Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
1.
PLoS Pathog ; 11(9): e1005153, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26402858

RESUMEN

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.


Asunto(s)
Tejido Adiposo/virología , Reservorios de Enfermedades , Infecciones por VIH/virología , VIH/fisiología , Paniculitis/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/fisiología , Tejido Adiposo/inmunología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Adulto , Anciano , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/virología , Células Cultivadas , Técnicas de Cocultivo , Femenino , VIH/inmunología , VIH/aislamiento & purificación , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata , Macaca fascicularis , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Macrófagos/virología , Masculino , Persona de Mediana Edad , Paniculitis/inmunología , Paniculitis/metabolismo , Paniculitis/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Células del Estroma/inmunología , Células del Estroma/metabolismo , Células del Estroma/patología , Células del Estroma/virología
2.
J Antimicrob Chemother ; 71(11): 3202-3205, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27432601

RESUMEN

OBJECTIVES: Intermittent seminal HIV-RNA detection can occur in MSM despite concomitant plasma virological control on combined ART (cART). We undertook the present study to determine if seminal HIV detection was associated with seminal cytomegalovirus (CMV) detection or detection of HIV-infected cells in semen. METHODS: Longitudinal semen samples from HIV-1-infected MSM on successful cART enrolled in the EVARIST ANRS EP 49 study were analysed. We first conducted a case-control analysis (ratio 1 : 3) to assess HIV-DNA detection in semen cells in the 20 patients with detectable HIV-RNA in seminal plasma (cases) matched with 60 participants with undetectable HIV-RNA (controls) based on total HIV-DNA load in blood cells. Second, we measured CMV-DNA in all seminal plasma samples. RESULTS: HIV-1-DNA in semen cells was detected on at least one sample visit in 12/20 cases and 11/60 controls. Detection of HIV-RNA in seminal plasma was associated significantly with the detection of HIV-DNA in semen cells [OR, 7.6 (95% CI, 2.1-28.4); P = 0.002] when adjusted on total HIV-DNA in blood cells. CMV-DNA was detected in 107/273 seminal plasma samples with a median value of 3.62 log10 copies/mL (IQR, 2.83-4.38), yielding a prevalence of 39.2%. Seminal CMV-DNA shedding [OR, 1.5 (95% CI, 0.6-3.6); P = 0.343] was not associated with the risk of detection of HIV-RNA in seminal plasma. CONCLUSIONS: The presence of HIV-DNA in semen cells was predictive of HIV-RNA detection, suggesting that viral particles arise through local HIV replication by infected semen cells. Despite virological control, compartmentalization of HIV in the genital tract might act in residual replication and transmission.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por Citomegalovirus/virología , ADN Viral/análisis , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , ARN Viral/análisis , Semen/virología , Estudios de Casos y Controles , Citomegalovirus/aislamiento & purificación , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Humanos , Estudios Longitudinales , Masculino , Esparcimiento de Virus
3.
PLoS One ; 12(7): e0180191, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28708873

RESUMEN

BACKGROUND: HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. METHODS: Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment. RESULTS: At enrollment, HIV-RNA load was higher in blood than in semen (median 5.66 vs 4.22 log10 cp/mL, p<0.0001). Semen HIV-RNA load correlated strongly with blood HIV-RNA load (r = 0.81, p = 0.02, the CD4 cell count (r = -0.98, p<0.0001), and the CD4/CD8 ratio (r = -0.85, p<0.01) in acute infection but not in later stages of PHI. Median blood and seminal cellular HIV-DNA levels were 3.59 and 0.31 log10cp/106 cells, respectively. HIV-DNA load peaked in semen later than in blood and then correlated with blood IP10 level (r = 0.62, p = 0.04). HIV-RNA was undetectable in blood and semen after two years of effective cART. Semen HIV-DNA load declined similarly, except in one patient who had persistently high IP-10 and IL-6 levels and used recreational drugs. CONCLUSIONS: HIV reservoir cells are found in semen during PHI, with gradual compartmentalization. Its size was linked to the plasma IP-10 level. Early treatment purges both the virus and infected cells, reducing the high risk of transmission during PHI. CLINICAL TRIALS REGISTRATION: NCT01033760.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , ARN Viral/sangre , Semen/virología , Enfermedad Aguda , Adulto , Relación CD4-CD8 , Ensayo de Inmunoadsorción Enzimática , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Interleucina-6/análisis , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , ARN Viral/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo , Carga Viral , Adulto Joven
4.
PLoS One ; 8(6): e66830, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23826152

RESUMEN

Limited information is available regarding the cellular mechanisms of oxaliplatin-induced painful neuropathy during exposure of patients to this drug. We therefore determined oxidative stress in cultured cells and evaluated its occurrence in C57BL/6 mice. Using both cultured neuroblastoma (SH-SY5Y) and macrophage (RAW 264.7) cell lines and also brain tissues of oxaliplatin-treated mice, we investigated whether oxaliplatin (OXA) induces oxidative stress and apoptosis. Cultured cells were treated with 2-200 µM OXA for 24 h. The effects of pharmacological inhibitors of oxidative stress or inflammation (N-acetyl cysteine, ibuprofen, acetaminophen) were also tested. Inhibitors were added 30 min before OXA treatment and then in combination with OXA for 24 h. In SH-SY5Y cells, OXA caused a significant dose-dependent decrease in viability, a large increase in ROS and NO production, lipid peroxidation and mitochondrial impairment as assessed by a drop in mitochondrial membrane potential, which are deleterious for the cell. An increase in levels of negatively charged phospholipids such as cardiolipin but also phosphatidylserine and phosphatidylinositol, was also observed. Additionally, OXA caused concentration-dependent P2X7 receptor activation, increased chromatin condensation and caspase-3 activation associated with TNF-α and IL-6 release. The majority of these toxic effects were equally observed in Raw 264.7 which also presented high levels of PGE2. Pretreatment of SH-SY5Y cells with pharmacological inhibitors significantly reduced or blocked all the neurotoxic OXA effects. In OXA-treated mice (28 mg/kg cumulated dose) significant cold hyperalgesia and oxidative stress in the tested brain areas were shown. Our study suggests that targeting P2X7 receptor activation and mitochondrial impairment might be a potential therapeutic strategy against OXA-induced neuropathic pain.


Asunto(s)
Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Compuestos Organoplatinos/toxicidad , Receptores Purinérgicos P2X7/metabolismo , Animales , Apoptosis/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Oxaliplatino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA