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Peter Schieberle - One of the best experts on this subject based on the ideXlab platform.

  • Determination of ochratoxin A in food: comparison of a stable isotope dilution assay, liquid chromatography-fluorescence detection and an enzyme-linked immunosorbent assay
    Mycotoxin Research, 2011
    Co-Authors: Michael Lindenmeier, Peter Schieberle
    Abstract:

    Quantitative results for the mycotoxin ochratoxin A (OTA), obtained by a stable isotope dilution assay (Sida) were compared with two commonly used analytical methods for OTA quantitation. For this, different types of food, such as wheat, coffee, sultanas, and blood sausages, were analyzed. Because results obtained by the Sida method were closest to the certified contents of an OTA reference material, data obtained by this method were considered as reference data. For liquid chromatography-fluorescence detection, a clean-up by solid phase extraction on silica was found to be necessary, and a correction for recovery had to be performed to match the data from the Sida experiments. The enzyme-linked immunosorbent assay (ELISA) strongly overestimated the OTA content in coffee and nutmeg therefore an extract clean-up by immunoaffinity chromatography had to be used to match the Sida results. Following this sample preparation, ELISA gave correct qualitative and semiquantitative results, and proved to be a suitable screening method. Sida was also established as a valuable tool to quantify OTA in meat products, when using a clean-up procedure developed recently for blood samples.

  • quantitation of r and s linalool in beer using solid phase microextraction spme in combination with a stable isotope dilution assay Sida
    Journal of Agricultural and Food Chemistry, 2003
    Co-Authors: Martin Steinhaus, Helge T Fritsch, Peter Schieberle
    Abstract:

    A stable isotope dilution assay (Sida) was developed for the quantitation of both linalool enantiomers using synthesized [2H2]R/S-linalool as the internal standard. For enrichment of the target compound from beer, a solid phase microextraction method (SPME) was developed. In comparison to the more time-consuming extraction/distillation cleanup of the beer samples, the results obtained by SPME/Sida were very similar, even under nonequilibration conditions. Analysis of five different types of beer showed significant differences in the linalool concentrations, which were clearly correlated with the intensity of the hoppy aroma note as evaluated by a sensory panel. In addition, significant differences in the R/S ratios were measured in the beers. The SPME/Sida yielded exact data independently from headspace sampling parameters, such as exposure time or ionic strength of the solution. Keywords: Solid phase microextraction; SPME; stable isotope dilution analysis; Sida; linalool; enantiomeric distribution; beer;...

Alfred S Traore - One of the best experts on this subject based on the ideXlab platform.

  • antimalarial activity of Sida acuta burm f malvaceae and pterocarpus erinaceus poir fabaceae
    Journal of Ethnopharmacology, 2003
    Co-Authors: D S Karou, Souleymane Sanon, Mamoudou H Dicko, Jacques Simpore, Alfred S Traore
    Abstract:

    Abstract Among strategies to combat malaria, the search for new antimalarial drugs appears to be a priority. Sheering for new antimalarial activities, four plants of the traditional medicine of Burkina Faso: Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were tested in vitro on fresh clinical isolates of Plasmodium falciparum. The screening showed that Sida acuta has a significant activity (IC50

  • antimalarial activity of Sida acuta burm f malvaceae and pterocarpus erinaceus poir fabaceae
    Journal of Ethnopharmacology, 2003
    Co-Authors: D S Karou, Souleymane Sanon, Mamoudou H Dicko, Jacques Simpore, Alfred S Traore
    Abstract:

    Among strategies to combat malaria, the search for new antimalarial drugs appears to be a priority. Sheering for new antimalarial activities, four plants of the traditional medicine of Burkina Faso: Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were tested in vitro on fresh clinical isolates of Plasmodium falciparum. The screening showed that Sida acuta has a significant activity (IC50 < 5 microg/ml), and Pterocarpus erinaceus has a moderate activity (5 microg/ml < IC50 < 50 microg/ml). Further chemical screening showed that the activity of the most active plant, Sida acuta, was related to its alkaloid contents.

D S Karou - One of the best experts on this subject based on the ideXlab platform.

  • antimalarial activity of Sida acuta burm f malvaceae and pterocarpus erinaceus poir fabaceae
    Journal of Ethnopharmacology, 2003
    Co-Authors: D S Karou, Souleymane Sanon, Mamoudou H Dicko, Jacques Simpore, Alfred S Traore
    Abstract:

    Abstract Among strategies to combat malaria, the search for new antimalarial drugs appears to be a priority. Sheering for new antimalarial activities, four plants of the traditional medicine of Burkina Faso: Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were tested in vitro on fresh clinical isolates of Plasmodium falciparum. The screening showed that Sida acuta has a significant activity (IC50

  • antimalarial activity of Sida acuta burm f malvaceae and pterocarpus erinaceus poir fabaceae
    Journal of Ethnopharmacology, 2003
    Co-Authors: D S Karou, Souleymane Sanon, Mamoudou H Dicko, Jacques Simpore, Alfred S Traore
    Abstract:

    Among strategies to combat malaria, the search for new antimalarial drugs appears to be a priority. Sheering for new antimalarial activities, four plants of the traditional medicine of Burkina Faso: Combretum micranthum, Khaya senegalensis, Pterocarpus erinaceus and Sida acuta, were tested in vitro on fresh clinical isolates of Plasmodium falciparum. The screening showed that Sida acuta has a significant activity (IC50 < 5 microg/ml), and Pterocarpus erinaceus has a moderate activity (5 microg/ml < IC50 < 50 microg/ml). Further chemical screening showed that the activity of the most active plant, Sida acuta, was related to its alkaloid contents.

Rémi Schneider - One of the best experts on this subject based on the ideXlab platform.

  • analysis of ochratoxin a in grapes musts and wines by lc ms ms first comparison of stable isotope dilution assay and diastereomeric dilution assay methods
    Analytica Chimica Acta, 2014
    Co-Authors: Aurélie Roland, Pauline Bros, Anaïs Bouisseau, Florine Cavelier, Rémi Schneider
    Abstract:

    Abstract Ochratoxin A (OTA) exhibits potent nephrotoxic, carcinogenic and teratogenic effects and its maximum level in wines has been set to 2 μg L−1 by regulation. Consequently, the analytical procedures for OTA determination in wines have to be both very sensitive and reliable. In this paper, we compared two quantification methods: the stable isotope dilution assay (Sida) and the diastereomeric dilution assay (DIDA). For this purpose, non-natural analogues of OTA were synthesized: the labeled OTA (OTA-d4) as a diastereomeric mixture for the Sida and one non-natural OTA’s diastereomer (OTA-dia) for the DIDA. To quantify OTA in red grapes, musts or wines, the sample preparation was optimized using immunoaffinity column extraction and the analysis was performed by LC–MS/MS in Multiple Reaction Monitoring mode. A validation procedure in agreement with the International Organization of Vine and Wine recommendations was conducted. It appeared that Sida quantification exhibited excellent sensitivity (LOD

Salomon, Horacio Eduardo - One of the best experts on this subject based on the ideXlab platform.

  • Creación de la colección COVID-19 del Biobanco de Enfermedades Infecciosas en Argentina
    Fundacion Huesped, 2021
    Co-Authors: Longuira Yesica, Ghiglione, Yanina Alexandra, Turk, Gabriela Julia Ana, Salomon, Horacio Eduardo, Polo, Maria Laura, Salvatori Melina, Azzolina Sabrina, Quiroga, María Florencia, Laufer, Natalia Lorna
    Abstract:

