus with ≥1 drug resistance mutation on reverse-transcriptase gene. After 12 months of follow-up, 93.4% (95.5% confidence interval, 89.9-96.2) of patients remained virologically suppressed. There was no significant change in CD4 cell count. During the study period, 5 patients experienced VF, one of them harboring RPV resistance mutation. Clinical cART tolerability improved in 79 patients overall (29.9%) at M6, especially neurological symptoms related to EFV. Fasting serum lipid profiles improved, but a significant estimated glomerular function rate decrease (-11 mL/min/1.73 m(2); P < 10(-4)) was observed. Conclusions.  Overall, virologic suppression was maintained in patients after switching to RPV/TDF/ FTC. This STR strategy was associated with improved tolerability.

  10. Hepatic sarcoidosis complicating treatment-naive viral hepatitis

    OpenAIRE

    Aravinthan, Aloysious; Gelson, William; Limbu, Anita; Brais, Rebecca; Richardson, Paul

    2012-01-01

    Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis ...

  11. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.......Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  12. Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

    Directory of Open Access Journals (Sweden)

    Carolina Stenfeldt

    Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

  13. Valuable Virality

    NARCIS (Netherlands)

    Akpinar, E.; Berger, Jonah

    2017-01-01

    Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how

  14. Viral Gastroenteritis

    Science.gov (United States)

    ... help relieve the symptoms of viral gastroenteritis in adults: drinking plenty of liquids such as fruit juices, sports ... as the child is hungry giving infants breast milk or full strength ... solutions Older adults and adults with weak immune systems should also ...

  15. Viral pathogens.

    Science.gov (United States)

    Ragni, M V; Sherman, K E; Jordan, J A

    2010-07-01

    Despite continuous improvement in safety and purity of blood products for individuals with haemophilia, transmissible agents continue to affect individuals with haemophilia. This chapter addresses three viral pathogens with significant clinical impact: HIV, hepatitis C and parvovirus B19. Hepatitis C is the leading cause of chronic hepatitis and the major co-morbid complication of haemophilia treatment. Clinically, asymptomatic intermittent alanine aminotransferase elevation is typical, with biopsy evidence of advanced fibrosis currently in 25%. Current treatment is effective in up to 70%, and many new agents are in development. For those progressing to end-stage liver disease, liver transplantation outcomes are similar to those in non-haemophilia subjects, although pretransplant mortality is higher. HIV infection, the second leading co-morbid condition in haemophilia, is managed as a chronic infection with highly active antiretroviral therapy (HAART). HAART also slows hepatitis C virus (HCV) progression in those with HIV/HCV co-infection. Viral inactivation and recombinant technologies have effectively prevented transfusion-transmitted viral pathogens in haemophilia. Human parvovirus B19 infection, typically associated with anaemia or, rarely severe aplastic crisis, is a non-lipid enveloped virus, for which standard inactivation techniques are ineffective. Thus, nucleic acid testing (NAT) to screen the blood supply for B19 DNA is currently under consideration by the Food and Drug Administration. To the extent, viral inactivation, recombinant, and NAT technologies are available worldwide, and the lifespan for those with haemophilia is approaching that of the normal population. The purpose of this chapter is to provide an update on three clinically significant transfusion-transmitted viral pathogens.

  16. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  17. T Cell Exhaustion During Persistent Viral Infections

    Science.gov (United States)

    Kahan, Shannon M.; Wherry, E. John; Zajac, Allan J.

    2015-01-01

    Although robust and highly effective anti-viral T cells contribute to the clearance of many acute infections, viral persistence is associated with the development of functionally inferior, exhausted, T cell responses. Exhaustion develops in a step-wise and progressive manner, ranges in severity, and can culminate in the deletion of the anti-viral T cells. This disarming of the response is consequential as it compromises viral control and potentially serves to dampen immune-mediated damage. Exhausted T cells are unable to elaborate typical anti-viral effector functions. They are characterized by the sustained upregulation of inhibitory receptors and display a gene expression profile that distinguishes them from prototypic effector and memory T cell populations. In this review we discuss the properties of exhausted T cells; the virological and immunological conditions that favor their development; the cellular and molecular signals that sustain the exhausted state; and strategies for preventing and reversing exhaustion to favor viral control. PMID:25620767

  18. Viral epigenetics.

    Science.gov (United States)

    Milavetz, Barry I; Balakrishnan, Lata

    2015-01-01

    DNA tumor viruses including members of the polyomavirus, adenovirus, papillomavirus, and herpes virus families are presently the subject of intense interest with respect to the role that epigenetics plays in control of the virus life cycle and the transformation of a normal cell to a cancer cell. To date, these studies have primarily focused on the role of histone modification, nucleosome location, and DNA methylation in regulating the biological consequences of infection. Using a wide variety of strategies and techniques ranging from simple ChIP to ChIP-chip and ChIP-seq to identify histone modifications, nuclease digestion to genome wide next generation sequencing to identify nucleosome location, and bisulfite treatment to MeDIP to identify DNA methylation sites, the epigenetic regulation of these viruses is slowly becoming better understood. While the viruses may differ in significant ways from each other and cellular chromatin, the role of epigenetics appears to be relatively similar. Within the viral genome nucleosomes are organized for the expression of appropriate genes with relevant histone modifications particularly histone acetylation. DNA methylation occurs as part of the typical gene silencing during latent infection by herpesviruses. In the simple tumor viruses like the polyomaviruses, adenoviruses, and papillomaviruses, transformation of the cell occurs via integration of the virus genome such that the virus's normal regulation is disrupted. This results in the unregulated expression of critical viral genes capable of redirecting cellular gene expression. The redirected cellular expression is a consequence of either indirect epigenetic regulation where cellular signaling or transcriptional dysregulation occurs or direct epigenetic regulation where epigenetic cofactors such as histone deacetylases are targeted. In the more complex herpersviruses transformation is a consequence of the expression of the viral latency proteins and RNAs which again can

  19. Viral Infection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  20. Viral bronchiolitis.

    Science.gov (United States)

    Florin, Todd A; Plint, Amy C; Zorc, Joseph J

    2017-01-14

    Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection.

    Science.gov (United States)

    Knuschke, Torben; Rotan, Olga; Bayer, Wibke; Sokolova, Viktoriya; Hansen, Wiebke; Sparwasser, Tim; Dittmer, Ulf; Epple, Matthias; Buer, Jan; Westendorf, Astrid M

    2016-04-14

    Regulatory T cells (Tregs) have been shown to limit anti-viral immunity during chronic retroviral infection and to restrict vaccine-induced T cell responses. The objective of the study was to assess whether a combinational therapy of nanoparticle-based therapeutic vaccination and concomitant transient ablation of Tregs augments anti-viral immunity and improves virus control in chronically retrovirus-infected mice. Therefore, chronically Friend retrovirus (FV)-infected mice were immunized with calcium phosphate (CaP) nanoparticles functionalized with TLR9 ligand CpG and CD8(+) or CD4(+) T cell epitope peptides (GagL85-93 or Env gp70123-141) of FV. In addition, Tregs were ablated during the immunization process. Reactivation of CD4(+) and CD8(+) effector T cells was analysed and the viral loads were determined. Therapeutic vaccination of chronically FV-infected mice with functionalized CaP nanoparticles transiently reactivated cytotoxic CD8(+) T cells and significantly reduced the viral loads. Transient ablation of Tregs during nanoparticle-based therapeutic vaccination strongly enhanced anti-viral immunity and further decreased viral burden. Our data illustrate a crucial role for CD4(+) Foxp3(+) Tregs in the suppression of anti-viral T cell responses during therapeutic vaccination against chronic retroviral infection. Thus, the combination of transient Treg ablation and therapeutic nanoparticle-based vaccination confers robust and sustained anti-viral immunity.

  2. Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

    Science.gov (United States)

    Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J

    2017-08-01

    Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

  3. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy

    Directory of Open Access Journals (Sweden)

    Ángela Puente

    Full Text Available Background and aims: The regression of liver fibrosis and portal hypertension (PH and their influence on the natural history of compensated hepatitis C virus (HCV-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR on the portal pressure gradient (HVPG and non-invasive parameters of PH and prognostic factors of response. Methods: Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules. A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. Results: In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case and a decrease of < 3 log at week 8 (two patients. Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively. The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5% and a Fibroscan® < 7.1 kPa in three patients (37.5%. Conclusions: Complete hemodynamic response (HVPG < 6 mmHg and fibrosis regression (Fibroscan® < 7.1 kPa occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

  4. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy.

    Science.gov (United States)

    Puente, Ángela; Cabezas, Joaquín; López Arias, María Jesús; Fortea, José Ignacio; Arias, María Teresa; Estébanez, Ángel; Casafont, Fernando; Fábrega, Emilio; Crespo, Javier

    2017-01-01

    The regression of liver fibrosis and portal hypertension (PH) and their influence on the natural history of compensated hepatitis C virus (HCV)-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR) on the portal pressure gradient (HVPG) and non-invasive parameters of PH and prognostic factors of response. Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg) without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules). A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case) and a decrease of < 3 log at week 8 (two patients). Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively). The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5%) and a Fibroscan® < 7.1 kPa in three patients (37.5%). Complete hemodynamic response (HVPG < 6 mmHg) and fibrosis regression (Fibroscan® < 7.1 kPa) occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

  5. CTL Escape and Viral Fitness in HIV/SIV Infection.

    Science.gov (United States)

    Seki, Sayuri; Matano, Tetsuro

    2011-01-01

    Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence.

  6. What is the impact of a country-wide scale-up in antiviral therapy on the characteristics and sustained viral response rates of patients treated for hepatitis C?

    Science.gov (United States)

    McDonald, Scott A; Innes, Hamish A; Hayes, Peter C; Dillon, John F; Mills, Peter R; Goldberg, David J; Barclay, Stephen; Allen, Sam; Fox, Ray; Fraser, Andrew; Kennedy, Nicholas; Bhattacharyya, Diptendu; Hutchinson, Sharon J

    2015-02-01

    The global burden associated with hepatitis C virus (HCV) infection has prompted a scale-up of antiviral therapy. Hitherto, no data exist on the impact of scaling-up, on the characteristics of treated populations, or on sustained viral response (SVR) rates. We assessed the country-wide scale-up of antiviral therapy in Scotland, a country which nationally monitors uptake of and response to HCV treatment. Data for patients, initiated on combined pegylated interferon and ribavirin therapy at 13 specialist HCV clinics in 2001-2010, were extracted from the Scottish HCV Clinical Database (n=3895). Patient characteristics included age, genotype, PWID (people who inject drugs) status, prison referral, and diagnosed cirrhosis. Temporal trends in covariates and adjusted effects on a SVR were examined via mixed-effects regression. The number of patients starting treatment increased from 237 in 2001-2002 to 1560 in 2009-2010, with an increasing trend in SVR from 44% to 57% over this period. For a given clinic, between 2001/2 and 2010 there was a decrease in the odds of those treated being diagnosed with cirrhosis (odds ratio [OR]=0.84 per year), and increasing temporal trends for those treated being PWID (OR=1.08) and prison referrals (OR=1.06). Adjusting for covariates, the proportion of a given clinic's patients achieving SVR was positively associated with the percentage of PWID (OR=1.01 per percent increase; 95% confidence interval [CI]: 1.00-1.02) and genotype 2/3 (OR=1.03; 95% CI: 1.02-1.04). Despite changes in patient characteristics, a country-wide scale-up of antiviral therapy did not compromise SVR rates. Results are highly relevant to countries planning on scaling-up treatment, given the forthcoming availability of new interferon-free therapies. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. [Viral superantigens].

    Science.gov (United States)

    Us, Dürdal

    2016-07-01

    , expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been

  8. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

    NARCIS (Netherlands)

    Caniglia, Ellen C.; Cain, Lauren E.; Sabin, Caroline A.; Robins, James M.; Logan, Roger; Abgrall, Sophie; Mugavero, Michael J.; Hernández-Díaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard D.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Justice, Amy C.; Tate, Janet P.; Gill, John; Pacheco, Antonio; Veloso, Valdilea G.; Bucher, Heiner C.; Egger, Matthias; Furrer, Hansjakob; Porter, Kholoud; Touloumi, Giota; Crane, Heidi; Miro, Jose M.; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2017-01-01

    Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data

  9. Viral Skin Diseases.

    Science.gov (United States)

    Ramdass, Priya; Mullick, Sahil; Farber, Harold F

    2015-12-01

    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The case for viral load testing in adolescents in resource-limited settings.

    Science.gov (United States)

    Marcus, Rebecca; Ferrand, Rashida A; Kranzer, Katharina; Bekker, Linda-Gail

    2017-11-01

    The success of HIV treatment programmes globally has resulted in children with perinatally acquired HIV reaching adolescence in large numbers. The number of adolescents living with HIV is growing further due to persisting high HIV incidence rates among adolescents in low- and middle-income settings, particularly in sub-Saharan Africa. Although expanding access to HIV viral load monitoring is necessary to achieve the 90-90-90 targets across the HIV care continuum, implementation is incomplete. We discuss the rationale for prioritizing viral load monitoring among adolescents and the associated challenges. Adolescents with HIV are a complex group to treat successfully due to extensive exposure to antiretroviral therapy for those with perinatally acquired HIV and the challenges in sustained medication adherence in this age group. Given the high risk of treatment failure among adolescents and the limited drug regimens available in limited resource settings, HIV viral load monitoring in adolescents could prevent unnecessary and costly switches to second-line therapy in virologically suppressed adolescents. Because adolescents living with HIV may be heavily treatment experienced, have suboptimal treatment adherence, or may be on second or even third-line therapy, viral load testing would allow clinicians to make informed decisions about increased counselling and support for adolescents together with the need to maintain or switch therapeutic regimens. Given scarce resources, prioritization of viral load testing among groups with a high risk of virological failure may be required. Adolescents have disproportionately high rates of virological failure, and targeting this age group for viral load monitoring may provide valuable lessons to inform broader scale-up. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

  11. Viral lysis of

    NARCIS (Netherlands)

    Lønborg, C.; Middelboe, M.; Brussaard, C.P.D.

    2013-01-01

    The viral mediated transformation of phytoplankton organic carbon to dissolved forms (“viral shunt”) has been suggested as a major source of dissolved organic carbon (DOC) in marine systems. Despite the potential implications of viral activity on the global carbon fluxes, studies investigating

  12. Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial

    Science.gov (United States)

    2011-01-01

    Background Low levels of serum selenium are associated with increased risk of mortality among HIV+ patients in East Africa. We aim to assess the effect of selenium supplementation on CD4 cell count, HIV viral load, opportunistic infections, and quality of life in HIV-infected patients in Rwanda. Methods and Design A 24-month, multi-centre, patient and provider-blinded, randomized, placebo-controlled clinical trial involving 300 pre-antiretroviral therapy (ART) HIV-infected patients will be carried out at two sites in Rwanda. Patients ≥ 21 years of age with documented HIV infection, CD4 cell count of 400-650 cells/mm3, and not yet on ART will be recruited. Patients will be randomized at each study site using a randomized block design to receive either the selenium micronutrient supplement or an identically appearing placebo taken once daily. The primary outcome is a composite of time from baseline to reduction of CD4 T lymphocyte count below 350 cells/mm3 (confirmed by two measures at least one week apart), or start of ART, or the emergence of a documented CDC-defined AIDS-defining illness. An intention-to-treat analysis will be conducted using stepwise regression and structural equation modeling. Discussion Micronutrient interventions that aim to improve CD4 cell count, decrease opportunistic infections, decrease HIV viral load, and ultimately delay initiation of more costly ART may be beneficial, particularly in resource-constrained settings, such as sub-Saharan Africa. Additional trials are needed to determine if micro-supplementation can delay the need for more costly ART among HIV-infected patients. If shown to be effective, selenium supplementation may be of public health importance to HIV-infected populations, particularly in sub-Saharan Africa and other resource-constrained settings. Trial Registration NCT01327755 PMID:21838913

  13. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  14. Novel small-molecule inhibitors of hepatitis C virus entry block viral spread and promote viral clearance in cell culture.

    Directory of Open Access Journals (Sweden)

    Glen A Coburn

    Full Text Available Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp technology. We independently discovered and optimized a series of 1,3,5-triazine compounds that are potent, selective and non-cytotoxic inhibitors of HCV entry. Representative compounds fully suppress both cell-free virus and cell-to-cell spread of HCV in vitro. We demonstrate, for the first time, that long term treatment of an HCV cell culture with a potent entry inhibitor promotes sustained viral clearance in vitro. We have confirmed that a single amino acid variant, V719G, in the transmembrane domain of E2 is sufficient to confer resistance to multiple compounds from the triazine series. Resistance studies were extended by evaluating both the fusogenic properties and growth kinetics of drug-induced and natural amino acid variants in the HCVpp and HCV cell culture assays. Our results indicate that amino acid variations at position 719 incur a significant fitness penalty. Introduction of I719 into a genotype 1b envelope sequence did not affect HCV entry; however, the overall level of HCV replication was reduced compared to the parental genotype 1b/2a HCV strain. Consistent with these findings, I719 represents a significant fraction of the naturally occurring genotype 1b sequences. Importantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection.

  15. Viral Marketing Past Present Future

    OpenAIRE

    Nessipbekova, Zarina

    2010-01-01

    The work studies the viral marketing. These are past viral campaigns, viral campaigns today, and evaluates their actuality. The work tries to predict the development of viral marketing on the basis of the research done by the author.

  16. The new normal: immunomodulatory agents against sepsis immune suppression.

    Science.gov (United States)

    Hutchins, Noelle A; Unsinger, Jacqueline; Hotchkiss, Richard S; Ayala, Alfred

    2014-04-01

    Sepsis is the leading cause of death among critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the proinflammatory stage have failed clinically; therefore, new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as interleukin-7 (IL-7), IL-15, granulocyte macrophage colony-stimulating factor (GM-CSF), as well as co-inhibitory molecule blockade, such as anti-programmed cell death receptor-1 (anti-PD-1) and anti-B and T lymphocyte attenuator (anti-BTLA), may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Thought suppression.

    Science.gov (United States)

    Wenzlaff, R M; Wegner, D M

    2000-01-01

    Although thought suppression is a popular form of mental control, research has indicated that it can be counterproductive, helping assure the very state of mind one had hoped to avoid. This chapter reviews the research on suppression, which spans a wide range of domains, including emotions, memory, interpersonal processes, psychophysiological reactions, and psychopathology. The chapter considers the relevant methodological and theoretical issues and suggests directions for future research.

  18. Effectiveness, pharmacokinetics, and safety of a new sustained-release leuprolide acetate 3.75-mg depot formulation for testosterone suppression in patients with prostate cancer: a Phase III, open-label, international multicenter study.

    Science.gov (United States)

    Marberger, Michael; Kaisary, Amir V; Shore, Neal D; Karlin, Gary S; Savulsky, Claudio; Mis, Ricard; Leuratti, Chiara; Germa, Josep R

    2010-04-01

    A microencapsulated, sustained-release formulation of leuprolide acetate 3.75 mg has been developed. This study investigated the effectiveness, pharmacokinetics, and safety profile of a 1-month leuprolide acetate 3.75-mg depot formulation for suppressing testosterone concentrations in patients with prostate cancer. This was a Phase III, open-label, international multicenter clinical trial. Patients with prostate cancer who, in the judgment of the investigators, could benefit from androgen deprivation therapy received 6 monthly intramuscular injections of leuprolide acetate 3.75-mg depot. Plasma testosterone concentrations were determined at specific times throughout the study. The primary end point was the proportion of successful patients over the total number of evaluable patients (ie, patients with evaluable testosterone concentrations at all monthly assessments and no missing values due to treatment-related adverse events). Treatment success was defined as testosterone suppression below the clinical castration level (ie, suppression by day 21. By day 28, 96.8% (151/156) of the evaluable patients had achieved castrate levels, and 73.1% (114/156) achieved testosterone concentrations <0.2 ng

  19. Viral Entry into Cells

    Science.gov (United States)

    D'Orsogna, Maria R.

    2010-09-01

    Successful viral infection of a healthy cell requires complex host-pathogen interactions. In this talk we focus on the dynamics specific to the HIV virus entering a eucaryotic cell. We model viral entry as a stochastic engagement of receptors and coreceptors on the cell surface. We also consider the transport of virus material to the cell nucleus by coupling microtubular motion to the concurrent biochemical transformations that render the viral material competent for nuclear entry. We discuss both mathematical and biological consequences of our model, such as the formulation of an effective integrodifferential boundary condition embodying a memory kernel and optimal timing in maximizing viral probabilities.

  20. Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and CD8⁺ T-cell exhaustion.

    Directory of Open Access Journals (Sweden)

    Myeong Sup Lee

    Full Text Available The type I interferons (IFN-Is are critical not only in early viral control but also in prolonged T-cell immune responses. However, chronic viral infections such as those of human immunodeficiency virus (HIV and hepatitis C virus (HCV in humans and lymphocytic choriomeningitis virus (LCMV in mice overcome this early IFN-I barrier and induce viral persistence and exhaustion of T-cell function. Although various T-cell-intrinsic and -extrinsic factors are known to contribute to induction of chronic conditions, the roles of IFN-I negative regulators in chronic viral infections have been largely unexplored. Herein, we explored whether 2'-5' oligoadenylate synthetase-like 1 (OASL1, a recently defined IFN-I negative regulator, plays a key role in the virus-specific T-cell response and viral defense against chronic LCMV. To this end, we infected Oasl1 knockout and wild-type mice with LCMV CL-13 (a chronic virus and monitored T-cell responses, serum cytokine levels, and viral titers. LCMV CL-13-infected Oasl1 KO mice displayed a sustained level of serum IFN-I, which was primarily produced by splenic plasmacytoid dendritic cells, during the very early phase of infection (2-3 days post-infection. Oasl1 deficiency also led to the accelerated elimination of viremia and induction of a functional antiviral CD8 T-cell response, which critically depended on IFN-I receptor signaling. Together, these results demonstrate that OASL1-mediated negative regulation of IFN-I production at an early phase of infection permits viral persistence and suppresses T-cell function, suggesting that IFN-I negative regulators, including OASL1, could be exciting new targets for preventing chronic viral infection.

  1. IFITM proteins restrict viral membrane hemifusion.

    Directory of Open Access Journals (Sweden)

    Kun Li

    2013-01-01

    Full Text Available The interferon-inducible transmembrane (IFITM protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ, a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA, a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM. We observed that the generalized polarizations (GPs and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive

  2. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  3. Novel viral translation strategies.

    Science.gov (United States)

    Au, Hilda H T; Jan, Eric

    2014-01-01

    Viral genomes are compact and encode a limited number of proteins. Because they do not encode components of the translational machinery, viruses exhibit an absolute dependence on the host ribosome and factors for viral messenger RNA (mRNA) translation. In order to recruit the host ribosome, viruses have evolved unique strategies to either outcompete cellular transcripts that are efficiently translated by the canonical translation pathway or to reroute translation factors and ribosomes to the viral genome. Furthermore, viruses must evade host antiviral responses and escape immune surveillance. This review focuses on some recent major findings that have revealed unconventional strategies that viruses utilize, which include usurping the host translational machinery, modulating canonical translation initiation factors to specifically enhance or repress overall translation for the purpose of viral production, and increasing viral coding capacity. The discovery of these diverse viral strategies has provided insights into additional translational control mechanisms and into the viral host interactions that ensure viral protein synthesis and replication. © 2014 John Wiley & Sons, Ltd.

  4. Interocular suppression

    Science.gov (United States)

    Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

    2017-08-01

    The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

  5. Discovering hidden viral piracy.

    Science.gov (United States)

    Kim, Eddo; Kliger, Yossef

    2005-12-01

    Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.

  6. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

    Directory of Open Access Journals (Sweden)

    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

  7. Viral marketing on the Internet

    OpenAIRE

    Štverák, Martin

    2008-01-01

    Thesis provides an overview of viral marketing. It describes the process by which you can be inspired to implement viral campaign. The thesis includes analysis of specific viral Web project. The aim of this thesis is to create a breakdown of the various components of viral marketing, to establish conditions that should be satisfied for the viral marketing to success, suggesting how to use viral marketing on social network Facebook and evaluate the various components of this service for the pr...

  8. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  9. Viral Gastroenteritis (Stomach Flu)

    Science.gov (United States)

    ... Viral gastroenteritis (stomach flu) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  10. Viral hemorrhagic septicemia

    Science.gov (United States)

    Batts, William N.; Winton, James R.

    2012-01-01

    Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

  11. HIV Viral Load

    Science.gov (United States)

    ... Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle ... used each time. Will exercise, nutrition, and other lifestyle modifications help decrease my HIV viral load? There ...

  12. Treatment of viral encephalitis.

    Science.gov (United States)

    Domingues, Renan Barros

    2009-03-01

    Several viruses may cause central nervous system diseases with a broad range of clinical manifestations. The time course of the viral encephalitis can be acute, subacute, or chronic. Pathologically there are encephalitis with direct viral entry into the CNS in which brain parenchyma exhibits neuronal damaging and viral antigens and there are postinfectious autoimmune encephalitis associated with systemic viral infections with brain tissue presenting perivascular aggregation of immune cells and myelin damaging. Some virus affect previously healthy individuals while others produce encephalitis among imunocompromised ones. Factors such evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some viral encephalitis [e.g. West-Nile virus, and Japanese B virus]. Citomegalovirus and JC virus are examples of infections of the brain that have been seen more frequently because they occur in immunocompromised patients. In the other hand many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. In this article, we will present the current drug options in the management of the main acute and chronic viral infection of the central nervous system of immunocompetent and immunocompromised adults, focusing on drugs mechanisms of action, efficacy, and side effects. The early diagnosis and correct management of such diseases can reduce mortality and neurological sequelae; however, even with recent treatment advances, potentially devastating outcomes are still possible.

  13. Conditions for viral influence spreading through correlated multiplex networks

    CERN Document Server

    Hu, Yanqing; Makse, Hernán A

    2014-01-01

    A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up ``new ideas''. Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through ``viral'' influence spreading producing cascades of followers fragmenting an old network to create a new one. Typical examples include the raise of scientific ideas or abrupt changes in social media, like the raise of Facebook.com to the detriment of Myspace.com. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex correlated graph with hidden ``influence links''. Analytical solutions predict percolation phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of...

  14. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  15. VIRAL DISEASES IN SEA FISH

    OpenAIRE

    Ivančica Strunjak-Perović; Mato Hacmanjek; Rozelinda Čož-Rakovac; Emin Teskeredžić

    1996-01-01

    Adequate knowledge on fish diseases caused by viruses is still lacking. Up until now, in fish which live their entire life cycle or part of it in the sea, some viral diseases have been determined (lymphoeytis, viral necrosis of crythrocytes, ciravosti cod syndrome, encephalitis, viral hemoragic septichemistry, viral hematopoetic necrosis, viral gusteraca necrosis, chum renviral infection, branchionephritis, rabdociral eel infection). Some of these diseases primarily occur in the freshwater ph...

  16. Viral RNA Silencing Suppression: The Enigma of Bunyavirus NSs Proteins.

    Science.gov (United States)

    Hedil, Marcio; Kormelink, Richard

    2016-07-23

    The Bunyaviridae is a family of arboviruses including both plant- and vertebrate-infecting representatives. The Tospovirus genus accommodates plant-infecting bunyaviruses, which not only replicate in their plant host, but also in their insect thrips vector during persistent propagative transmission. For this reason, they are generally assumed to encounter antiviral RNA silencing in plants and insects. Here we present an overview on how tospovirus nonstructural NSs protein counteracts antiviral RNA silencing in plants and what is known so far in insects. Like tospoviruses, members of the related vertebrate-infecting bunyaviruses classified in the genera Orthobunyavirus, Hantavirus and Phlebovirus also code for a NSs protein. However, for none of them RNA silencing suppressor activity has been unambiguously demonstrated in neither vertebrate host nor arthropod vector. The second part of this review will briefly describe the role of these NSs proteins in modulation of innate immune responses in mammals and elaborate on a hypothetical scenario to explain if and how NSs proteins from vertebrate-infecting bunyaviruses affect RNA silencing. If so, why this discovery has been hampered so far.

  17. Viral RNA Silencing Suppression: The Enigma of Bunyavirus NSs Proteins

    Directory of Open Access Journals (Sweden)

    Marcio Hedil

    2016-07-01

    Full Text Available The Bunyaviridae is a family of arboviruses including both plant- and vertebrate-infecting representatives. The Tospovirus genus accommodates plant-infecting bunyaviruses, which not only replicate in their plant host, but also in their insect thrips vector during persistent propagative transmission. For this reason, they are generally assumed to encounter antiviral RNA silencing in plants and insects. Here we present an overview on how tospovirus nonstructural NSs protein counteracts antiviral RNA silencing in plants and what is known so far in insects. Like tospoviruses, members of the related vertebrate-infecting bunyaviruses classified in the genera Orthobunyavirus, Hantavirus and Phlebovirus also code for a NSs protein. However, for none of them RNA silencing suppressor activity has been unambiguously demonstrated in neither vertebrate host nor arthropod vector. The second part of this review will briefly describe the role of these NSs proteins in modulation of innate immune responses in mammals and elaborate on a hypothetical scenario to explain if and how NSs proteins from vertebrate-infecting bunyaviruses affect RNA silencing. If so, why this discovery has been hampered so far.

  18. [Vasculitis and viral infection].

    Science.gov (United States)

    Martínez Aguilar, N E; Guido Bayardo, R; Vargas Camaño, M E; Compañ González, D; Miranda Feria, A J

    1997-01-01

    Viruses have been implicated in vasculitis. To determine activity of viral infection associated with vasculitis. 17 patients with vasculitis had been in immunological and antiviral antibodies evaluation. Twenty five healthy controls sex and age matched with hematic biometry (BH) and AA. All subjects were negative to HIV and HBV. Viral activity was demonstrated in eight patients; vascular purpura (5), Takayasu disease (1), polyarteritis nodosa (1), erythema nodosum (1). None subject of control group had IgM activity. Antibodies response of IgG in patients were of lesser intensity than in control group. 14 abnormalities in BH were found in patients and 4 in control group. Immune response in patients, measured by lymphocyte subpopulations and circulating immune complexes was abnormal. In conclusion 47% showed viral activity, but the dominant feature was abnormal immune response in 82%.

  19. Modeling Viral Capsid Assembly

    Science.gov (United States)

    2014-01-01

    I present a review of the theoretical and computational methodologies that have been used to model the assembly of viral capsids. I discuss the capabilities and limitations of approaches ranging from equilibrium continuum theories to molecular dynamics simulations, and I give an overview of some of the important conclusions about virus assembly that have resulted from these modeling efforts. Topics include the assembly of empty viral shells, assembly around single-stranded nucleic acids to form viral particles, and assembly around synthetic polymers or charged nanoparticles for nanotechnology or biomedical applications. I present some examples in which modeling efforts have promoted experimental breakthroughs, as well as directions in which the connection between modeling and experiment can be strengthened. PMID:25663722

  20. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  1. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  2. Immigration and viral hepatitis.

    Science.gov (United States)

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Viral meningitis and encephalitis.

    Science.gov (United States)

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. HIV sexual transmission risks in the context of clinical care: a prospective study of behavioural correlates of HIV suppression in a community sample, Atlanta, GA, USA

    Directory of Open Access Journals (Sweden)

    Seth C Kalichman

    2015-08-01

    Full Text Available Introduction: Antiretroviral therapy (ART improves the health of people living with HIV and has the potential to reduce HIV infectiousness, thereby preventing HIV transmission. However, the success of ART for HIV prevention hinges on sustained ART adherence and avoiding sexually transmitted infections (STI. Objectives: To determine the sexual behaviours and HIV transmission risks of individuals with suppressed and unsuppressed HIV replication (i.e., viral load. Methods: Assessed HIV sexual transmission risks among individuals with clinically determined suppressed and unsuppressed HIV. Participants were 760 men and 280 women living with HIV in Atlanta, GA, USA, who completed behavioural assessments, 28-daily prospective sexual behaviour diaries, one-month prospective unannounced pill counts for ART adherence, urine screening for illicit drug use and medical record chart abstraction for HIV viral load. Results: Individuals with unsuppressed HIV demonstrated a constellation of behavioural risks for transmitting HIV to uninfected sex partners that included symptoms of STI and substance use. In addition, 15% of participants with suppressed HIV had recent STI symptoms/diagnoses, indicating significant risks for sexual infectiousness despite their HIV suppression in blood plasma. Overall, 38% of participants were at risk for elevated sexual infectiousness and just as many engaged in unprotected sexual intercourse with non-HIV-infected partners. Conclusions: Implementation strategies for using HIV treatments as HIV prevention requires enhanced behavioural interventions that extend beyond ART to address substance use and sexual health that will otherwise undermine the potential preventive impact of early ART.

  5. HIV and Viral Hepatitis

    Science.gov (United States)

    ... get some forms of viral hepatitis the same way you get HIV—through unprotected sexual contact and injection drug use. HAV, which causes a short-term but occasionally severe illness, is usually spread when the virus is ingested from contact with ...

  6. Immigration and viral hepatitis

    NARCIS (Netherlands)

    S. Sharma (Suraj); M. Carballo (Manuel); J.J. Feld (Jordan J.); H.L.A. Janssen (Harry)

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and

  7. VIRAL FEVER WITH THROMBOCYTOPENIA

    OpenAIRE

    Shilpa Anand Hakki

    2017-01-01

    BACKGROUND There is an alarming increase in the incidence of fever with thrombocytopenia especially during monsoon and peri-monsoon period. Infections with protozoa, bacteria and viruses can cause thrombocytopenia with or without disseminated intravascular coagulation. Commonly, dengue, malaria, scrub typhus and other rickettsial infections, meningococci, Leptospira and certain viral infections present as fever with thrombocytopenia. Occasionally, these patients can go on to devel...

  8. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  9. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  10. Neutrophil subset responses in infants with severe viral respiratory infection.

    Science.gov (United States)

    Cortjens, Bart; Ingelse, Sarah A; Calis, Job C; Vlaar, Alexander P; Koenderman, Leo; Bem, Reinout A; van Woensel, Job B

    2017-03-01

    Neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. Recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. Here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on CD16/CD62L expression. We show that during the course of severe respiratory infection infants may develop four heterogeneous neutrophil subsets in blood (mature, immature, progenitor, and suppressive neutrophils), each with distinct activation states. However, while isolated viral respiratory infection was characterized by a relative absence of suppressive neutrophils in both blood and lungs, only patients with bacterial co-infection were shown to produce suppressive neutrophils. These data suggest the occurrence of distinct and unique neutrophil subset responses during severe viral and (secondary) bacterial respiratory infection in infants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  12. PROFILE OF VIRAL CONJUCTIVITIS

    Directory of Open Access Journals (Sweden)

    Gopal Kishan

    2015-04-01

    Full Text Available INTRODUCTION : Viral conjunctivitis is most commonly seen in the outpatient department. A variety of viruses which are responsible for conjunctival infection , of which Adenovirus is the most common. It is highly contagious during the first 2 weeks of infection. It can cause corneal involvement within 4 - 5 days after the onset of symptoms. Corneal lesions range from SPK (Superficial Punctat e Keratitis to epithelial defects. These corneal lesions may cause intense photophobia and impairment of vision. AIM : To find out the commonest etiological agent , to study the clinical features and complications related to it. METHODOLOGY : This study was carried out prospectively. 100 patients who came to outpatient department between October 2013 to October 2014 were enrolled in the study. All the age groups and both the genders were included. Patients underwent slit lamp examination and were diagnosed cl inically. 25 cases were submitted for Gram staining and Polymerase Chain Reaction (PCR study to know the type of virus and serotype . RESULT : 100 patients were diagnosed with viral conjunctivitis and were kept on follow up. 21percent of patients developed SPK. Adenovirus 8 was found to be more common than other viruses. CONCLUSION : The present study showed Adeno virus to be the most common etiological agent causing viral conjunctivitis and complications like subepithelial opacities and diminished vision

  13. The new normal: immuno-modulatory agents against sepsis immune suppression

    Science.gov (United States)

    Hutchins, Noelle A.; Unsinger, Jacqueline; Hotchkiss, Richard S.; Ayala, Alfred

    2014-01-01

    Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as IL-7, IL-15, GM-CSF as well as co-inhibitory molecule blockade, such as anti-PD-1 and anti-BTLA, may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. PMID:24485901

  14. Cytokine mRNA profiles in bronchoalveolar cells of piglets experimentally infected in utero with porcine reproductive and respiratory syndrome virus: Association of sustained expression of IFN-gamma and IL-10 after viral clearance

    DEFF Research Database (Denmark)

    Johnsen, C. K.; Bøtner, Anette; Kamstrup, Søren

    2002-01-01

    An experimental model was used to investigate mRNA cytokine profiles in bronchoalvolar cells (BALC) from piglets, infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). The BALC's were analyzed for the cytokines TNF-alpha, IFN-gamma, IL-8, IL-10, and IL-12(p40) by real......-time TaqMan polymerase chain reaction in 2-, 4-, and 6-week-old piglets, respectively. High levels of IFN-gamma mRNA was detected in all piglets, while IL-10 was upregulated in 2-week-old piglets, was at normal levels in 4-week-old piglets, and elevated again in 6-week-old piglets. IL-12 was weakly...... elevated in all three age groups. Virus was reduced by 50% in 4-week-old piglets and cleared by 6 weeks of age. The sustained expression of IFNgamma and reduction of IL-10 production indicate an important role for these cytokines in immunity to PRRSV....

  15. Global viral hepatitis elimination by the year 2030

    Directory of Open Access Journals (Sweden)

    Richard Tjan

    2016-12-01

    Full Text Available According to a report by Stanaway et al.(1 in 2016, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. For example, the number of global deaths due to viral hepatitis increased from 0.89 million to 1.45 million, indicating a need for its reduction. In this connection, on 28 May 2016 the 69th World Health Assembly adopted the global health sector strategy on viral hepatitis for the period 2016–2021,(2 as outlined in the report A69/32 of the Secretariat,(3 with the goal of eliminating viral hepatitis B and C by the year 2030. The global health sector strategy (GHSS on viral hepatitis has constructed a roadmap toward the elimination of viral hepatitis B and C, targeting five priority prevention and treatment interventions. Prevention involves universal hepatitis B immunization of infants, prevention of mother-to-child transmission, increased injection safety and blood safety, and increased harm reduction, the implementation of which will contribute toward universal health coverage, which is the target for Goal 3 of the 2030 Agenda for Sustainable Development. In combination with treatment of chronic hepatitis, the goal is to achieve by the year 2030 a reduction in the incidence of viral hepatitis by 90% and mortality by 65%.(3,4

  16. HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection.

    Science.gov (United States)

    Jiang, Guochun; Santos Rocha, Clarissa; Hirao, Lauren A; Mendes, Erica A; Tang, Yuyang; Thompson, George R; Wong, Joseph K; Dandekar, Satya

    2017-05-02

    Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4 + T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4 + T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4 + T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy. IMPORTANCE Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and

  17. Immigration and viral hepatitis

    OpenAIRE

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J.; Janssen, Harry

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly or...

  18. Understanding Image Virality

    Science.gov (United States)

    2015-06-08

    of images that is most similar to ours is the concurrently introduced viral meme generator of Wang et al., that combines NLP and Computer Vision (low...from what we might expect at a first glance. An analogous scenario researched in NLP is understanding the semantics of “That’s what she said!” jokes...and will require NLP and Computer Vision for understanding. 4.1. Intrinsic context We first examine whether humans and machines can pre- dict just by

  19. Viral disorder or disordered viruses: do viral proteins possess unique features?

    Science.gov (United States)

    Xue, Bin; Williams, Robert W; Oldfield, Christopher J; Goh, Gerard Kian-Meng; Dunker, A K; Uversky, Vladimir N

    2010-08-01

    Many proteins or their regions are disordered in their native, biologically active states. Bioinformatics has revealed that these proteins/regions are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition, signal transduction, protein-protein, and protein-nucleic acid interactions. Viruses, these "organisms at the edge of life", have uniquely evolved to be highly adaptive for fast change in their biological and physical environment. To sustain these fast environmental changes, viral proteins elaborated multiple measures, from relatively low van der Waals contact densities, to inclusion of a large fraction of residues that are not arranged in well-defined secondary structural elements, to heavy use of short disordered regions, and to high resistance to mutations. On the other hand, viral proteins are rich in intrinsic disorder. Some of the intrinsically disordered regions are heavily used in the functioning of viral proteins. Others likely have evolved to help viruses accommodate to their hostile habitats. Still others evolved to help viruses in managing their economic usage of genetic material via alternative splicing, overlapping genes, and anti-sense transcription. In this review, we focus on structural peculiarities of viral proteins and on the role of intrinsic disorder in their functions.

  20. Suppression in simultaneous masking.

    Science.gov (United States)

    Fastl, H; Bechly, M

    1983-09-01

    Suppression, i.e., the decrease of masked threshold caused by the addition of a second masker M2 to a first masker M1, is measured for the case of simultaneous masking. The magnitude of suppression decreases with increasing test tone duration; pulsed maskers elicit somewhat more suppression than continuous maskers. In comparison to suppression effects obtained in nonsimultaneous masking (post-masking, pulsation threshold) suppression in simultaneous masking is considerably smaller and was found only at the lower slopes of the two maskers. Suppression in simultaneous masking would not be predicted by those models of suppression which require nonsimultaneous presentation of maskers and test sound.

  1. Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

    Science.gov (United States)

    Hu, Yanqing; Havlin, Shlomo; Makse, Hernán A.

    2014-04-01

    A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up "new ideas." Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through "viral" influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden "influence links." Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

  2. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  3. Equine viral arteritis

    Directory of Open Access Journals (Sweden)

    Kosec Marjan

    2016-01-01

    Full Text Available Equine viral arteritis (EVA is a contagious disease of equids caused by equine artheritis virus (EAV, widespread in most countries in the world, where patients are diagnosed. The infection usually starts asymptomatic. Clinical signs indicate respiratory infection of different intensity and also abortions are present at different stages of gestation. Large prevalence of this disease in the world has become a growing economic problem. The disease is specific to a particular kind of animals, and it affects only equids (horses, donkeys, mules, mule and zebras. In countries where the infection has been confirmed, the percentage of positive animals differ. Likewise, there is difference in percentage among certain animal kinds. The highest percentage of positive animals has been found in totters and the lowest in cold-blooded.

  4. Viral gene therapy.

    Science.gov (United States)

    Mancheño-Corvo, P; Martín-Duque, P

    2006-12-01

    Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

  5. Mycoviruses, RNA silencing, and viral RNA recombination.

    Science.gov (United States)

    Nuss, Donald L

    2011-01-01

    In contrast to viruses of plants and animals, viruses of fungi, mycoviruses, uniformly lack an extracellular phase to their replication cycle. The persistent, intracellular nature of the mycovirus life cycle presents technical challenges to experimental design. However, these properties, coupled with the relative simplicity and evolutionary position of the fungal host, also provide opportunities for examining fundamental aspects of virus-host interactions from a perspective that is quite different from that pertaining for most plant and animal virus infections. This chapter presents support for this view by describing recent advances in the understanding of antiviral defense responses against one group of mycoviruses for which many of the technical experimental challenges have been overcome, the hypoviruses responsible for hypovirulence of the chestnut blight fungus Cryphonectria parasitica. The findings reveal new insights into the induction and suppression of RNA silencing as an antiviral defense response and an unexpected role for RNA silencing in viral RNA recombination. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. VIRAL DISEASES IN SEA FISH

    Directory of Open Access Journals (Sweden)

    Ivančica Strunjak-Perović

    1996-12-01

    Full Text Available Adequate knowledge on fish diseases caused by viruses is still lacking. Up until now, in fish which live their entire life cycle or part of it in the sea, some viral diseases have been determined (lymphoeytis, viral necrosis of crythrocytes, ciravosti cod syndrome, encephalitis, viral hemoragic septichemistry, viral hematopoetic necrosis, viral gusteraca necrosis, chum renviral infection, branchionephritis, rabdociral eel infection. Some of these diseases primarily occur in the freshwater phase of host development, although recordings exist that the virus is carried on in surving samples which succeed in making it to the sea. As the number of sea fish species increases in controlled culture a increasing number of pathological cases are observed, which is caused by viruses. Therefore, in this area it is necessary to emphasize future investigations.

  7. Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features.

    Science.gov (United States)

    Tamilzhalagan, Sembulingam; Rathinam, Dhanasekaran; Ganesan, Kumaresan

    2017-06-01

    Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7, and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 and MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors. Across gastric tumors, miR-25 was identified to co-express with MCM7 and SHFM1. On the other hand, negative correlation was observed between miR-25 and COL1A2 expression. miR-25 originating from MCM7 was found capable of selectively targeting the adjacent gene COL1A2. Silencing of miR-25 was found capable of elevating the expression of COL1A2 and inhibiting E-cadherin expression, revealing the diffuse type gastric cancer suppressive role conferred by miR-25. miR-25 was also found to suppress p53, and activate c-Src revealing its intestinal type gastric cancer associated oncogenic functions. Genome-wide expression profiling upon miR-25 silencing reveals that miR-25 is capable of suppressing 40 genes which are co-expressed with COL1A2, involved in epithelial to mesenchymal transition and angiogenesis which are the typical diffuse type gastric cancer features. The results clearly demonstrate 7q21-22 amplification, MCM7, and its intronic miR-25 are the major molecular switches involved in the complex oncogenic circuits of gastric cancer. © 2017 Wiley Periodicals, Inc.

  8. Anti-viral RNA silencing: do we look like plants ?

    Directory of Open Access Journals (Sweden)

    Lecellier Charles-Henri

    2006-01-01

    Full Text Available Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(miRNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (siRNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.

  9. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  10. Growth hormone suppression test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  11. Insulated Foamy Viral Vectors

    Science.gov (United States)

    Browning, Diana L.; Collins, Casey P.; Hocum, Jonah D.; Leap, David J.; Rae, Dustin T.; Trobridge, Grant D.

    2016-01-01

    Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34+ cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

  12. Tight Junctions Go Viral!

    Directory of Open Access Journals (Sweden)

    Jesús M. Torres-Flores

    2015-09-01

    Full Text Available Tight junctions (TJs are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.

  13. Viral Hepatitis: A through E and Beyond

    Science.gov (United States)

    Viral Hepatitis: A through E and Beyond NATIONAL INSTITUTES OF HEALTH U.S. Department of Health and Human Services National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused ...

  14. Viral infections as controlling factors for the deep biosphere? (Invited)

    Science.gov (United States)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    biogeography? Can viral infections tell us something about the physiological state of indigenous microorganisms? Finally, we will obtain estimates for the viral shunt as an important factor for sustaining the deep biosphere. References: Batzke A, Engelen B, Sass H, Cypionka H (2007) Phylogenetic and physiological diversity of cultured deep-biosphere bacteria from Equatorial Pacific Ocean and Peru Margin sediments. Geomicrobiology J 24:261-273 Danovaro R, Dell'Anno A, Corinaldesi C, Magagnini M, Noble R, Tamburini C, Weinbauer M (2008) Major viral impact on the functioning of benthic deep-sea ecosystems. Nature 454: 1084-U1027.

  15. Sustainable agriculture

    National Research Council Canada - National Science Library

    Lichtfouse, Eric

    2009-01-01

    ... : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 Part I CLIMATE CHANGE Soils and Sustainable Agriculture: A Review : : : : : : : : : : : : : : : : : : : : : : : : : : Rattan Lal 15 Soils and Food Sufficiency...

  16. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  17. Defining the chemokine basis for leukocyte recruitment during viral encephalitis.

    Science.gov (United States)

    Michlmayr, Daniela; McKimmie, Clive S; Pingen, Marieke; Haxton, Ben; Mansfield, Karen; Johnson, Nicholas; Fooks, Anthony R; Graham, Gerard J

    2014-09-01

    The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of

  18. Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

    Directory of Open Access Journals (Sweden)

    Yanqing Hu

    2014-05-01

    Full Text Available A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up “new ideas.” Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through “viral” influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden “influence links.” Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

  19. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  20. Viral marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and simulations using the Matlab software are performed. Finally, some conclusions are given and their marketing impli...

  1. FastStats: Viral Hepatitis

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,239 (2014) Number of new ...

  2. Aseptic meningitis and viral myelitis.

    Science.gov (United States)

    Irani, David N

    2008-08-01

    Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

  3. Viral Evolution Core | FNLCR Staging

    Science.gov (United States)

    Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

  4. Viral hepatitis in minority America.

    Science.gov (United States)

    Rawls, Renard A; Vega, Kenneth J

    2005-02-01

    Viral hepatitis continues as an important public health concern in the United States. Available data indicate that acute and chronic viral hepatitis remains an important cause of morbidity and mortality in this country despite the availability of immunization for hepatitis A and B and pharmacologic therapy for chronic hepatitis B and C. Minority populations within the United States are disproportionately affected by acute and chronic viral hepatitis. Many diseases, for example, Barrett's esophagus, affect ethnic groups differently. Viral hepatitis A, B, and C may demonstrate ethnic variation with regard to their epidemiology, natural history, clinicopatholgic findings, complications, and treatment outcomes. This report will review the literature regarding these areas in hepatitis A, B, and C among the African American, Hispanic American, and Native American populations of the United States.

  5. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  6. Rhizosphere Microbiome Recruited from a Suppressive Compost Improves Plant Fitness and Increases Protection against Vascular Wilt Pathogens of Tomato

    NARCIS (Netherlands)

    Antoniou, Anastasis; Tsolakidou, Maria; Stringlis, I.|info:eu-repo/dai/nl/41185206X; Pantelides, Iakovos

    2017-01-01

    Suppressive composts represent a sustainable approach to combat soilborne plant pathogens and an alternative to the ineffective chemical fungicides used against those. Nevertheless, suppressiveness to plant pathogens and reliability of composts are often inconsistent with unpredictable effects.

  7. Viral replication rate regulates clinical outcome and CD8 T cell responses during highly pathogenic H5N1 influenza virus infection in mice.

    Directory of Open Access Journals (Sweden)

    Yasuko Hatta

    2010-10-01

    Full Text Available Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans.

  8. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  9. [Neuropsychiatric sequelae of viral meningitis in adults].

    Science.gov (United States)

    Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

    2011-10-10

    Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

  10. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  11. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  12. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

  13. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution. © 2013 médecine/sciences – Inserm.

  14. Fatal neurological respiratory insufficiency is common among viral encephalitides.

    Science.gov (United States)

    Wang, Hong; Siddharthan, Venkatraman; Kesler, Kyle K; Hall, Jeffery O; Motter, Neil E; Julander, Justin G; Morrey, John D

    2013-08-15

    Neurological respiratory insufficiency strongly correlates with mortality among rodents infected with West Nile virus (WNV), which suggests that this is a primary mechanism of death in rodents and possibly fatal West Nile neurological disease in human patients. To explore the possibility that neurological respiratory insufficiency is a broad mechanism of death in cases of viral encephalitis, plethysmography was evaluated in mice infected with 3 flaviviruses and 2 alphaviruses. Pathology was investigated by challenging the diaphragm, using electromyography with hypercapnia and optogenetic photoactivation. Among infections due to all but 1 alphavirus, death was strongly associated with a suppressed minute volume. Virally infected mice with a very low minute volume did not neurologically respond to hypercapnia or optogenetic photoactivation of the C4 cervical cord. Neurons with the orexin 1 receptor protein in the ventral C3-5 cervical cord were statistically diminished in WNV-infected mice with a low minute volume as compared to WNV-infected or sham-infected mice without respiratory insufficiency. Also, WNV-infected cells were adjacent to neurons with respiratory functions in the medulla. Detection of a common neurological mechanism of death among viral encephalitides creates opportunities to create broad-spectrum therapies that target relevant neurological cells in patients with types of viral encephalitis that have not been treatable in the past.

  15. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted...... variations at glycosylation sites. In conclusion, the viral O-glycosyl peptide epitopes may be of relevance for development of subunit vaccines and for improved serodiagnosis of viral diseases. Copyright © 2015 John Wiley & Sons, Ltd....

  16. Factors associated with time to achieve an undetectable HIV RNA viral load after start of antiretroviral treatment in HIV-1-infected pregnant women

    NARCIS (Netherlands)

    Snippenburg, W.; Nellen, F. J. B.; Smit, C.; Wensing, A. M. J.; Godfried, M. H.; Mudrikova, T.

    2017-01-01

    To identify factors associated with the time to viral suppression in women starting antiretroviral treatment (ART) during pregnancy. Knowledge on duration of viral load (VL) decline could help deciding the timing of treatment initiation. Highly active antiretroviral treatment (HAART)-naive pregnant

  17. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...

  18. Sustaining dairy

    NARCIS (Netherlands)

    Villarreal Herrera, Georgina

    2017-01-01

    Dairy in Europe has undergone many changes in the last few years—the abolition of milk production quotas being a fundamental one. This study explores these changes in relation to the sustained social and environmental viability of the sector and how dairy processors' sustainability

  19. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    . Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...... campus performance....

  20. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  1. Sustainable Learning

    Science.gov (United States)

    Cadwell, Louise; Dillon, Robert

    2011-01-01

    Green schools have moved into a new era that focuses on building a culture of sustainability in every aspect of learning in schools. In the early stages of sustainability education, the focus was on recycling and turning off the lights. Now, students and adults together are moving into the areas of advocacy and action that are based on a deep…

  2. Viral escape in the CNS with multidrug-resistant HIV-1

    Directory of Open Access Journals (Sweden)

    Charles Béguelin

    2014-11-01

    Full Text Available Introduction: HIV-1 viral escape in the cerebrospinal fluid (CSF despite viral suppression in plasma is rare [1,2]. We describe the case of a 50-year-old HIV-1 infected patient who was diagnosed with HIV-1 in 1995. Antiretroviral therapy (ART was started in 1998 with a CD4 T cell count of 71 cells/ìL and HIV-viremia of 46,000 copies/mL. ART with zidovudine (AZT, lamivudine (3TC and efavirenz achieved full viral suppression. After the patient had interrupted ART for two years, treatment was re-introduced with tenofovir (TDF, emtricitabin (FTC and ritonavir boosted atazanavir (ATVr. This regimen suppressed HIV-1 in plasma for nine years and CD4 cells stabilized around 600 cells/ìL. Since July 2013, the patient complained about severe gait ataxia and decreased concentration. Materials and Methods: Additionally to a neurological examination, two lumbar punctures, a cerebral MRI and a neuropsycological test were performed. HIV-1 viral load in plasma and in CSF was quantified using Cobas TaqMan HIV-1 version 2.0 (Cobas Ampliprep, Roche diagnostic, Basel, Switzerland with a detection limit of 20 copies/mL. Drug resistance mutations in HIV-1 reverse transcriptase and protease were evaluated using bulk sequencing. Results: The CSF in January 2014 showed a pleocytosis with 75 cells/ìL (100% mononuclear and 1,184 HIV-1 RNA copies/mL, while HIV-1 in plasma was below 20 copies/mL. The resistance testing of the CSF-HIV-1 RNA showed two NRTI resistance-associated mutations (M184V and K65R and one NNRTI resistance-associated mutation (K103N. The cerebral MRI showed increased signal on T2-weighted images in the subcortical and periventricular white matter, in the basal ganglia and thalamus. Four months after ART intensification with AZT, 3TC, boosted darunavir and raltegravir, the pleocytosis in CSF cell count normalized to 1 cell/ìL and HIV viral load was suppressed. The neurological symptoms improved; however, equilibrium disturbances and impaired memory

  3. Viral diseases affecting the pleura.

    Science.gov (United States)

    Nestor, Jennings; Huggins, Terrill; Kummerfeldt, Carlos; DiVietro, Matthew; Walters, Kenneth; Sahn, Steven

    2013-10-01

    Viruses affect the human body in multiple ways producing various disease states. The infections of the pulmonary parenchyma have been well described. However, there has been no current review of the literature pertaining to the pleura. To review the available literature pertaining to diseases of the pleura that are caused by viral infections. A Medline search was performed and available research and review articles relating to viral infections that resulted in pleural effusions, pleural masses, pleural thickening, and pleural nodularity were reviewed. There are numerous viruses that cause diseases of the pleura. Pleural effusions and lesions within the pleura are the most common presentation of the disease state. Polymerase chain reaction has the potential to further diagnose viral infections and expand our knowledge base in this field. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Acute bacterial and viral meningitis.

    Science.gov (United States)

    Bartt, Russell

    2012-12-01

    Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

  5. Viral Infections and Febrile Seizures

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-01-01

    Full Text Available The incidence of febrile seizures (FS in a cohort of children, ages 3 months to 5 years, living in a Netherlands province was compared with the incidence of common viral infections reported to a national registry and the results reported from the Department of Medical Microbiology, Public Health Laboratory Friesland, Leeuwarden, The Netherlands.

  6. Viral Infection and Hepatocellular Carcinoma

    NARCIS (Netherlands)

    J. Li (Juan)

    2017-01-01

    markdownabstractMuch of liver pathology is related to infection with HBV and HCV and it is important to define factors associated with clinical behavior of disease following infection with these viruses. Thus in this thesis I first focus on the natural history of chronic viral diseases associated

  7. Viral hepatitis B- an overview

    African Journals Online (AJOL)

    1994-08-08

    Aug 8, 1994 ... Hepatitis B e antigen. (HBeAg) is a soluble non-structural, enigmatic antigen which is often detected in the blood of patients infected with replicating HBV which results in massive viral load in the blood. Both HBe and HBc are derived from the same section of HBV DNA but the HBe transcript contains an.

  8. Effects of chloroquine on viral infections: an old drug against today's diseases?

    Science.gov (United States)

    Savarino, Andrea; Boelaert, Johan R; Cassone, Antonio; Majori, Giancarlo; Cauda, Roberto

    2003-11-01

    Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.

  9. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  10. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  11. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  12. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003......), urban design competitions are understudied mechanisms for bringing about field level changes. Drawing on actor network theory, this paper examines how urban design competitions may bring about changes within the professional field through the use of intermediaries such as a sustainable planning....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  13. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  14. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  15. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  16. Autistic disorder and viral infections.

    Science.gov (United States)

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

  17. Sustainable finance

    OpenAIRE

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence Sustainable Business Administration & Management Accounting, Financial Leadership and what is the importance of CSR in the financial sector

  18. Anti-viral treatment and cancer control.

    Science.gov (United States)

    Shih, Wei-Liang; Fang, Chi-Tai; Chen, Pei-Jer

    2014-01-01

    Hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV) contribute to about 10-15 % global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infections have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell lymphotropic virus type 1 (HTLV-1) had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA-interference-based therapies for treating HPV-associated cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

  19. SUSTAINABLE TRANSPORTATION

    Directory of Open Access Journals (Sweden)

    Linda STEG

    2007-01-01

    Full Text Available This paper discusses possible contributions of psychologists to sustainable transportation. It is argued that in order to reach sustainable transportation, among others, behaviour changes of individual car users are needed. As transport policies will be more effective if they target important antecedents of travel behaviour, first, factors influencing such behaviour are discussed. It is argued that car use is very attractive and sometimes even necessary for many different reasons. This implies that a combination of policies is called for, each targeting different factors that support car use and hinder the use of more sustainable modes of transport. Next, the paper elaborates on policy strategies that may be employed to achieve sustainable transportation by changing car use. Increasing the attractiveness of sustainable transport modes by means of pull measures seems not sufficient to reduce the level of car use. Besides, car use should be made less attractive by means of push measures to force drivers to reconsider their travel behaviour. The acceptability of such policies may be increased by clearly communicating the aim of these policies, and the expected positive consequences (e.g., less congestion, improved environmental quality. Moreover, possible negative effects for individual freedom may be compensated by implementing additional policies aimed at facilitating the use of sustainable transport modes.

  20. My Cousin, My Enemy: quasispecies suppression of drug resistance

    Science.gov (United States)

    Kirkegaard, Karla; van Buuren, Nicholas J; Mateo, Roberto

    2017-01-01

    If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny’s growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for ‘dominant drug targeting’ as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus. Small molecules that stabilize oligomeric assemblages are a promising means to an unfit family to destroy the effectiveness of a newborn drug-resistant relative due to the co-assembly of drug-susceptible and drug-resistant monomers. PMID:27764731

  1. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  2. Menstrual suppression for adolescents.

    Science.gov (United States)

    Altshuler, Anna Lea; Hillard, Paula J Adams

    2014-10-01

    The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management. Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions. This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful.

  3. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Robert Y.L., E-mail: yuwang@mail.cgu.edu.tw [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Kuo, Rei-Lin [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Ma, Wei-Chieh [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Hsing-I [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yu, Jau-Song [Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yen, Sih-Min [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Chi-Ruei [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Shih, Shin-Ru [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China)

    2013-09-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone. - Highlights: • Hsp90β is associated with EV71 virion and is secreted with the release virus. • Hsp90β effects on the correct assembly of viral particles. • Viral titer of cultured medium was reduced in the presence of geldanamycin. • Viral titer was also reduced when Hsp90β was suppressed by siRNA treatment. • The extracellular Hsp90β was also observed in other RNA viruses-infected cells.

  4. Non-random patterns in viral diversity

    DEFF Research Database (Denmark)

    Anthony, Simon J.; Islam, Ariful; Johnson, Christine

    2015-01-01

    It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stocha...

  5. Faktor Risiko Non Viral Pada Karsinoma Nasofaring

    Directory of Open Access Journals (Sweden)

    Sukri Rahman

    2015-09-01

    Full Text Available Abstrak           Latar belakang: Karsinoma nasofaring adalah tumor ganas epitel nasofaring yang sampai saat ini penyebabnya belum diketahui, infeksi virus Epstein Barr dilaporkan sebagai faktor dominan terjadinya karsinoma nasofaring tetapi faktor non viral juga berperan untuk timbulnya keganasan nasofaring. Tujuan: Untuk mengetahui faktor non viral  yang dapat meningkatkan kejadian karsinoma nasofaring sehingga dapat mencegah dan menghindari faktor-faktor non viral tersebut. Tinjauan Pustaka: Karsinoma nasofaring merupakan tumor ganas epitel nasofaring yang penyebabnya berhubungan dengan faktor viral dan non viral diantaranya asap rokok, ikan asin, formaldehid, genetik, asap kayu bakar , debu kayu, infeksi kronik telinga hidung tenggorok, alkohol dan obat tradisional. Kesimpulan: Pembuktian secara klinis dan ilmiah terhadap faktor non viral sebagai penyebab timbulnya karsinoma nasofaring masih belum dapat dijelaskan secara pasti. Faktor non viral merupakan salah satu faktor risiko yang dapat meningkatkan angka kejadian timbulnya keganasan nasofaring Kata kunci: karsinoma nasofaring, faktor risiko, non viral AbstractBackground: Nasopharyngeal carcinoma is a malignant epithelial nasopharyngeal tumor that until now the cause still unknown, Epstein barr virus infection had reported as predominant occurance of nasopharyngeal carcinoma but non viral factors may also contribute to the onset of the incidence of nasopharyngeal malignancy. Purpose: To find non viral factors that may increase the incidence of nasopharyngel carcinoma in order to prevent and avoid non-viral factors Literature: Nasopharyngeal carcinoma is a malignant tumor that causes nasopharyngeal epithelium associated with viral and non-viral factors such as cigarette smoke, salt fish, formaldehyde, genetic, wood smoke ,wood dust, ear nose throat chronic infections, alcohol, and traditional medicine. Conclusion: Clinically and scientifically proving the non-viral factors as

  6. Mechanisms of influenza viral membrane fusion

    NARCIS (Netherlands)

    Blijleven, Jelle S; Boonstra, Sander; Onck, Patrick R; van der Giessen, Erik; van Oijen, Antoine M

    2016-01-01

    Influenza viral particles are enveloped by a lipid bilayer. A major step in infection is fusion of the viral and host cellular membranes, a process with large kinetic barriers. Influenza membrane fusion is catalyzed by hemagglutinin (HA), a class I viral fusion protein activated by low pH. The exact

  7. Viral commercials: the consumer as marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  8. Virale commercials: De consument als marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

  9. Viral ecology of a shallow eutrophic lake

    NARCIS (Netherlands)

    Tijdens, M.

    2007-01-01

    This thesis aims to give an insight into the ecology of the viral community in a shallow eutrophic lake. To achieve this, the population dynamics, diversity and control of the viral community in Lake Loosdrecht were studied, as well as the impact of the viral community on plankton mortality and

  10. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  11. Progress realized: trends in HIV-1 viral load and CD4 cell count in a tertiary-care center from 1999 through 2011.

    Directory of Open Access Journals (Sweden)

    Howard B Gale

    Full Text Available HIV-1 RNA and CD4 cell counts are important parameters for HIV care. The objective of this study was to assess the overall trends in HIV-1 viral load and CD4 cell counts within our clinic.Patients with at least one of each test performed by the Infectious Diseases Laboratory from 1999 through 2011 were included in this analysis. By adapting a novel statistical model, log(10 HIV-1 RNA means were estimated by month, and log(10-transformed HIV-1 RNA means were estimated by calendar year. Geometric means were calculated for CD4 cell counts by month and calendar year. Log(10 HIV-1 RNA and CD4 cell count monthly means were also examined with polynomial regression.There were 1,814 individuals with approximately 25,000 paired tests over the 13-year observation period. Based on each patient's final value of the year, the percentage of patients with viral loads below the lower limit of quantitation rose from 29% in 1999 to 72% in 2011, while the percentage with CD4 counts <200 cells/µL fell from 31% to 11%. On average annually, the mean HIV-1 RNA decreased by 86 copies/mL and the mean CD4 counts increased by 16 cells/µL. For the monthly means, the correlations (R(2 from second-order polynomial regressions were 0.944 for log(10 HIV-1 RNA and 0.840 for CD4 cell counts.Marked improvements in HIV-1 RNA suppression and CD4 cell counts were achieved in a large inner-city population from 1999 through 2011. This success demonstrates that sustained viral control with improved immunologic status can be a realistic goal for most individuals in clinical care.

  12. APLASTIC ANEMIA AND VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    Laura Cudillo

    2009-11-01

    Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic  and blood lymphocytes with  T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia.

  13. Treatment of Acute Viral Bronchiolitis

    Science.gov (United States)

    Eber, Ernst

    2011-01-01

    Acute viral bronchiolitis represents the most common lower respiratory tract infection in infants and young children and is associated with substantial morbidity and mortality. Respiratory syncytial virus is the most frequently identified virus, but many other viruses may also cause acute bronchiolitis. There is no common definition of acute viral bronchiolitis used internationally, and this may explain part of the confusion in the literature. Most children with bronchiolitis have a self limiting mild disease and can be safely managed at home with careful attention to feeding and respiratory status. Criteria for referral and admission vary between hospitals as do clinical practice in the management of acute viral bronchiolitis, and there is confusion and lack of evidence over the best treatment for this condition. Supportive care, including administration of oxygen and fluids, is the cornerstone of current treatment. The majority of infants and children with bronchiolitis do not require specific measures. Bronchodilators should not be routinely used in the management of acute viral bronchiolitis, but may be effective in some patients. Most of the commonly used management modalities have not been shown to have a clear beneficial effect on the course of the disease. For example, inhaled and systemic corticosteroids, leukotriene receptor antagonists, immunoglobulins and monoclonal antibodies, antibiotics, antiviral therapy, and chest physiotherapy should not be used routinely in the management of bronchiolitis. The potential effect of hypertonic saline on the course of the acute disease is promising, but further studies are required. In critically ill children with bronchiolitis, today there is little justification for the use of surfactant and heliox. Nasal continuous positive airway pressure may be beneficial in children with severe bronchiolitis but a large trial is needed to determine its value. Finally, very little is known on the effect of the various

  14. Viral exanthems in the tropics.

    Science.gov (United States)

    Carneiro, Sueli Coelho da Silva; Cestari, Tania; Allen, Samuel H; Ramos e-Silva, Marcia

    2007-01-01

    Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; Lassa fever; and South American hemorrhagic fevers will be discussed.

  15. Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation.

    OpenAIRE

    Stoler, A; Bouck, N

    1985-01-01

    Normal human fibroblasts were fused to carcinogen-transformed baby hamster kidney (BHK) cells and found to be able to suppress the anchorage-independent transformed phenotype of the hamster cells. This suppression was not due to interspecies incompatibility, for transformation could be effectively expressed in hybrids if either the human or the BHK parent had initially been transformed by a dominantly acting viral genome. Upon growth of suppressed hybrids, loss of human chromosomes was accomp...

  16. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    The willingness of public authority to delegate social and environmental regulation to the private sector has varied from sector to sector, but has often led to the establishment of ‘voluntary’ standards and certifications on sustainability. Many of these have taken the form of ‘stewardship...... councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity......-specific sustainability situations into a form that not only ‘hears more voices’ (as in ‘multi-stakeholder’), but also portrays to give them equal standing at the table of negotiations (roundtable), thus raising higher expectations on accountability, transparency and inclusiveness. In this article, I examine to what...

  17. Recycling Endosomes and Viral Infection

    Directory of Open Access Journals (Sweden)

    Sílvia Vale-Costa

    2016-03-01

    Full Text Available Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC, and mediated by its regulatory Ras-related in brain (Rab GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  18. Maternal immunization against viral disease.

    Science.gov (United States)

    Englund, J; Glezen, W P; Piedra, P A

    1998-01-01

    The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to medical care and respond well to vaccines, that IgG antibodies cross the placenta well during the third trimester, and that immunization of the pregnant woman has the potential to benefit both the mother and the infant. Disadvantages include the potential inhibition of an infant's response to active immunization or natural infection and liability issues with pharmaceutical companies and physicians. Immunization of pregnant women with viral vaccines for poliovirus, influenza viruses, and rubella has been described and maternal vaccination with these vaccines has been found to be safe for both the mother and the fetus. An open-label study of post-partum women immunized with the purified fusion protein of RSV (PFP-2, Wyeth-Lederle Pediatrics and Vaccines, Inc., Pearl River, NY) demonstrated that the vaccine was non-reactogenic and immunogenic; RSV-specific antibody was detected in breast milk. Immunization of pregnant women with purified protein or subunit vaccines could be considered against neonatal viral pathogens, such as respiratory syncytial virus, parainfluenza viruses, herpes group viruses, and human immunodeficiency virus. Further studies are needed to define the safety and efficacy of maternal immunization.

  19. Pediatric Asthma and Viral Infection.

    Science.gov (United States)

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

  20. Sustainability Evaluation.

    Science.gov (United States)

    Stichnothe, Heinz

    2017-03-17

    The long-term substitution of fossil resources can only be achieved through a bio-based economy, with biorefineries and bio-based products playing a major role. However, it is important to assess the implications of the transition to a bio-based economy. Life cycle-based sustainability assessment is probably the most suitable approach to quantify impacts and to identify trade-offs at multiple levels. The extended utilisation of biomass can cause land use change and affect food security of the most vulnerable people throughout the world. Although this is mainly a political issue and governments should be responsible, the responsibility is shifted to companies producing biofuels and other bio-based products. Organic wastes and lignocellulosic biomass are considered to be the preferred feedstock for the production of bio-based products. However, it is unlikely that a bio-based economy can rely only on organic wastes and lignocellulosic biomass.It is crucial to identify potential problems related to socio-economic and environmental issues. Currently there are many approaches to the sustainability of bio-based products, both quantitative and qualitative. However, results of different calculation methods are not necessarily comparable and can cause confusion among decision-makers, stakeholders and the public.Hence, a harmonised, globally agreed approach would be the best solution to secure sustainable biomass/biofuels/bio-based chemicals production and trade, and to avoid indirect effects (e.g. indirect land use change). However, there is still a long way to go.Generally, the selection of suitable indicators that serve the purpose of sustainability assessment is very context-specific. Therefore, it is recommended to use a flexible and modular approach that can be adapted to various purposes. A conceptual model for the selection of sustainability indicators is provided that facilitates identifying suitable sustainability indicators based on relevance and significance in a

  1. Disease Suppressive Soils: New Insights from the Soil Microbiome.

    Science.gov (United States)

    Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

    2017-11-01

    Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

  2. Emerging viral diseases of fish and shrimp

    Science.gov (United States)

    Winton, James R.; Walker, Peter J.

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change.

  3. Viral Hepatitis: Information for Gay and Bisexual Men

    Science.gov (United States)

    VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by ... United States, the most common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. ...

  4. Behavioral and Other Characteristics Associated with HIV Viral Load in an Outpatient Clinic.

    Directory of Open Access Journals (Sweden)

    Paul L Sacamano

    Full Text Available Persons living with HIV (PLWH who are engaged in care, yet not virally suppressed, represent a risk for transmission and opportunity for risk reduction interventions. This study describes characteristics of an outpatient clinic cohort of PLWH by laboratory confirmed viral suppression status and examines associations with demographics and sexual and drug use behaviors gathered through questionnaire. From a sample of 500 clinic patients, 438 were prescribed antiretroviral treatment (ART and 62 were not. Among the 438 on ART, 72 (16.4% were not virally suppressed at the most recent lab draw. Compared to individuals with a suppressed viral load, those that were unsuppressed were more likely to: be black (79.2% vs. 64.2%; p = 0.014; earn below $25,000/year (88.9% vs. 65.0%; p < 0.001; be of a younger age (47.8 vs. 50.0 mean years; p = 0.009; be on opiate substitution (14.1% vs. 6.3%; p = 0.023; and acknowledge poly-substance (38.9% vs. 24.4%; p = 0.012 and excessive alcohol use (13.9% vs. 6.0%; p = 0.019. Conversely, a smaller proportion of those with an unsuppressed viral load had multiple sex partners in the previous 30 days (39.8% vs. 58.5%; p = 0.003. In multivariable regression of those on ART, the prevalence of an unsuppressed viral load was 3% lower with each increasing year of age (aPR: 0.97; 95% CI: 0.95, 0.99 and 47% lower with income over $25,000/year (aPR: 0.33; 95% CI: 0.16, 0.70. In a separate analysis of all 500 subjects, ART was less frequently prescribed to blacks compared to whites, heterosexuals, those with lower education and income, and persons with active substance use. Findings confirm that a large proportion of PLWH and engaged in care were not virally suppressed and continued behaviors that risk transmission, indicating the need for screening, prevention counseling and access to ancillary services to lower the incidence of HIV infections.

  5. Role of PKR and Type I IFNs in viral control during primary and secondary infection.

    Directory of Open Access Journals (Sweden)

    Yumi Nakayama

    2010-06-01

    Full Text Available Type I interferons (IFNs are known to mediate viral control, and also promote survival and expansion of virus-specific CD8+ T cells. However, it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct. One of the best-characterized anti-viral signaling mechanisms of Type I IFNs is mediated by the IFN-inducible dsRNA activated protein kinase, PKR. Here, we have investigated the role of PKR and Type I IFNs in regulating viral clearance and CD8+ T cell response during primary and secondary viral infections. Our studies demonstrate differential requirement for PKR, in viral control versus elicitation of CD8+ T cell responses during primary infection of mice with lymphocytic choriomeningitis virus (LCMV. PKR-deficient mice mounted potent CD8+ T cell responses, but failed to effectively control LCMV. The compromised LCMV control in the absence of PKR was multifactorial, and linked to less effective CD8+ T cell-mediated viral suppression, enhanced viral replication in cells, and lower steady state expression levels of IFN-responsive genes. Moreover, we show that despite normal expansion of memory CD8+ T cells and differentiation into effectors during a secondary response, effective clearance of LCMV but not vaccinia virus required PKR activity in infected cells. In the absence of Type I IFN signaling, secondary effector CD8+ T cells were ineffective in controlling both LCMV and vaccinia virus replication in vivo. These findings provide insight into cellular pathways of Type I IFN actions, and highlight the under-appreciated importance of innate immune mechanisms of viral control during secondary infections, despite the accelerated responses of memory CD8+ T cells. Additionally, the results presented here have furthered our understanding of the immune correlates of anti-viral protective immunity, which have implications in the rational design of vaccines.

  6. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  7. Sustainable agriculture

    International Development Research Centre (IDRC) Digital Library (Canada)

    New farming techniques, better food security. Since 1970, IDRC-supported research has introduced sustainable agricultural practices to farmers and communities across the devel- oping world. The result: higher productivity, less poverty, greater food security, and a healthier environment. Opportunities grow on trees in ...

  8. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Abstract. This article examines the concept of sustainable development after the Post-. 2015 Paris Climate Change Agreement with particular emphasis on Ethiopia. Various African countries are vulnerable to climate change, as is evidenced by recent droughts. Ethiopia is selected as a case study in light of its pace in.

  9. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  10. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  11. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. It The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  12. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  13. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  14. Sustainable finance

    NARCIS (Netherlands)

    dr. Margreet F. Boersma-de Jong

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  15. Explosion suppression system

    Science.gov (United States)

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  16. Encefalitis virales en la infancia

    Directory of Open Access Journals (Sweden)

    Monserrat Téllez de Meneses

    2013-09-01

    Full Text Available La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Muchos de los virus para los cuales existe vacunas también pueden causar encefalitis como: sarampión, paperas, polio, rabia, rubéola, varicela. El virus produce una inflamación del tejido cerebral, la cual puede evolucionar a una destrucción de neuronas, provocar hemorragia y daño cerebral, dando lugar a encefalitis graves, como la encefalitis necrotizante o hemorrágica, con mucho peor pronóstico, produciendo secuelas graves, incluso la muerte. El cuadro clínico, incluye la presencia de cefalea, fiebre y alteración de la conciencia, de rápida progresión. El pronóstico de las encefalitis víricas es variable, algunos casos son leves, con recuperación completa, sin embargo existen casos graves que pueden ocasionar secuelas importantes a nivel cerebral. Es fundamental realizar un diagnóstico lo antes posible, a través de pruebas de laboratorio (bioquímica, PCR, cultivos y de neuroimagen (TAC, RM y ante todo, la instauración de un tratamiento precoz para evitar la evolución del proceso y sus posibles complicaciones. El pronóstico empeora si se retrasa la instauración del tratamiento.

  17. Evaluation of Viral Meningoencephalitis Cases

    Directory of Open Access Journals (Sweden)

    Handan Ilhan

    2012-08-01

    Full Text Available AIM: To evaluate retrospectively adult cases of viral encephalitis. METHOD: Fifteen patients described viral encephalitis hospitalized between the years 2006-2011 follow-up and treatment at the infectious diseases clinic were analyzed retrospectively. RESULTS: Most of the patients (%60 had applied in the spring. Fever (87%, confusion (73%, neck stiffness (73%, headache (73%, nausea-vomiting (33%, loss of consciousness (33%, amnesia (33%, agitation (20%, convulsion (%20, focal neurological signs (13%, Brudzinski-sign (13% were most frequently encountered findings. Electroencephalography test was applied to 13 of 14 patients, and pathological findings compatible with encephalitis have been found. Radiological imaging methods such as CT and MRI were performed in 9 of the 14 patients, and findings consistent with encephalitis were reported. All of initial cerebrospinal fluid (CSF samples were abnormal. The domination of the first examples was lymphocytes in 14 patients; only one patient had an increase in neutrophilic cells have been found. CSF protein level was high in nine patients, and low glucose level was detected in two patients. Herpes simplex virus polymerized chain reaction (PCR analyze was performed to fourteen patients CSF. Only two of them (14% were found positive. One of the patients sample selectively examined was found to be Parvovirus B19 (+, the other patient urine sample Jacobs-creutzfeld virus PCR was found to be positively. Empiric acyclovir therapy was given to all patients. Neuropsychiatric squeal developed at the one patient. CONCLUSION: The cases in the forefront of change in mental status viral meningoencephalitis should be considered and empirical treatment with acyclovir should be started. [TAF Prev Med Bull 2012; 11(4.000: 447-452

  18. SUSTAINABLE CORPORATE AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2017-06-01

    Full Text Available In recent decades, the image of the international business environment has changed significantly. Studies conducted by UNCTAD shows that corporate phenomenon developments in the world economy is growing. Without claiming to present an exhaustive topic so vast we tried to capture some "facets" of sustainable development from the perspective of multinational corporations, given the expansion of these economic entities and strengthening their power in the global economy. We present more negative aspects of the actions of multinational corporations in terms of sustainable development, it is very important to know both sides of the coin, which will not only help transnational giants including release. Based on issues such as corporate social responsibility, environmental pollution and workers' rights, we sought to counter official statements. The conclusion is that these economic entities are real forces that can not be ignored in today's world and the obvious problem of sustainable development can not be addressed independently of the phenomenon, context we also identified some possible solutions to conflict of corporations and essence of the concept of sustainable development.

  19. Non-Viral Deoxyribonucleoside Kinases

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Munch-Petersen, Birgitte; Knecht, Wolfgang

    2015-01-01

    to be valuable in studying the evolution of enzymes. Some of these newly discovered enzymes have been useful in numerous practical applications in medicine and biotechnology, and have contributed to our understanding of the structural basis of nucleoside and nucleoside analogue activation....... of great medical interest. However, during the last 20 years, research on dNKs has gone into non-mammalian organisms. In this review, we focus on non-viral dNKs, in particular their diversity and their practical applications. The diversity of this enzyme family in different organisms has proven...

  20. Immunologic, virologic, and clinical consequences of episodes of transient viremia during suppressive combination antiretroviral therapy

    NARCIS (Netherlands)

    van Sighem, Ard; Zhang, Shuangjie; Reiss, Peter; Gras, Luuk; van der Ende, Marchina; Kroon, Frank; Prins, Jan; de Wolf, Frank

    2008-01-01

    OBJECTIVE: To investigate immunologic, virologic, and clinical consequences of episodes of transient viremia in patients with sustained virologic suppression. METHODS: From the AIDS Therapy Evaluation Project, Netherlands cohort, 4447 previously therapy-naive patients were selected who were on

  1. Seeding method and rate influence on weed suppression in aerobic ...

    African Journals Online (AJOL)

    High weed pressure is amongst the major constraints to the extensive adoption of aerobic rice system as a water-wise technique. Towards developing a sustainable weed management strategy, seeding method and rate may substantially contribute to weed suppression and reduce herbicide use and weeding cost. A trough ...

  2. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...... biophysical, distributional and economic conditions for high consumption in rich countries and then zooms in on the coevolution of provision systems and consumption, and how consumption is shaped by practices and projects in everyday life. Furthermore, the paper discusses whether and how transition...

  3. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems that ...... that need urgent action. The built environment is an obvious area to put effort into because of the large and cost-effective energy saving potential and potential for Renewable Energy-based supply systems for buildings.......The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  4. Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers

    Science.gov (United States)

    Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

    2017-01-01

    Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators. PMID

  5. Viral organization of human proteins.

    Directory of Open Access Journals (Sweden)

    Stefan Wuchty

    2010-08-01

    Full Text Available Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus.

  6. Sequencing Needs for Viral Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  7. Evasion of antiviral immunity through sequestering of TBK1/IKKε/IRF3 into viral inclusion bodies.

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Qu, Bingqian; Zhang, Zerui; Liang, Mifang; Li, Chuan; Cardona, Carol J; Li, Dexin; Xing, Zheng

    2014-03-01

    Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity.

  8. Evasion of Antiviral Immunity through Sequestering of TBK1/IKKε/IRF3 into Viral Inclusion Bodies

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Qu, Bingqian; Zhang, Zerui; Liang, Mifang; Li, Chuan; Cardona, Carol J.; Li, Dexin

    2014-01-01

    Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the Bunyaviridae. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity. PMID:24335286

  9. Virion-targeted viral inactivation: new therapy against viral infection.

    Science.gov (United States)

    Okui, N; Kitamura, Y; Kobayashi, N; Sakuma, R; Ishikawa, T; Kitamura, T

    2001-01-01

    Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of

  10. Design and implementation of an external quality assessment program for HIV viral load measurements using dried blood spots.

    Science.gov (United States)

    Prach, Lisa M; Puren, Adrian; Lippman, Sheri A; Carmona, Sergio; Stephenson, Sophie; Cutler, Ewalde; Barnhart, Scott; Liegler, Teri

    2015-03-01

    An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

    Science.gov (United States)

    Davies, Mary-Ann; Boulle, Andrew; Technau, Karl; Eley, Brian; Moultrie, Harry; Rabie, Helena; Garone, Daniela; Giddy, Janet; Wood, Robin; Egger, Matthias; Keiser, Olivia

    2012-11-01

    To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Analysis of data from children (5000 copies/ml on two consecutive occasions treatment in virologically suppressed children. © 2012 Blackwell Publishing Ltd.

  12. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

    Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  13. Visualizing viral transport and host infection

    Science.gov (United States)

    Son, Kwangmin; Guasto, Jeffrey; Cubillos-Ruiz, Andres; Sullivan, Matthew; Stocker, Roman; MIT Team

    2013-11-01

    A virus is a non-motile infectious agent that can only replicate inside a living host. They consist of a virus-host encounter/adsorption dynamics and subsequently the effectiveness of various tail morphologies for viral infection. Viral transport and the role of viral morphology in host-virus interactions are critical to our understanding of both ecosystem dynamics and human health, as well as to the evolution of virus morphology.

  14. Viral Advertising on Facebook in Vietnam

    OpenAIRE

    Tran, Phuong

    2014-01-01

    The purpose of this thesis is to explore which factors affect the effectiveness of viral advertising on Facebook in Vietnam. The quantitative research method is applied in this research and the sample is Vietnamese Facebook users. After the data analysis stage using SPSS, it became clear that weak ties, perceptual affinity and emotions have an impact on the effectiveness of viral advertising. The results provide a pratical implication of how to make an Ad which can go viral on Facebook. Moreo...

  15. Viral Advertising: Branding Effects from Consumers’ Perspectives

    OpenAIRE

    Jiang, Yueqing

    2012-01-01

    Viral advertising is popular for its high viral transmission results online. Its increased impacts on the social media users have been noticed by the author. At the same time, viewers’ negative attitudes toward traditional advertisements become obvious which can be regarded as the phenomenon of advertisement avoidance. It arouses author’s interests to know how the viral advertising reduces the viewers’ negative emotions and its performances in branding online. This paper is going to look into...

  16. [Workshop on Molecular Epidemiology of Viral Diseases].

    Science.gov (United States)

    Gómez, B; Cabrera, L; Arias, C F

    1997-01-01

    A workshop on viral epidemiology was held on September 29, 1995 at the Medical School of the Universidad Nacional Autónoma de Mexico. The aim of this workshop was to promote interaction among scientists working in viral epidemiology. Eighteen scientists from ten institutions presented their experiences and work. General aspects of the epidemiology of meaningful viral diseases in the country were discussed, and lectures presented on the rota, polio, respiratory syncytial, dengue, papiloma, rabies, VIH and hepatitis viruses.

  17. Viral Subversion of the Nuclear Pore Complex

    Directory of Open Access Journals (Sweden)

    Valerie Le Sage

    2013-08-01

    Full Text Available The nuclear pore complex (NPC acts as a selective barrier between the nucleus and the cytoplasm and is responsible for mediating communication by regulating the transport of RNA and proteins. Numerous viral pathogens have evolved different mechanisms to hijack the NPC in order to regulate trafficking of viral proteins, genomes and even capsids into and out of the nucleus thus promoting virus replication. The present review examines the different strategies and the specific nucleoporins utilized during viral infections as a means of promoting their life cycle and inhibiting host viral defenses.

  18. SUSTAINABLE CHEMISTRY FOR SUSTAINABLE INDUSTRY

    Directory of Open Access Journals (Sweden)

    G. Rizzuto

    2015-01-01

    Full Text Available Foundry Alfe Chem is an industrial reality working in the field of lubrication and chemical auxiliaries for industrial processes, which falls within the framework of the emerging and increasingly important «green chemistry». The goal of the company is to develop products that are more environmentally friendly by using raw materials from renewable sources; specifically, Foundry Alfe Chem has a program of self-sustainability that contemplates, for the foreseeable future, the direct production of renewable raw materials. The company has developed a new dedicated product line, Olitema, whose purpose is to offer highly technological solutions with complete environmental sustainability. In this context, Foundry Alfe CHEM has created a new product which represents a breakthrough in the class of HFC hydraulic fluids: Ecosafe Plus is a biodegradable fire-resistant hydraulic fluid with high engineering and technological performances, high environmental sustainability and the best security guarantees in workplaces. Its formulation is glycols-free, and it allows for easier disposal of the exhausted fluid, compared to a traditional water/ glycol-based HFC hydraulic fluid. For what concern the technological properties, Ecosafe Plus has been tested by accredited laboratories with tribological trials (4 Ball wear test ASTM D 4172, Ball on disc test ASTM 6425, Brugger test DIN 51347, Vickers test ASTM D 2882, with elastomer compatibility test (ASTM D 471 and biodegradability test (OECD 310 F.

  19. Deep molecular characterization of HIV-1 dynamics under suppressive HAART.

    Directory of Open Access Journals (Sweden)

    Maria J Buzón

    2011-10-01

    Full Text Available In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART is required. In this regard, most studies have focused on integrated (proviral HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication-defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse-transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM in order to determine molecular compartmentalization. We observed low molecular variance (mean variability ≤0.042. Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10(-6 AMOVA test; P = 0.001 SM test, suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10(-6 suggesting that episomal and proviral DNA forms originated

  20. Viral diseases of northern ungulates

    Directory of Open Access Journals (Sweden)

    K. Frölich

    2000-03-01

    Full Text Available This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD, alphaherpesvirus infections, malignant catarrhal fever (MCF, poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infection, hog-cholera, Aujeszky's disease and equine herpesvirus infections. There are no significant differences in antibody prevalence to BVDV among deer in habitats with high, intermediate and low density of cattle. In addition, sequence analysis from the BVDV isolated from roe deer (Capreolus capreolus showed that this strain was unique within BVDV group I. Distinct BVDV strains might circulate in free-ranging roe deer populations in Germany and virus transmission may be independent of domestic livestock. Similar results have been obtained in a serological survey of alpha-herpesviruses in deer in Germany. Malignant catarrhal fever was studied in fallow deer (Cervus dama in Germany: the seroprevalence and positive PCR results detected in sheep originating from the same area as the antibody-positive deer might indicate that sheep are the main reservoir animals. Contagious ecthyma (CE is a common disease in domestic sheep and goats caused by the orf virus. CE has been diagnosed in Rocky Mountain bighorn sheep (Ovis canadensis, mountain goats (Oreamnos americanus, Dall sheep (Ovis dalli, chamois (Rupkapra rupi-capra, muskox {Ovibos moschatus and reindeer (Rangifer tarandus. Most parainfluenza type 3 virus infections are mild or clinically undetectable. Serological surveys in wildlife have been successfully conducted in many species. In 1985, a new disease was identified in Swedish moose (Alces alces, designated as Alvsborg disease. This wasting syndrome probably

  1. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...... as subject to substantial regulatory compliance obligations external to the process of procurement. In short, procurement has been transformed in a way to enforce regulatory obligations that are not intrinsic to the process of buying. This leads to the conclusion that questions such as the cost and trade...

  2. Emerging viral diseases of fish and shrimp.

    Science.gov (United States)

    Walker, Peter J; Winton, James R

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. © INRA, EDP Sciences, 2010.

  3. An unexpected twist in viral capsid maturation

    Energy Technology Data Exchange (ETDEWEB)

    Gertsman, Ilya; Gan, Lu; Guttman, Miklos; Lee, Kelly; Speir, Jeffrey A.; Duda, Robert L.; Hendrix, Roger W.; Komives, Elizabeth A.; Johnson, John E.; (Pitt); (Scripps); (UCSD)

    2009-04-14

    Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic

  4. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  5. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  6. Viral Ancestors of Antiviral Systems

    Science.gov (United States)

    Villarreal, Luis P.

    2011-01-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  7. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  8. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  9. Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease

    Directory of Open Access Journals (Sweden)

    Florine E.M. Scholte

    2017-09-01

    Full Text Available Antiviral responses are regulated by conjugation of ubiquitin (Ub and interferon-stimulated gene 15 (ISG15 to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase. We investigated CCHFV OTU function by inactivating protease catalytic activity or by selectively disrupting its deubiquitinase and deISGylase activity using reverse genetics. CCHFV OTU inactivation blocked viral replication independently of its RNA polymerase activity, while deubiquitinase activity proved critical for suppressing the interferon responses. Our findings provide insights into viral OTU functions and support the development of therapeutics and vaccines.

  10. (Npro) protein of bovine viral d

    Indian Academy of Sciences (India)

    Prakash

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle and sheep, and causes significant respiratory and reproductive disease worldwide. Bovine viral diarrhoea virus type 1 (BVDV-1), BVDV-2 along with the border disease virus (BDV) and classical swine fever virus (CSFV) belong to the genus ...

  11. Influence of dendritic cells on viral pathogenicity.

    Science.gov (United States)

    Freer, Giulia; Matteucci, Donatella

    2009-07-01

    Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  12. Influence of dendritic cells on viral pathogenicity.

    Directory of Open Access Journals (Sweden)

    Giulia Freer

    2009-07-01

    Full Text Available Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.

  13. Origins and challenges of viral dark matter.

    Science.gov (United States)

    Krishnamurthy, Siddharth R; Wang, David

    2017-07-15

    The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Type I IFN Signaling Is Dispensable during Secondary Viral Infection.

    Directory of Open Access Journals (Sweden)

    Martin P Hosking

    2016-08-01

    Full Text Available Innate immune responses in general, and type I interferons (T1IFNs in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall response; they are thought (i to be required to drive the early attrition of memory T cells, (ii to support the subsequent expansion of surviving virus-specific memory cells, and (iii to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8+ and CD4+ memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host's immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell's requirement for a cytokine is highly dependent on the cell's maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene's impact by modulating its expression or function in a temporally-controllable manner.

  15. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  16. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  17. Itchy fish and viral dermatopathies: sampling, diagnosis, and management of common viral diseases.

    Science.gov (United States)

    Weber, E P Scott

    2013-09-01

    Viral dermatopathies of fish bear clinical signs similar to those of dermatopathies from other causes. This article offers an overview to approaching dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and management of viral dermatopathies, building on previous publications. It is vital to recognize clinical signs associated with viral dermatopathies because there are currently no treatments available. Avoidance and prevention is the key to controlling viral diseases in fish. Optimizing husbandry practices and providing appropriate quarantine procedures can help prevent viral disease outbreaks in collection and aquaculture stocks. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  19. Natural Killer Cells in Viral HepatitisSummary

    Directory of Open Access Journals (Sweden)

    Barbara Rehermann

    2015-11-01

    Full Text Available Natural killer (NK cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in chronic infection. Here, we review the role of NK cells against hepatitis C virus (HCV and hepatitis B virus (HBV, two agents that cause acute and chronic hepatitis in humans. Interest in NK cells was initially sparked by genetic studies that demonstrated an association between NK cell–related genes and the outcome of HCV infection. Viral hepatitis also provides a model to study the NK cell response to both endogenous and exogenous type I interferon (IFN. Levels of IFN-stimulated genes increase in both acute and chronic HCV infection and pegylated IFNα has been the mainstay of HCV and HBV treatment for decades. In chronic viral hepatitis, NK cells display decreased production of antiviral cytokines. This phenotype is found in both HCV and HBV infection but is induced by different mechanisms. Potent antivirals now provide the opportunity to study the reversibility of the suppressed cytokine production of NK cells in comparison with the antigen-induced defect in IFNγ and tumor necrosis factor-α production of virus-specific T cells. This has implications for immune reconstitution in other conditions of chronic inflammation and immune exhaustion, such as human immunodeficiency virus infection and cancer. Keywords: HBV, HCV, Infection, Interferon, T Cell

  20. Development of Viral Vectors for Gene Therapy for Chronic Pain

    Directory of Open Access Journals (Sweden)

    Yu Huang

    2011-01-01

    Full Text Available Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.

  1. Assembly of viral genomes from metagenomes

    Directory of Open Access Journals (Sweden)

    Saskia L Smits

    2014-12-01

    Full Text Available Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.

  2. Sustainable Scientists

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Evan

    2008-12-31

    Scientists are front and center in quantifying and solving environmental problems. Yet, as a spate of recent news articles in scientific journals point out, much can be done to enhance sustainability within the scientific enterprise itself, particularly by trimming the energy use associated with research facilities and the equipment therein (i,ii,iii, iv). Sponsors of research unwittingly spend on the order of $10 billion each year on energy in the U.S. alone, and the underlying inefficiencies drain funds from the research enterprise while causing 80 MT CO2-equivalent greenhouse-gas emissions (see Box). These are significant sums considering the opportunity costs in terms of the amount of additional research that could be funded and emissions that could be reduced if the underlying energy was used more efficiently. By following commercially proven best practices in facility design and operation, scientists--and the sponsors of science--can cost-effectively halve these costs, while doing their part to put society on alow-carbon diet.

  3. Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.

    Science.gov (United States)

    Zhong, Ting; Zhang, Li-Ying; Wang, Zeng-Yan; Wang, Yue; Song, Feng-Mei; Zhang, Ya-Hong; Yu, Jing-Hua

    2017-03-01

    Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

  4. Vaccines in the Prevention of Viral Pneumonia.

    Science.gov (United States)

    Fraser, Clementine S; Jha, Akhilesh; Openshaw, Peter J M

    2017-03-01

    Pneumonia is of great global public health importance. Viral infections play both direct and indirect parts in its cause across the globe. Influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. Vaccination offers the best prospect for prevention but current influenza vaccines do not provide universal and durable protection, and require yearly reformulation. In the future, it is hoped that influenza vaccines will give better and universal protection, and that new vaccines can be found for other causes of viral pneumonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  6. Sustainable agriculture - selected papers

    OpenAIRE

    Krasowicz, Stanisław; Wrzaszcz, Wioletta; Zegar, Jozef St.

    2007-01-01

    The concept of research on socially sustainable agriculture. Features of sustainable agriculture. Sustainability of private farms in the light of selected criteria. Subsistence agricultural holdings and the sustainable development of agriculture. Sustainable farms in the light of the FADN data. Description of organic holdings in Poland.

  7. Evaluating viral marketing: isolating the key criteria in insurance industry

    National Research Council Canada - National Science Library

    Maria Gooyandeh Hagh

    2015-01-01

    This paper presents an empirical investigation to determine the key criteria that viral marketing practitioners believe should be implemented to measure about the success of viral marketing campaigns...

  8. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  9. The suppression of apoptosis by α-herpesvirus

    Science.gov (United States)

    You, Yu; Cheng, An-Chun; Wang, Ming-Shu; Jia, Ren-Yong; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Zhu, Dekang; Chen, Shun; Liu, Ma-Feng; Zhao, Xin-Xin; Chen, Xiao-Yue

    2017-01-01

    Apoptosis, an important innate immune mechanism that eliminates pathogen-infected cells, is primarily triggered by two signalling pathways: the death receptor pathway and the mitochondria-mediated pathway. However, many viruses have evolved various strategies to suppress apoptosis by encoding anti-apoptotic factors or regulating apoptotic signalling pathways, which promote viral propagation and evasion of the host defence. During its life cycle, α-herpesvirus utilizes an elegant multifarious anti-apoptotic strategy to suppress programmed cell death. This progress article primarily focuses on the current understanding of the apoptosis-inhibition mechanisms of α-herpesvirus anti-apoptotic genes and their expression products and discusses future directions, including how the anti-apoptotic function of herpesvirus could be targeted therapeutically. PMID:28406478

  10. Profiles of Everyday Thought Suppression

    OpenAIRE

    Ie, Amanda Yen Lin

    2014-01-01

    The present research assessed whether levels of depression, anxiety and worry, obsessive-compulsive distress, and psychopathy were differentially related to distinct thought suppression profiles. As a means to achieving this goal, the Profiles of Everyday Thought Suppression (PETS) scale was constructed to measure the frequencies with which various target thoughts are suppressed. The PETS scale demonstrated good internal consistency and test-retest reliability, and scores were positively co...

  11. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  12. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  13. Novel oncolytic viral therapies in patients with thoracic malignancies

    Directory of Open Access Journals (Sweden)

    Ahmad Z

    2016-12-01

    Full Text Available Zeeshan Ahmad, Robert A Kratzke Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA Abstract: Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with precise cellular tropism and the identification of cell-surface receptors that facilitate viral transfer to the tissue of interest. Current research is also focused on targeting metastatic disease by sustaining the release of progeny viruses from infected tumor cells and understanding indirect tumor cell killing through immune-mediated mechanisms of virotherapy. The purpose of this review is to critically evaluate recent evidence on the clinical development of tissue-specific viruses capable of targeting tumor cells and eliciting secondary immune responses in lung cancers and mesothelioma. Keywords: lung cancer, mesothelioma, VSV, adenovirus, measles

  14. Targeting Localized Immune Suppression Within the Tumor Through Repeat Cycles of Immune Cell-oncolytic Virus Combination Therapy

    OpenAIRE

    Thorne, Stephen H; Liang, Wenchun; Sampath, Padma; Schmidt, Tobi; Sikorski, Rachel; Beilhack, Andreas; Contag, Christopher H.

    2010-01-01

    A major limitation to the use of immunotherapy in the treatment of cancer has been the localized immune suppressive environment within the tumor. Although there is evidence that tumor-selective (oncolytic) viruses may help to overcome this immune suppression, a primary limitation to their use has been limited systemic delivery potential, especially in the face of antiviral immunity. We recently demonstrated that tumor-trafficking immune cells can efficiently deliver oncolytic viral therapies ...

  15. Regulatory T cells in acute dengue viral infection.

    Science.gov (United States)

    Jayaratne, Eresha; Wijeratne, Dulharie; Fernando, Samitha; Kamaladasa, Achala; Gomes, Laksiri; Wijewickrama, Ananda; Ogg, Graham Stuart; Malavige, Gathsaurie Neelika

    2017-11-15

    Although regulatory T cells (Tregs) have been shown to be expanded in acute dengue, their role in pathogenesis and their relationship to clinical disease severity, and extent of viraemia have not been fully evaluated. The frequency of Tregs was assessed in 56 adult patients with acute dengue, by determining the proportion of FOXP3 expressing CD4+ CD25+ T cells (FOXP3+ cells). DENV viral loads were measured by quantitative real time PCR and DENV specific T cell responses were measured by ex vivo IFNγ ELISpot assays to overlapping peptide pools of DENV-NS3, NS1 and NS5. CD45RA and CCR4 were used to phenotype different subset of T cells and their suppressive potential was assessed by their expression of CTLA-4 and Fas. While the frequency of FOXP3+ cells, in patients was significantly higher (pT cell responses. The FOXP3+ cells of patients with acute dengue were predominantly CD45RA+ FOXP3low , followed by CD45RA-FOXP3low , with only a small proportion of FOXP3+ cells being of the highly suppressive effector Treg subtype. Expression of CCR4 was also low in the majority of T cells, with only CCR4 only being expressed at high levels in the effector Treg population. Therefore, although FOXP3+ cells are expanded in acute dengue, they predominantly consist of naive Tregs, with poor suppressive capacity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Specific interaction between hnRNP H and HPV16 L1 proteins: Implications for late gene auto-regulation enabling rapid viral capsid protein production

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min; Huang, Hui [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhang, Jun; Xia, Ning-Shao [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China); Miao, Ji, E-mail: jmiao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhao, Qinjian, E-mail: qinjian_zhao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China)

    2013-01-18

    Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.

  17. Viral fitness: definitions, measurement, and current insights

    Science.gov (United States)

    Wargo, Andrew R.; Kurath, Gael

    2012-01-01

    Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

  18. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  19. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  20. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  1. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  2. CHOLESTASIS IN ACUTE AND CHRONIC VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    V. F. Uchaikin

    2014-01-01

    Full Text Available We observed 43 patients with cholestasis (21 — with acute viral hepatitis A and B and 22 — with chronic viral hepatitis B and C. Etiological diagnosis was based on the identification of specific markers of the spectrum. These 43 patients in addition to basic therapy ursodeoxycholic acid as a drug Ursosan of company «PRO.MED.CS Praha a.s.» (CzechRepublic. The control group consisted of 17 patients with acute viral hepatitis. Clinical signs are jaundice and itching of the skin, abdominal pain, significant hepatomegaly. Serum bilirubin level rises due to the conjugated fraction, alkaline phosphatase, gamma-glutamyltranspeptidase. When ultrasound revealed dilated bile ducts in the liver parenchyma, reactive edema of the gallbladder wall, signs gipomotornoy dyskinesia. Appointment ursosan in acute and chronic viral hepatitis occurring with cholestasis leads to the clinical and biochemical effects, and has a beneficial effect on the state of the liver and gall bladder.

  3. Characterization of the viral O-glycopeptidome

    DEFF Research Database (Denmark)

    Cló, Emiliano; Kracun, Stjepan K; Nudelman, Aaron S

    2012-01-01

    also lead to aberrant glycosylation that may elicit immunity. Our knowledge of immunity to aberrant viral glycans and glycoproteins is limited, potentially due to technical limitations in identifying immunogenic glycans and glycopeptide epitopes. This work describes three different complementary...

  4. [Pediatrics. New treatment options for viral bronchiolitis].

    Science.gov (United States)

    Rochat, I; Hafen, G

    2013-01-16

    The combination of nebulized epinephrine and high dose dexamethasone, or nebulized hypertonic saline, are promising new therapeutic strategies for viral bronchiolitis in the young infant. However, further research is needed before a general recommendation can be given.

  5. Drug Use and Viral Infections (HIV, Hepatitis)

    Science.gov (United States)

    ... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... as sharing drug-use equipment and having unprotected sex, which can lead to these infections. Getting treatment. ...

  6. transfusion transmissible viral infections among potential blood

    African Journals Online (AJOL)

    boaz

    Key words: Transfusion Transmissible Infections, HIV, Hepatitis B, Hepatitis C, Blood Donors,. University College Hospital (UCH), ELISA. INTRODUCTION. The most common diseases transmitted in blood transfusions are viral infections. Transfusion- transmissible infectious agents such as human immunodeficiency virus ...

  7. Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia.

    Science.gov (United States)

    Elalfy, Mohsen S; Nugent, Diane

    2016-04-01

    Immune thrombocytopenia (ITP) might be preceded by silent or overt viral infections. Similarly, anti-viral drugs and viral vaccines could also trigger ITP and might play a central role in its pathogenesis. The seasonal nature of childhood ITP suggests that viral infections might initiate immune responses that increase the predisposition and occurrence of ITP. Active cytomegalovirus or Epstein-Barr virus should be considered in differential diagnosis when thrombocytopenia is associated with lymphadenopathy, especially with splenomegaly. This review will focus on the specific association of ITP in association with viral disease and vaccinations, and will discuss the effectiveness of current therapies in light of our current understanding of viral-associated ITP. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Viral Management as a New Type of Enterprise Management in Coal Industry

    Directory of Open Access Journals (Sweden)

    Garafonova Olga

    2017-01-01

    Full Text Available The article considers the evolution of the concept of “management”. The Internet analysis of the concept of “viral management” was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to “infect” the organization and, mainly, employees with one or another “virus” in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal “obsession” with this or other innovation, involvement of an informal personal factor.

  9. Viral Management as a New Type of Enterprise Management in Coal Industry

    Science.gov (United States)

    Garafonova, Olga; Grigashkina, Svetlana; Zhosan, Anna

    2017-11-01

    The article considers the evolution of the concept of "management". The Internet analysis of the concept of "viral management" was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to "infect" the organization and, mainly, employees with one or another "virus" in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal "obsession" with this or other innovation, involvement of an informal personal factor.

  10. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  11. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  12. Screening for suppression in young children : the Polaroid Suppression test

    NARCIS (Netherlands)

    Pott, JWR; Oosterveen, DK; Van Hof-van Duin, J

    1998-01-01

    Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

  13. Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection.

    Science.gov (United States)

    Murira, Armstrong; Lamarre, Alain

    2016-01-01

    Type I interferons (IFN-I) have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs), which upregulate the effector function of immune cells (e.g., dendritic cells, B cells, and T cells) toward successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs, and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make toward establishing the dichotomous nature of IFN-I responses. The aim of this mini review is to (i) summarize the interaction between IFN-I and downstream effector responses and therefore (ii) delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues toward more effective therapeutic and prophylactic measures against chronic viral infections.

  14. [Liver hemosiderosis study in chronic viral hepatitis].

    Science.gov (United States)

    Cojocariu, Camelia; Trifan, Anca; Mihailovici, Maria Sultana; Danciu, M; Stanciu, C

    2008-01-01

    In chronic viral hepatitis the histopathological exam can reveal the presence of liver iron deposits in 10 to 73% of patients. Iron deposits are usually found in Kupffer cells, in endothelial cells and portal macrophages, and extremely rarely in hepatocytes. To evaluate the incidence of hepatic hemosiderosis in chronic viral hepatitis. 549 morphopathological features of liver biopsy specimens performed in the Gastroenterology and Hepatology Institute IaSi, between January 1 2003 and December 31 2007 have been analyzed. Semiquantitative assessment of the degree of hepatic iron overload was performed and the localization of haemosiderin deposits: at the level of hepatocytes, the reticuloendothelial system or mixedly. The same anatomopathologist examined the blades and interpreted the results. The medium age of patients who underwent liver biopsy was 45.08 years +/- 10.045. Positive iron staining was found in 22.8% of cases, more frequently in males (31%), and in 91.82% of cases iron deposits were grade 1-2. The association of alcoholic etiology did not influence the incidence of hemosiderosis: 23% in patients with hepatitis and no ethanol exposure vs 25% in cases of strictly viral etiology. Deposits of haemosiderin were more frequent in viral hepatitis B (38.6%) than in viral hepatitis C (26.9%). In 34% of cases stainable iron was found only in reticuloendothelial system and in 46% of cases both in Kupffer cells and hepatocytes. Almost a quarter of chronic viral hepatitis cases are associated with liver deposits of haemosiderin, with features of secondary iron overload (deposits localized in the mesenchymal areas or mixedly). There is a higher risk of hemosiderosis in men, especially for those between 30 and 50. Liver iron overload levels in chronic viral hepatitis are, in most cases, low or medium, and the association with an alcoholic etiology does not influence the incidence of hemosiderosis in chronic viral hepatitis.

  15. Institute of Medicine's Report on Viral Hepatitis

    Centers for Disease Control (CDC) Podcasts

    2010-05-18

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the 2010 report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C, from the Institute of Medicine.  Created: 5/18/2010 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 5/18/2010.

  16. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    Award Number: W81XWH-11-1-0387 TITLE: Viral Oncolytic Therapeutics for Neoplastic Meningitis PRINCIPAL INVESTIGATOR: Mikhail Papisov, PhD...SUBTITLE Viral Oncolytic Therapeutics for Neoplastic Meningitis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0387 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...for neoplastic meningitis ( meningeal metastasis of breast cancer). The proposed therapy will be based on direct (intrathecal) administration of

  17. Bacterial and Viral Fish Diseases in Turkey

    OpenAIRE

    Öztürk, Rafet Çagrı; Altınok, İlhan

    2014-01-01

    This review summarizes the state of knowledge about the major bacterial and viral pathogens of fish found in Turkey. It also considers diseases prevention and treatment. In this study, peer reviewed scientific articles, theses and dissertations, symposium proceedings, government records as well as recent books, which published between 1976 and 2013 were used as a source to compile dispersed literature. Bacterial and viral disease problems were investigated during this period in Turkey. Total ...

  18. Rapid and highly fieldable viral diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  19. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  20. Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

    Directory of Open Access Journals (Sweden)

    Levi-Drummer Rachel S

    2001-12-01

    Full Text Available Abstract Background High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. Methods A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15 with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9 with no dose reduction. Results Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. Conclusions These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.

  1. Viral Metagenomics: MetaView Software

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, C; Smith, J

    2007-10-22

    The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

  2. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  3. Bioinformatics tools for analysing viral genomic data.

    Science.gov (United States)

    Orton, R J; Gu, Q; Hughes, J; Maabar, M; Modha, S; Vattipally, S B; Wilkie, G S; Davison, A J

    2016-04-01

    The field of viral genomics and bioinformatics is experiencing a strong resurgence due to high-throughput sequencing (HTS) technology, which enables the rapid and cost-effective sequencing and subsequent assembly of large numbers of viral genomes. In addition, the unprecedented power of HTS technologies has enabled the analysis of intra-host viral diversity and quasispecies dynamics in relation to important biological questions on viral transmission, vaccine resistance and host jumping. HTS also enables the rapid identification of both known and potentially new viruses from field and clinical samples, thus adding new tools to the fields of viral discovery and metagenomics. Bioinformatics has been central to the rise of HTS applications because new algorithms and software tools are continually needed to process and analyse the large, complex datasets generated in this rapidly evolving area. In this paper, the authors give a brief overview of the main bioinformatics tools available for viral genomic research, with a particular emphasis on HTS technologies and their main applications. They summarise the major steps in various HTS analyses, starting with quality control of raw reads and encompassing activities ranging from consensus and de novo genome assembly to variant calling and metagenomics, as well as RNA sequencing.

  4. Generating viral metagenomes from the coral holobiont

    Directory of Open Access Journals (Sweden)

    Karen Dawn Weynberg

    2014-05-01

    Full Text Available Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis.

  5. Suppression of HIV-1 viral load after multiple changes in high active ...

    African Journals Online (AJOL)

    International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts. INTRODUCTION.

  6. Genetic evolution of HIV in patients remaining on a stable HAART regimen despite insufficient viral suppression

    DEFF Research Database (Denmark)

    Kristiansen, Thomas B; Pedersen, Anders; Eugen-Olsen, Jesper

    2005-01-01

    consistent HIV-RNA levels above 200 copies/ml were included in the study. The study period spanned at least 12 months and included 47 plasma samples from 17 patients that were sequenced and analysed with respect to evolutionary changes. At inclusion, the median CD4 count was 300 cells/ml (inter......-quartile range (IQR): 231-380) and the median HIV-RNA was 2000 copies/ml (IQR: 1301-6090). Reverse transcription inhibitor (RTI) mutations increased 0.5 mutations per y (STD = 0.8 mutations per y), while major protease inhibitor (PI) resistance mutations increased at a rate of 0.2 mutations per y (STD = 0.......8 mutations per y) and minor PI resistance mutations increased at a rate of 0.3 mutations per y (STD = 0.7 mutations per y). The rate at which RTI mutations accumulated decreased during the study period (p = 0.035). Interestingly, the rate of mutation accumulation was not associated with HIV-RNA level...

  7. Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

    Directory of Open Access Journals (Sweden)

    Shin Hashimoto

    Full Text Available Stress granules (SGs are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV induced SGs depending on activation of protein kinase R (PKR. MuV infection strongly induced interferon (IFN-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3 via retinoic acid inducible gene-I (RIG-I and the mitochondrial antiviral signaling (MAVS pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1 mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

  8. Viral infection and host defense.

    Science.gov (United States)

    Carter, W A; De Clercq, E

    1974-12-27

    Double-stranded RNA, made as an intermediary substance in the replication of most, if not all, viruses, may play a much more important role in the pathogenesis and the recovery from virus infections than has hitherto been suspected. Apparently, dsRNA is used by both the challenge virus and the host cell in an attempt to gain "molecular control." Double-stranded RNA exerts a set of effects, which may be well balanced, not only at the level of the individual cell but also at the complex assemblage of these cells termed the organism (Fig. 1). In the cell, interferon synthesis is triggered, although interferon mRNA translation may not occur if dsRNA shuts off protein synthesis too quickly. In the whole organism, the disease severity will depend on how certain toxic reactions evoked by infection (such as cell necrosis and fever) are counterbalanced by an increase in the host defense mechanisms (for example, immune responsiveness and interferon production). Many aspects of the response, relating to either progress of, or recovery from, the disease, can be explained on the basis of a dsRNA. In addition to drawing attention to the biodynamic role of dsRNA, our hypothesis suggests specific experimental vectors designed to enhance our information on the molecular basis of the morbid process which occurs with viral infection. Finally, we suggest that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given dsRNA molecule always exists. Namely, each deviation from a perfectly double-helical arrangement introduces the possibility for emphasizing one biological reactivity at the expense of another. This latter structure-activity property may partially account for the extreme apparent diversity, commonly encountered, in the presentations of virologic illness. Appendix note added in proof. Subsequent to submission of this text, we have found that the potent mitogen effect of dsRNA for

  9. Crop rotation and its ability to suppress perennial weeds

    OpenAIRE

    Askegaard, Margrethe

    2016-01-01

    The appropriate combination of crops and green manures prevents spread of perennial weeds and increases crop yields and quality. Weed-suppressing crop rotations are absolutely essential for sustainable organic arable farming. Practical recommendation Basic rules • Implement green manures, such as clover or lucerne, in at least 20 % of the rotation. • Do not grow more than 50 % of cereals with low weed competitiveness in the rotation. Do not cultivate such crops for more than 2 con...

  10. An Alternative to Thought Suppression?

    Science.gov (United States)

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  11. Inducing amnesia through systemic suppression

    Science.gov (United States)

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  12. Molecular piracy: the viral link to carcinogenesis.

    Science.gov (United States)

    Flaitz, C M; Hicks, M J

    1998-11-01

    The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous

  13. Lactoferrin for prevention of common viral infections.

    Science.gov (United States)

    Wakabayashi, Hiroyuki; Oda, Hirotsugu; Yamauchi, Koji; Abe, Fumiaki

    2014-11-01

    Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. APLASTIC ANEMIA AND VIRAL HEPATITIS

    Directory of Open Access Journals (Sweden)

    Laura Cudillo

    2009-11-01

    target organ of the immune  response is the liver as suggested by the time interval between hepatitis and the onset of bone marrow failure.

    Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis.

    Recently in HAA it has been demonstrated intrahepatic  and blood lymphocytes with  T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia.

  15. Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10 producing CD4⁺ T cells.

    Directory of Open Access Journals (Sweden)

    Gavin M Mason

    Full Text Available Human cytomegalovirus (HCMV is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo.

  16. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Organizing for Sustainability

    Science.gov (United States)

    Brown, William M.; Hamburger, Michael W.

    2012-01-01

    A successful campus sustainability effort catalyzes broad engagement of the campus community and integration of sustainability principles into the academic and operational components of campus life. Although many universities have embraced sustainability as a new core value, others have been more sluggish in adopting sustainability principles to…

  18. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  19. Viral Hepatitis and Liver Cancer on the Island of Guam

    OpenAIRE

    Haddock, RL; Paulino, YC; Bordallo, R

    2013-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry. The number of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to ...

  20. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  1. View and review on viral oncology research

    Directory of Open Access Journals (Sweden)

    Parolin Cristina

    2010-05-01

    Full Text Available Abstract To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/. According to the World Health Organization (WHO, roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.

  2. Pediatric Viral Exanthema: A Review Article

    Directory of Open Access Journals (Sweden)

    Mohammed Jafar Saffar

    2017-04-01

    Full Text Available Context Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions. Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe and benign types is clinically important and life-saving. Evidence Acquisition In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”. Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded. Results Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be categorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric or the general term, which denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like infection. Conclusions Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues and rash characteristics is of great significance.

  3. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  4. Sustainable Investment. Literature Overview

    Energy Technology Data Exchange (ETDEWEB)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-08-15

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns sustainability at the investment, fund or portfolio level and involves screening the sustainability of companies before investing in them. This report highlights leading literature and empirical findings on 'sustainable investment', amongst others addressing the economic rationale for CSR and SRI. This report is part of a set of SEO-reports on finance and sustainability. The other reports deal with: Financing the Transition to Sustainable Energy; Carbon Trading; Innovations in financing environmental and social sustainability.

  5. Contaminants as viral cofactors: assessing indirect population effects

    Science.gov (United States)

    Springman, Katherine R.; Kurath, Gael; Anderson, James J.; Emlen, John M.

    2005-01-01

    Current toxicological methods often miss contaminant effects, particularly when immune suppression is involved. The failure to recognize and evaluate indirect and sublethal effects severely limits the applicability of those methods at the population level. In this study, the Vitality model is used to evaluate the population level effects of a contaminant exerting only indirect, sublethal effects at the individual level. Juvenile rainbow trout (Oncorhynchus mykiss) were injected with 2.5 or 10.0 mg/kg doses of the model CYP1A inducer, β-naphthoflavone (BNF) as a pre-stressor, then exposed to a challenge dose of 102 or 104 pfu/fish of infectious hematopoietic necrosis virus (IHNV), an important viral pathogen of salmonids in North America. At the end of the 28-d challenge, the mortality data were processed according to the Vitality model which indicated that the correlation between the average rate of vitality loss and the pre-stressor dose was strong:R2 = 0.9944. Average time to death and cumulative mortality were dependent on the BNF dose, while no significant difference between the two viral dosages was shown, implying that the history of the organism at the time of stressor exposure is an important factor in determining the virulence or toxicity of the stressor. The conceptual framework of this model permits a smoother transfer of results to a more complex stratum, namely the population level, which allows the immunosuppressive results generated by doses of a CYP1A inducer that more accurately represent the effects elicited by environmentally-relevant contaminant concentrations to be extrapolated to target populations. The indirect effects of other environmental contaminants with similar biotransformation pathways, such as polycyclic aromatic hydrocarbons (PAH), could be assessed and quantified with this model and the results applied to a more complex biological hierarchy.

  6. T cell inactivation by poxviral B22 family proteins increases viral virulence.

    Directory of Open Access Journals (Sweden)

    Dina Alzhanova

    2014-05-01

    Full Text Available Infections with monkeypox, cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population, but little is known about their mechanisms of virulence and immune evasion. We now demonstrate that B22 proteins, encoded by the largest genes of these viruses, render human T cells unresponsive to stimulation of the T cell receptor by MHC-dependent antigen presentation or by MHC-independent stimulation. In contrast, stimuli that bypass TCR-signaling are not inhibited. In a non-human primate model of monkeypox, virus lacking the B22R homologue (MPXVΔ197 caused only mild disease with lower viremia and cutaneous pox lesions compared to wild type MPXV which caused high viremia, morbidity and mortality. Since MPXVΔ197-infected animals displayed accelerated T cell responses and less T cell dysregulation than MPXV US2003, we conclude that B22 family proteins cause viral virulence by suppressing T cell control of viral dissemination.

  7. Dexamethasone treatment decreases replication of viral hemorrhagic septicemia virus in Epithelioma papulosum cyprini cells.

    Science.gov (United States)

    Kim, Min Sun; Lee, Su Jin; Choi, Seung Hyuk; Kang, Yue Jai; Kim, Ki Hong

    2017-05-01

    The expression of Mx1 in EPC cells after treatment with poly(I:C) or infection with viral hemorrhagic septicemia virus (VHSV) was significantly suppressed by treatment with dexamethasone. However, the titer of VHSV did not increase but instead decreased after dexamethasone treatment. This suggests that dexamethasone not only downregulates type I IFN but also affects certain factors that are necessary for VHSV replication. An important effect of HSP90 on replication of RNA viruses and downregulation of HSP90 by glucocorticoids have been reported. In this study, dexamethasone downregulated HSP90α expression in EPC cells that were stimulated with poly(I:C) or infected with VHSV. Furthermore, cells treated with an HSP90 inhibitor, geldanamycin, showed significantly decreased titers of VHSV, suggesting that HSP90 may be an important host component involved in VHSV replication, and HSP90 inhibition might be one of the causes for the observed reduction in viral titer caused by dexamethasone treatment.

  8. Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Valerie Le Sage

    2016-05-01

    Full Text Available The mammalian target of rapamycin (mTOR is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors and intracellular (energy status molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs.

  9. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  10. Menstrual suppression in the adolescent.

    Science.gov (United States)

    Kantartzis, Kelly L; Sucato, Gina S

    2013-06-01

    Menstrual suppression, the use of contraceptive methods to eliminate or decrease the frequency of menses, is often prescribed for adolescents to treat menstrual disorders or to accommodate patient preference. For young women using hormonal contraceptives, there is no medical indication for menstruation to occur monthly, and various hormonal contraceptives can be used to decrease the frequency of menstruation with different side effect profiles and rates of amenorrhea. This article reviews the different modalities for menstrual suppression, common conditions in adolescents which may improve with menstrual suppression, and strategies for managing common side effects. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  11. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  12. Shedding new light on viral photosynthesis.

    Science.gov (United States)

    Puxty, Richard J; Millard, Andrew D; Evans, David J; Scanlan, David J

    2015-10-01

    Viruses infecting the environmentally important marine cyanobacteria Prochlorococcus and Synechococcus encode 'auxiliary metabolic genes' (AMGs) involved in the light and dark reactions of photosynthesis. Here, we discuss progress on the inventory of such AMGs in the ever-increasing number of viral genome sequences as well as in metagenomic datasets. We contextualise these gene acquisitions with reference to a hypothesised fitness gain to the phage. We also report new evidence with regard to the sequence and predicted structural properties of viral petE genes encoding the soluble electron carrier plastocyanin. Viral copies of PetE exhibit extensive modifications to the N-terminal signal peptide and possess several novel residues in a region responsible for interaction with redox partners. We also highlight potential knowledge gaps in this field and discuss future opportunities to discover novel phage-host interactions involved in the photosynthetic process.

  13. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji

    2015-10-22

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  14. [Promotion of Porphyromonas gingivalis to viral disease].

    Science.gov (United States)

    Tiantian, Meng; Xin, Li

    2016-08-01

    Chronic periodontitis is one of the most common oral diseases in humans, the main recognized pathogenic bac-terium of which is the Porphyromonas gingivalis. Various types of viruses have been detected in periodontal disease in situ, and the joint action of viral and bacterial pathogens infection mechanism are complicated. Porphyromonas gingivalis has the characteristics resulting from the interaction with a variety of bacterium viruses, which may be the reason for chronic perio-dontitis being a protracted disease associated with a variety of systemic diseases. In this paper, we reviewed the relationship between Porphyromonas gingivalis and viral diseases to provide a new idea for the treatment of patients with periodontal disease and viral infections.

  15. Cochrane Corner: Corticosteroids for viral myocarditis.

    Science.gov (United States)

    Caldeira, Daniel; Lopes, Luís R; Vaz-Carneiro, António; Costa, João

    2015-01-01

    The causes of myocarditis are diverse, but a viral etiology is the most common. In this systematic review by the Cochrane Collaboration, the authors assessed the efficacy of corticosteroid therapy in patients with viral myocarditis. Eight randomized controlled trials with 719 patients (two trials in pediatric populations) were included for analysis. Pooled results did not show significant differences in mortality with the use of corticosteroids. Patients on corticosteroid therapy had significantly higher post-treatment left ventricular ejection fraction values compared to control. These results are limited by the significant heterogeneity associated with clinical trials. The best available evidence does not support the routine use of corticosteroids in patients with viral myocarditis. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  16. Hepatitis viral load correlates to glutathione levels.

    Science.gov (United States)

    1998-01-01

    Several recent scientific articles have found a direct correlation between Glutathione levels and viral activity for hepatitis B and C. When viral load increases, Glutathione decreases. Researchers from Germany report that adding NAC (N-acetyl cysteine) to HBV producing cells lines can reduce hepatitis viral load 50 fold. Glutathione is used by the liver to help break down toxins. Patients who have chronic infection for more than 90 days should ask their physicians to check their Glutathione levels. A test kit is available from ImmunoSciences Labs; contact information is included. An amino acid, L-Glutamine, can be used with Alpha Lipoic Acid and NAC to increase Glutathione levels. Chlorophyll also offers benefits to people with hepatitis and other infections. Instructions on how to use a special retention enema containing chlorophyll, water, and apple cider vinegar are provided.

  17. Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome

    Science.gov (United States)

    Lu, Rui; Folimonov, Alexey; Shintaku, Michael; Li, Wan-Xiang; Falk, Bryce W.; Dawson, William O.; Ding, Shou-Wei

    2004-11-01

    Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the 20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although none of the CTV proteins prevented DNA methylation of the transgene, export of the silencing signal (capable of mediating intercellular silencing spread) was detected only from the F1 plants expressing p23 and not from the CP- or p20-expressing F1 plants, demonstrating suppression of intercellular silencing by CP and p20 but not by p23. Thus, intracellular and intercellular silencing are each targeted by a CTV protein, whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses intercellular silencing without interfering with intracellular silencing. The novel property of CP suggests a mechanism distinct to p20 and all of the other viral suppressors known to interfere with intercellular silencing and that this class of viral suppressors may not be consistently identified by Agrobacterium coinfiltration because it also induces RNA silencing against the infiltrated suppressor transgene. Our analyses reveal a sophisticated viral counter-defense strategy that targets the silencing antiviral pathway at multiple steps and may be essential for protecting CTV with such a large RNA genome from antiviral silencing in the perennial tree host. RNA interference | citrus tristeza virus | virus synergy | antiviral immunity

  18. How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections ▿

    Science.gov (United States)

    Ubol, Sukathida; Halstead, Scott B.

    2010-01-01

    Preexisting antibodies may enhance viral infections. In dengue, nonneutralizing antibodies raised by natural infection with one of four dengue viruses (DENVs) may enhance infection with a different virus by a process we term “intrinsic antibody-dependent enhancement” (iADE). In addition, nonprotective antibodies raised by formalin-inactivated respiratory syncytial virus (RSV) and measles virus vaccines have led to enhanced disease during breakthrough infections. Infections under iADE conditions not only facilitate the process of viral entry into monocytes and macrophages but also modify innate and adaptive intracellular antiviral mechanisms, suppressing type 1 interferon (IFN) production and resulting in enhanced DENV replication. The suppression observed in vitro has been documented in patients with severe (dengue hemorrhagic fever [DHF]) but not in patient with mild (dengue fever [DF]) secondary dengue virus infections. Important veterinary viral infections also may exhibit iADE. It is thought that use of formalin deconforms viral epitopes of RSV, resulting in poor Toll-like receptor (TLR) stimulation; suboptimal maturation of dendritic cells with reduced production of activation factors CD40, CD80, and CD86; decreased germinal center formation in lymph nodes; and the production of nonprotective antibodies. These antibodies fail to neutralize RSV, allowing replication with secondary stimulation of RSV-primed Th2 cells producing more low-avidity antibody, resulting in immune complexes deposited into affected tissue. However, when formalin-inactivated RSV was administered with a TLR agonist to mice, they were protected against wild-type virus challenge. Safe and effective vaccines against RSV/measles virus and dengue virus may benefit from a better understanding of how innate immune responses can promote production of protective antibodies. PMID:20876821

  19. The fecal viral flora of wild rodents.

    Directory of Open Access Journals (Sweden)

    Tung G Phan

    2011-09-01

    Full Text Available The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in

  20. Acute Viral Hepatitis in Pediatric Age Groups

    Directory of Open Access Journals (Sweden)

    Sudhamshu KC

    2014-03-01

    Full Text Available Introduction: Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Methods: Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December2010were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0–5, 5–10 and 5–15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Results: Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%, Hepatitis E virus in 24 (8%, Hepatitis B virus in 15 (5%. In 7(2% patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Conclusions: Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery. Keywords: Acute viral hepatitis; hepatitis A; hepatitis E; herbal medications.

  1. Theoretical and experimental analysis of the impacts of removable storage media and antivirus software on viral spread

    Science.gov (United States)

    Gan, Chenquan; Yang, Xiaofan

    2015-05-01

    In this paper, a new computer virus propagation model, which incorporates the effects of removable storage media and antivirus software, is proposed and analyzed. The global stability of the unique equilibrium of the model is independent of system parameters. Numerical simulations not only verify this result, but also illustrate the influences of removable storage media and antivirus software on viral spread. On this basis, some applicable measures for suppressing virus prevalence are suggested.

  2. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

    Science.gov (United States)

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-06-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

  3. Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes

    Science.gov (United States)

    Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

    2012-01-01

    Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65–7.89 × 109 viruses g−1 d−1), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0–8.3 μgC g−1 d−1) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m−2 d−1, thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems. PMID:22170423

  4. Viral pneumonias: Typical and atypical findings

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff-Bleck, M.; Bleck, J.S.; Schirg, E.

    1987-10-01

    The clinical and radiological features of viral pneumonias are summarized and discussed. Although viral infections of the lung belong to atypical pneumonias they demonstrate not always the radiographic pattern of an interstitial pneumonia. Characteristic radiographic findings are quite rare. In most cases the microbial etiology cannot be predicted from chest radiographs. The appearance varies depending on the virulence of the organism and the resistence of the host. In this regard knowledge of epidemiological data as well as patients condition and underlying disease is of utmost importance. Differentiation between community- and hospital-acquired infection may be very helpful.

  5. Viral diseases in honey bee queens

    DEFF Research Database (Denmark)

    Francis, Roy Mathew

    Honey bees are important insects for human welfare, due to pollination as well as honey production. Viral diseases strongly impact honey bee health, especially since the spread of varroa mites. This dissertation deals with the interactions between honey bees, viruses and varroa mites. A new tool...... was developed to diagnose three viruses in honey bees. Quantitative PCR was used to investigate the distribution of two popular viruses in five different tissues of 86 honey bee queens. Seasonal variation of viral infection in honey bee workers and varroa mites were determined by sampling 23 colonies under...

  6. Structure of viral hepatitis in infants

    Directory of Open Access Journals (Sweden)

    T.V. Sorokman

    2017-07-01

    Full Text Available Background. Many current studies are devoted to the study of hepatitis caused by viral infections, which are qualified as TORCH-infection. In infants TORCH-induced lesions prevail in the structure of viral hepatitis, the largest proportion is hepatitis of cytomegalovirus etiology. The purpose was to study the structure of viral hepatitis in infants. Materials and methods. The study included sixty-two children (mean age 1.8 ± 0.9 years born in 2007–2016 treated in Chernivtsi Regional Children’s Clinical Hospital. The comparison group consisted of 36 healthy children of the same age. The pathogens of viral hepatitis B, C, TORCH infections were verified by enzyme immunoassay and polymerase chain reaction. The results of the research were analyzed using computer package Statistica StatSoft Inc. and Excel XP for Windows for a personal computer. Results. The results of the analysis of the liver diseases structure in 62 young children, according to hospital statistics, determined that the overwhelming majority (38 children; 61.3 % had viral hepatitis (VH, the other 24 (38.7 % patients were divided by the etiological structure of liver damage as follows: 8 (12.9 % patients had prolonged conjunctive jaundice, 7 (11.3 % patients had congenital metabolic disorders, 9 (14.5 % patients had congenital hepatobiliary abnomalities. 16.6 % of young children had hepatitis B and C viruses. In 5.8 % of cases VH was caused by viruses of the TORCH group of infections. Conclusions. In the structure of hepatobiliary diseases in infants, viral hepatitis (68.4 % is on the first ranked place. Among the viral hepatitis in children in the first year of life, CMV-hepatitis (68.4 % is most common, in children over 1 year old chronic hepatitis B and C. Severe obstetrical anamnesis, violations of pregnancy, placental infection are rather significant in the group of children with viral hepatitis. The main clinical signs of CMV-hepatitis are prolonged jaundice, cholestasis

  7. Latent Viral Marketing, Concepts and Control Methods

    OpenAIRE

    Sela, Alon; Goldenberg, Dmitri; Ben-Gal, Irad; Shmueli, Erez

    2017-01-01

    Numerus works that study the spread of information in social networks include a spreading mechanism in which a set of nodes is initially infected (i.e. seeded), followed by a viral process, which spontaneously spread the message through the nodes of the network. These models are used to describe the spread of rumors as well as the spread of new products and services. In reality however, it is quite rare that a product or service spreads through a social networks solely by viral forces. It is ...

  8. Cryogenic Acoustic Suppression Testing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will explore and test the feasibility and effectiveness of using a cryogenic fluid (liquid nitrogen) to facilitate acoustic suppression in a...

  9. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...... by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  10. Viruses in the desert: a metagenomic survey of viral communities in four perennial ponds of the Mauritanian Sahara.

    Science.gov (United States)

    Fancello, Laura; Trape, Sébatien; Robert, Catherine; Boyer, Mickaël; Popgeorgiev, Nikolay; Raoult, Didier; Desnues, Christelle

    2013-02-01

    Here, we present the first metagenomic study of viral communities from four perennial ponds (gueltas) located in the central Sahara (Mauritania). Three of the four gueltas (Ilij, Molomhar and Hamdoun) are located at the source of three different wadis belonging to the same hydrologic basin, whereas the fourth (El Berbera) belongs to a different basin. Overall, sequences belonging to tailed bacteriophages were the most abundant in all four metagenomes although electron microscopy and sequencing confirmed the presence of other viral groups, such as large DNA viruses. We observed a decrease in the local viral biodiversity in El Berbera, a guelta with sustained human activities, compared with the pristine Ilij and Molomhar, and sequences related to viruses infecting crop pests were also detected as a probable consequence of the agricultural use of the soil. However, the structure of the El Berbera viral community shared the common global characteristics of the pristine gueltas, that is, it was dominated by Myoviridae and, more particularly, by virulent phages infecting photosynthetic cyanobacteria, such as Prochlorococcus and Synechococcus spp. In contrast, the Hamdoun viral community was characterized by a larger proportion of phages with the potential for a temperate lifestyle and by dominant species related to phages infecting heterotrophic bacteria commonly found in terrestrial environments. We hypothesized that the differences observed in the structural and functional composition of the Hamdoun viral community resulted from the critically low water level experienced by the guelta.