    La pandemia de COVID-19 ha puesto en jaque a los sistemas de salud en el mundo; la vinculación entre la investigación biomédica y la práctica asistencial ha probado ser un requisito fundamental para dar respuesta a la misma de manera eficiente y rápida. En este sentido, los biobancos se constituyen como un componente clave ya que favorecen el almacenamiento de grandesvolúmenes de muestras biológicas gestionadas en base a criterios que garanticen su óptima calidad, armonización y seguridad, respetando requisitos éticos y legales que aseguran los derechos de los ciudadanos. La cesión de estas muestras a distintos grupos de investigación promueve el desarrollo de nuevas herramientas diagnósticas y terapéuticas y vacunas.Frente a la llegada del SARS-CoV-2 a la Argentina, el Biobanco de Enfermedades Infecciosas estableció rápidamente la colección COVID-19 constituida por muestras de plasma, suero y células mononucleares de sangre periférica de personas cursando la enfermedad o recuperadas. En solo seis meses se enrolaron 825 donantes, lo que significa alrededor de 14.000 viales dematerial biológico almacenados y a disposición de los investigadores que lo soliciten. A tal efecto, se realizaron seis actos de cesión a diversos grupos pertenecientes a instituciones de investigación, mientras que tres se encuentran en evaluación. Las muestras cedidas hanpermitido, por ejemplo, el desarrollo de kits serológicos de producción nacional; lo que pone de manifiesto que el rápido establecimiento de esta colección, bajo un sistema de gestión eficiente, constituye una herramienta muy valiosa en la respuesta a esta nueva enfermedad.Fil: Longuira, Yesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Polo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salvatori, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Azzolina, Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

  • Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy
    'Oxford University Press (OUP)', 2020
    Co-Authors: Ghiglione, Yanina Alexandra, Trifone, César Ariel, Polo, Maria Laura, Quiroga, María Florencia, Urioste Alejandra, Rhodes Ajantha, Czernikier Alejandro, Sisto Alicia, Patterson Patricia, Salomon, Horacio Eduardo
    Abstract:

    Background Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). Methods In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. Results Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. Conclusions Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.Fil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Polo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Urioste, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Rhodes, Ajantha. University of Melbourne; Australia. Royal Melbourne Hospital; AustraliaFil: Czernikier, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Trifone, César Ariel. University of Melbourne; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sisto, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Patterson, Patricia. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Rolon, Maria Jose. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Bakkour, Sonia. Vitalant Research Institute; Estados UnidosFil: Lewin, Sharon R.. Monash University; Australia. University of Melbourne; AustraliaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentin

  • Hepatitis C Virus (HCV) clearance after treatment with direct-acting antivirals in human immunodeficiency virus (HIV)-HCV coinfection modulates systemic immune activation and HIV transcription on antiretroviral therapy
    'Oxford University Press (OUP)', 2020
    Co-Authors: Ghiglione, Yanina Alexandra, Trifone, César Ariel, Polo, Maria Laura, Quiroga, María Florencia, Urioste Alejandra, Rhodes Ajantha, Czernikier Alejandro, Sisto Alicia, Patterson Patricia, Salomon, Horacio Eduardo
    Abstract:

    Background. Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). Methods. In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/ daclatasvir } ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. Results. Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL- 8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. Conclusions. Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.Fil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Polo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Urioste, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Rhodes, Ajantha. Peter Doherty Institute For Infection And Immunity; AustraliaFil: Czernikier, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Trifone, César Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sisto, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Patterson, Patricia. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Rolón, María José. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Bakkour, Sonia. No especifíca;Fil: Lewin, Sharon R.. Monash University; Australia. Peter Doherty Institute For Infection And Immunity; AustraliaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

  • Interaction between macrophage migration inhibitory factor and CD74 in human immunodeficiency virus type I infected primary monocyte-derived macrophages triggers the production of proinflammatory mediators and enhances infection of unactivated CD4+ T cells
    'Frontiers Media SA', 2018
    Co-Authors: Trifone, César Ariel, Ghiglione, Yanina Alexandra, Salomon, Horacio Eduardo, Salido, Jimena Patricia, Ruiz, María Julia, Quiroga, María Florencia, Leng Lin, Bucala Richard, Turk, Gabriela Julia Ana
    Abstract:

    Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74 membrane expression is upregulated in HIV-1-infected cells and the magnitude of its modulation correlates with immune hyperactivation in HIV-infected individuals. In addition, plasma level of the CD74 activating ligand macrophage migration inhibitory factor (MIF) is increased in infected subjects. However, the role played by MIF/CD74 interaction in HIV pathogenesis remains unexplored. Here, we studied the effect of MIF/CD74 interaction on primary HIV-infected monocyte-derived macrophages (MDMs) and its implications for HIV immunopathogenesis. Confocal immunofluorescence analysis of CD74 and CD44 (the MIF signal transduction co-receptor) expression indicated that both molecules colocalized at the plasma membrane specifically in wild-type HIV-infected MDMs. Treatment of infected MDMs with MIF resulted in an MIF-dependent increase in TLR4 expression. Similarly, there was a dose-dependent increase in the production of IL-6, IL-8, TNFα, IL-1β, and sICAM compared to the no-MIF condition, specifically from infected MDMs. Importantly, the effect observed on IL-6, IL-8, TNFα, and IL-1β was abrogated by impeding MIF interaction with CD74. Moreover, the use of a neutralizing αMIF antibody or an MIF antagonist reverted these effects, supporting the specificity of the results. Treatment of unactivated CD4+ T-cells with MIF-treated HIV-infected MDM-derived culture supernatants led to enhanced permissiveness to HIV-1 infection. This effect was lost when CD4+ T-cells were treated with supernatants derived from infected MDMs in which CD74/MIF interaction had been blocked. Moreover, the enhanced permissiveness of unactivated CD4+ T-cells was recapitulated by exogenous addition of IL-6, IL-8, IL-1β, and TNFα, or abrogated by neutralizing its biological activity using specific antibodies. Results obtained with BAL and NL4-3 HIV laboratory strains were reproduced using transmitted/founder primary isolates. This evidence indicated that MIF/CD74 interaction resulted in a higher production of proinflammatory cytokines from HIV-infected MDMs. This caused the generation of an inflammatory microenvironment which predisposed unactivated CD4+ T-cells to HIV-1 infection, which might contribute to viral spreading and reservoir seeding. Overall, these results support a novel role of the MIF/CD74 axis in HIV pathogenesis that deserves further investigation.Fil: Trifone, César Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salido, Jimena Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ruiz, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Leng, Lin. University of Yale; Estados UnidosFil: Quiroga, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Bucala, Richard. University of Yale; Estados UnidosFil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. UniverSidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

  • Viral replication is enhanced by an HIV-1 intersubtype recombination-derived Vpu protein
    BioMed Central, 2017
    Co-Authors: De Candia, Cristian Ariel, Espada, Constanza Eleonora, Duette Gabriel, Ghiglione, Yanina Alexandra, Turk, Gabriela Julia Ana, Salomon, Horacio Eduardo, Carobene Mauricio
    Abstract:

    Background: Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating recombinant form, CRF12_BF, and many related BF recombinant forms. In these genomic structures a recombination breakpoint frequently involved the vpu coding region. Due to the scarce knowledge of Vpu participation in the virion release process and its impact on pathogenesis and of the functional capacities of intersubtype recombinant Vpu proteins, the aim of this work was to perform a comparative analysis on virion release capacity and relative replication capacity among viral variants harboring either a BF recombinant Vpu or a subtype B Vpu. Results: Our results showed that BF recombinant Vpu was associated to an increased viral particles production when compared to WT B variant in tetherin-expressing cell lines. This observation was tested in the context of a competition assay between the above mentioned variants. The results showed that the replication of the BF Vpu-harboring variant was more efficient in cell cultures than subtype B, reaching a higher frequency in the viral population in a short period of time. Conclusion: This study showed that as a result of intersubtype recombination, a structurally re-organized HIV-1 Vpu has an improved in vitro capacity of enhancing viral replication, and provides evidence of the changes occurring in this protein function that could play an important role in the successful spread of intersubtype recombinant variants.Fil: de Candia, Cristian Ariel. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia Para El Sida; ArgentinaFil: Espada, Constanza Eleonora. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia Para El Sida; ArgentinaFil: Duette, Gabriel. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiglione, Yanina Alexandra. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Turk, Gabriela Julia Ana. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salomon, Horacio Eduardo. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carobene, Mauricio. UniverSidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

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