  11. The new normal: immuno-modulatory agents against sepsis immune suppression

    OpenAIRE

    Hutchins, Noelle A.; Unsinger, Jacqueline; Hotchkiss, Richard S.; Ayala, Alfred

    2014-01-01

    Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis...

  12. Suppressed Charmed B Decay

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, Hella Leonie [Vrije Univ., Amsterdam (Netherlands)

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  13. Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent.

    Science.gov (United States)

    Li, Linlin; Deng, Xutao; Mee, Edward T; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D; Delwart, Eric

    2015-03-01

    Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    Science.gov (United States)

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.

  15. Photic effects on sustained performance

    Science.gov (United States)

    French, J.; Whitmore, J.; Hannon, P. J.; Brainard, G.; Schiflett, S.

    1992-01-01

    Research is described which evaluates manipulating environmental light intensity as a means to attenuate fatigue. A counter balanced, within-subjects design was used to compare nine male subjects exposed to dim (100 lux) and bright (3000 lux) light conditions. Oral temperature values were greater for the bright light group over the dim light condition. Melatonin levels were suppressed by bright light treatment. Also, the frequency of eye blink rate was less for subjects during bright over dim light exposure. Light exposure was without effect on subjective fatigue. However, irrespective of light condition, significant effects on confusion, fatigue, and vigor mood dimensions were found as a result of 30 hour sleep deprivation. The findings suggest that bright lights may be used to help sustain nocturnal activity otherwise susceptible to fatigue. Such findings may have implications for the lighting arrangements on space flights during the subjective night for astronauts.

  16. Sustaining Rural Communities through Sustainable Agriculture.

    Science.gov (United States)

    Ikerd, John

    A 5-year collaborative project between Missouri, Michigan State, and Nebraska Universities to provide new opportunities for rural community self-development through sustainable agriculture had mixed results. This happened because community members did not understand the principles of sustainability, and because the extension education system was…

  17. The role of single nucleotide polymorphisms of cytokine genes in viral infections

    Directory of Open Access Journals (Sweden)

    Ćupić Maja

    2014-01-01

    Full Text Available Gene polymorphisms result from evolutionary processes representing mutations that survive in the population with a frequency higher than 1%. The most investigated type of gene polymorphisms are single nucleotide polymorphisms (SNPs. The SNPs of IL-12B (rs 3212227 A/C among a population of kidney graft CMV-seropositive recipients have an impact on a clinical events in cytomegalovirus (CMV disease. Constitutive -308 G/A TNF-α polymorphism (rs1800629 is related to the susceptibility of HR-HPV-associated cervical dysplasia and cancer. SNP located 3 kb upstream of the IL- 28B gene (rs12979860 seems to be the strongest host genetic predictor of sustained virologic response (SVR in hepatitis C genotype 1 patients. It is very important to identify viral and host genetic markers that may facilitate the risk of developing viral disease or some viral-associated cancers. In addition, these markers could be useful in the choice of effective treatments and preventive strategies against virally induced infection. [Projekat Ministarstva nauke Republike Srbije, br. 175073 i br. 175038

  18. Good Friends, Bad News - Affect and Virality in Twitter

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Arvidsson, Adam; Nielsen, Finn Årup

    2011-01-01

    The link between affect, defined as the capacity for sentimental arousal on the part of a message, and virality, defined as the probability that it be sent along, is of significant theoretical and practical importance, e.g. for viral marketing. The basic measure of virality in Twitter is the prob......The link between affect, defined as the capacity for sentimental arousal on the part of a message, and virality, defined as the probability that it be sent along, is of significant theoretical and practical importance, e.g. for viral marketing. The basic measure of virality in Twitter...

  19. Recombinant viruses as vaccines against viral diseases

    Directory of Open Access Journals (Sweden)

    A.P.D. Souza

    2005-04-01

    Full Text Available Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

  20. Why do Individuals Differ in Viral Susceptibility?

    NARCIS (Netherlands)

    Sluijs, van L.; Pijlman, G.P.; Kammenga, J.E.

    2017-01-01

    Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for

  1. Meta-analyses on viral hepatitis

    DEFF Research Database (Denmark)

    Gluud, Lise L; Gluud, Christian

    2009-01-01

    This article summarizes the meta-analyses of interventions for viral hepatitis A, B, and C. Some of the interventions assessed are described in small trials with unclear bias control. Other interventions are supported by large, high-quality trials. Although attempts have been made to adjust...

  2. The Etiology and Pathogenesis of Viral Gastroenteritis.

    Science.gov (United States)

    1983-07-31

    nausea, vomit- ing, low grade fever, abdominal cramps, headache, anorexia, myalgia and malaise. It can be severe, indeed fatal, in the elderly ...infant, debilitated or malnourished patient. Viral gastroenteritis occurs primarily in two epidemiologically distinct clin- ical forms (1). One entity is

  3. Optimal cytoplasmic transport in viral infections.

    Directory of Open Access Journals (Sweden)

    Maria R D'Orsogna

    2009-12-01

    Full Text Available For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such "optimal" infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance.

  4. Viral skin diseases of the rabbit.

    Science.gov (United States)

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Tissue interactions of avian viral attachment proteins

    NARCIS (Netherlands)

    Ambepitiya Wickramasinghe, I.N.

    2015-01-01

    Viruses can infect a wide range of hosts; varying from bacteria and plants to animals and humans. While many viral infections may pass unnoticed, some are of major importance due to their implications on health and welfare of plants, animals and/or humans. In particular, viruses that can infect

  6. Viral Hepatitis and Thrombosis: A Narrative Review

    NARCIS (Netherlands)

    Squizzato, Alessandro; Gerdes, Victor E. A.

    2012-01-01

    Venous thromboembolism (VTE) is a multicausal disease. Among minor risk factors, acute infections in general are associated with a transient increased risk of VTE. However, acute hepatitis is usually not reported as a potential risk factor for VTE. Recent studies suggest a possible role of viral

  7. Sanitation of viral haemorrhagic septicaemia (VHS)

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen

    1998-01-01

    A sanitation programme for stamping-out viral haemorrhagic septicaemia (VHS) was implemented in Denmark in 1965. The programme has resulted in a dramatic reduction in the number of infected rainbow trout farms, from approximate to 400 to 26. The programme is carried out on a voluntary basis...

  8. First Oncolytic Viral Therapy for Melanoma.

    Science.gov (United States)

    Poh, Alissa

    2016-01-01

    The FDA has approved talimogene laherparepvec, or T-VEC, to treat surgically unresectable skin and lymph node lesions in patients with advanced melanoma. T-VEC is the first oncolytic viral therapy to gain regulatory endorsement, based on data from the OPTiM study. ©2016 American Association for Cancer Research.

  9. Fatty acid dynamics during viral infection of

    NARCIS (Netherlands)

    Bale, N.J.; Maat, D.S.; Hopmans, E.C.; Mets, A.; Sinninghe Damsté, J.S.; Brussaard, C.P.D.; Schouten, S.

    2015-01-01

    Previous studies have shown that viral infection can affect the lipid distribution of phytoplankton, specifically the fatty acid (FA) distribution, and has been hypothesized to affect the nutritional value of phytoplankton for higher trophic levels. Here, we report the bulk FA distribution as well

  10. Vaccination of cattle against bovine viral diarrhoea

    NARCIS (Netherlands)

    Oirschot, van J.T.; Bruschke, C.J.M.; Rijn, van P.A.

    1999-01-01

    This brief review describes types and quality (efficacy and safety) of bovine viral diarrhoea virus (BVDV) vaccines that are in the market or under development. Both conventional live and killed vaccines are available. The primary aim of vaccination is to prevent congenital infection, but the few

  11. Sustainable Marketing : The Importance of Being a Sustainable Business

    OpenAIRE

    Reutlinger, Janina

    2012-01-01

    This thesis deals with sustainable marketing, as well as the necessity for more sustainability. The purpose of this thesis was to determine the importance of sustainable marketing for companies. The theoretical part is divided into sustainability and sustainable marketing. Sustainability covers current issues and sustainable development, which form a background for a better understanding of sustainable marketing. Sustainable marketing includes a definition of the concept, as well as susta...

  12. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

    Directory of Open Access Journals (Sweden)

    Pedersen Niels C

    2007-04-01

    Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

  13. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger

    2014-12-01

    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  14. Relationship between antiretrovirals used as part of a cART regimen and CD4 count increases in patients with suppressed viremia

    DEFF Research Database (Denmark)

    Mocroft, A; Phillips, A; Ledergerber, B

    2006-01-01

    BACKGROUND: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml]. OBJECTIVES: To compare the change in CD4 cell count over consecut......BACKGROUND: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) ... from starting cART, age, CD4 at first VL ART. RESULTS: We studied 28418 instances of VL

  15. KSHV Rta promoter specification and viral reactivation

    Directory of Open Access Journals (Sweden)

    Jonathan eGuito

    2012-02-01

    Full Text Available Viruses are obligate intracellular pathogens whose biological success depends upon replication and packaging of viral genomes, and transmission of progeny viruses to new hosts. The biological success of herpesviruses is enhanced by their ability to reproduce their genomes without producing progeny viruses or killing the host cells, a process called latency. Latency permits a herpesvirus to remain undetected in its animal host for decades while maintaining the potential to reactivate, or switch, to a productive life cycle when host conditions are conducive to generating viral progeny. Direct interactions between many host and viral molecules are implicated in controlling herpesviral reactivation, suggesting complex biological networks that control the decision. One viral protein that is necessary and sufficient to switch latent KSHV into the lytic infection cycle is called K-Rta. Rta is a transcriptional activator that specifies promoters by binding direct DNA directly and interacting with cellular proteins. Among these cellular proteins, binding of K-Rta to RBP-Jk is essential for viral reactivation.. In contrast to the canonical model for Notch signaling, RBP-Jk is not uniformly and constitutively bound to the latent KSHV genome, but rather is recruited to DNA by interactions with K-Rta. Stimulation of RBP-Jk DNA binding requires high affinity binding of Rta to repetitive and palindromic CANT DNA repeats in promoters, and formation of ternary complexes with RBP-Jk. However, while K-Rta expression is necessary for initiating KSHV reactivation, K-Rta’s role as the switch is inefficient. Many factors modulate K-Rta’s function, suggesting that KSHV reactivation can be significantly regulated post-Rta expression and challenging the notion that herpesviral reactivation is bistable. This review analyzes rapidly evolving research on KSHV K-Rta to consider the role of K-Rta promoter specification in regulating the progression of KSHV reactivation.

  16. Countermeasures against viral diseases of farmed fish.

    Science.gov (United States)

    Kibenge, Frederick S B; Godoy, Marcos G; Fast, Mark; Workenhe, Samuel; Kibenge, Molly J T

    2012-09-01

    Farmed fish provide an increasing fraction of the human food supply, and are of major economic importance in many countries. As in the case of terrestrial agriculture, bringing together large numbers of animals of a single species (i.e., monoculture) increases the risk of infectious disease outbreaks, including viral infections. Aquaculture, in which farmed fish are kept at high population densities in close proximity with wild fish reservoirs, is ideal for the emergence of wild-type pathogens that exist benignly in local wild fish and/or the spreading of aquatic pathogens to wild fish that enter into or come into close proximity with net cages and with fish escaping from them. This paper provides a general review for the nonspecialist of viral diseases of farmed fish and how they could be prevented or treated. It has five principal objectives: (1) to provide an update on the most important and emerging viral diseases of salmonid aquaculture; (2) to review general aspects of innate antiviral defense against virus infections in fish, including recent advances in antiviral signaling; (3) to discuss current principles and practices of vaccinating fish; (4) to review antiviral drugs that have activity against viruses of farmed fish, and current barriers to employing them in aquaculture; and (5) to discuss the growing use of "functional feeds" in salmonid aquaculture to mitigate viral diseases. In conclusion, despite the challenging aquatic environment, it is expected that well thought-out combinations of vaccination and immunostimulants and/or antiviral drugs could provide solid protection against viral diseases of farmed fish. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    Analysing processes of social learning this work addresses how action research can further new research orientations towards sustainability. Empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating...... on urban sustainability the need to move towards sustainability at societal level is conceptualised as a democratic challenge questioning the way we live on planet earth. By understanding sustainability as an immanent and emergent ability of ecological and social life, continuously to renew itself without...... eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming to provide local citizens...

  18. Handbook of sustainable engineering

    CERN Document Server

    Lee, Kun-Mo

    2013-01-01

    "The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

  19. FORUM: Is Ecotourism Sustainable?

    Science.gov (United States)

    Wall

    1997-07-01

    / It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

  20. Livestock biodiversity and sustainability

    NARCIS (Netherlands)

    Hoffmann, I.

    2011-01-01

    Sustainable development equally includes environmental protection including biodiversity, economic growth and social equity, both within and between generations. The paper first reviews different aspects related to the sustainable use of livestock biodiversity and property regimes that influence

  1. Sustainable Public Bids

    Directory of Open Access Journals (Sweden)

    Gil César Costa de Paula

    2016-06-01

    Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

  2. Contagious Content: Viral Video Ads Identification of Content Characteristics that Help Online Video Advertisements Go Viral

    Directory of Open Access Journals (Sweden)

    Yentl Knossenburg

    2016-12-01

    Full Text Available Why do some online video advertisements go viral while others remain unnoticed? What kind of video content keeps the viewer interested and motivated to share? Many companies have realized the need to innovate their marketing strategies and have embraced the newest ways of using technology, as the Internet, to their advantage as in the example of virality. Yet few marketers actually understand how, and academic literature on this topic is still in development. This study investigated which content characteristics distinguish successful from non-successful online viral video advertisements by analyzing 641 cases using Structural Equation Modeling. Results show that Engagement and Surprise are two main content characteristics that significantly increase the chance of online video advertisements to go viral.  

  3. Indicators for environmental sustainability

    DEFF Research Database (Denmark)

    Dong, Yan; Hauschild, Michael Zwicky

    2017-01-01

    . In this study, we reviewed indicators applied in life cycle assessment (LCA), planetary boundary framework (PB), and Sustainable Development Goals (SDGs) developed under United Nation. The aim is to 1) identify their applications and relevant decision context; 2) Review their indicators and categorize them......Decision making on sustainable consumption and production requires scientifically based information on sustainability. Different environmental sustainability targets exist for specific decision problems. To observe how well these targets are met, relevant environmental indicators are needed...

  4. Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

  5. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  6. Sustainable Learning Organizations

    Science.gov (United States)

    Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

    2011-01-01

    Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

  7. Measuring Educational Sustainability

    Science.gov (United States)

    Selvanathan, Rani G.

    2013-01-01

    There are many definitions that are attributable to the meaning of sustainability. Sustainability can be viewed as long-lasting, effective result of a project, venture, action, or investment without consuming additional future resources. Because of the wide nature of its applicability, a universal measure of sustainability is hard to come by. This…

  8. ORNL Annual Sustainability Report

    Energy Technology Data Exchange (ETDEWEB)

    Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-02-01

    As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

  9. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2017-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  10. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2017-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report ’ i...

  11. Lean maturity, lean sustainability

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke; Nielsen, Jacob

    2007-01-01

    Although lean is rapidly growing in popularity, its implementation is far from problem free and companies may experience difficulties sustaining long term success. In this paper, it is suggested that sustainable lean requires attention to both performance improvement and capability development...... that support lean capability development and consequently, lean sustainability....

  12. Food sustainability: diverging interpretations

    NARCIS (Netherlands)

    Aiking, H.; de Boer, J.

    2004-01-01

    The concept of sustainability in general and food sustainability, in particular, entails many aspects and many interpretations. During a conference on food sustainability a broad, multidisciplinary picture was painted and many key issues were dealt with, from ecology, economy and society. In

  13. Transferring Education for Sustainability

    Science.gov (United States)

    Gafoor, Kunnathodi Abdul; Umer Farooque, T. K.

    2013-01-01

    Sustainability stands for sustaining the past, meeting needs of the present without compromising the ability to meet future needs. It should meet the individual and social needs, present and future needs local and global needs. A sustainable education that meets this requirements surely be a transferable education; an education that transfers from…

  14. Sustainability: An Overview.

    Science.gov (United States)

    Wormsley, W. E.

    1990-01-01

    This article introduces a group of six papers on sustainability of programs for visually handicapped persons in developing countries. Sustainability is discussed from an anthropological perspective, noting the importance of a social soundness analysis and a social impact assessment, enemies of sustainability, and the need for broad local input in…

  15. Sustainability in logistics practice

    NARCIS (Netherlands)

    Hans-Heinrich Glöckner; Reinder Pieters; Stef Weijers

    2009-01-01

    This conceptual paper wants to emphasis the use of the concept of sustainability within logistics and especially transportation. While working on a new tool to help companies develop sustainable European networks, we discovered that we want to use a specific concept of sustainability: People, planet

  16. Asthma exacerbations: Understanding role of viral respiratory tract infections and possible treatment strategies

    Directory of Open Access Journals (Sweden)

    Kavita Sekhri

    2015-01-01

    Full Text Available Asthma is common, affecting around 500 billion people worldwide. It is a complex disease influenced by both genetic and environmental factors. Upper respiratory tract infections with viruses commonly precipitate severe and sustained asthma exacerbations (AEs. Exacerbations are responsible for the enormous amount of emotional and economic stress apart from imposing risk of hospitalization and even death. Hence, agents targeting these infections can contribute toward decreasing asthma morbidity and associated financial burden. Over the past years novel, pharmacological therapies are evolved for the treatment of asthma, but their exact role in exacerbations is still unclear. This article reviews the role of respiratory viral infections in AEs and discusses role of new therapeutic approaches to overcome it. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms such as "asthma," "AE" and "viral respiratory infections." Journal articles published from 2000 to 2013 describing AEs were screened.

  17. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    Science.gov (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  18. Purging device for suppression chamber

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Koichi.

    1987-11-14

    Purpose: To completely drive out air or the like in the suppression chamber in a short period of time thereby protect bent pipes from embrittled rupture. Constitution: Nitrogen gases, etc. entering through the inlet penetration to the inside of a reactor container are guided downwardly through communication pipeways, and the released downwardly in a stable manner while the blowing speed being retained by blowing mechanisms. Released nitrogen gases, etc. diffuse along the water surface of the suppression chamber and fill the inside of the chamber from below. Air, etc. in the suppression chamber prior to the supply of nitrogen gas, etc. is discharged through the exit penetration from the purging discharge pipe smoothly to the outside. In this way, air is replaced with nitrogen gas, etc., the released nitrogen is not directly blown to bent pipe, the operation is simplified, and the charge/discharge operation can be made in a short time efficiently. (Kamimura, M.).

  19. Visual surround suppression in schizophrenia.

    Science.gov (United States)

    Tibber, Marc S; Anderson, Elaine J; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S; Dakin, Steven C

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast - a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target's appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.

  20. p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome.

    Science.gov (United States)

    Darbinian-Sarkissian, N; Darbinyan, A; Otte, J; Radhakrishnan, S; Sawaya, B E; Arzumanyan, A; Chipitsyna, G; Popov, Y; Rappaport, J; Amini, S; Khalili, K

    2006-02-01

    Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27(SJ), present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27(SJ) associates with C/EBPbeta, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27(SJ) with C/EBPbeta and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27(SJ) forces its entry into the nucleus and diminishes the capacity of p27(SJ) to suppress Tat activity, but does not alter its ability to suppress C/EBPbeta activation of the LTR. Results from binding assays showed the inhibitory effect of p27(SJ) on C/EBPbeta interaction with DNA. Finally, our results demonstrate that expression of p27(SJ) decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27(SJ) protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.