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1.
AIDS Res Hum Retroviruses ; 36(2): 101-115, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31659912

RESUMEN

Human immunodeficiency virus-1 (HIV-1) causes CD4 T cell depletion through a number of mechanisms, including programmed cell death pathways (both apoptotic and nonapoptotic). In the setting of HIV-1 infection, the enhanced lymphocyte cell death occurs as a consequence of complex interactions between the host immune system and viral factors, which are reviewed herein. On the other hand, the main challenge to HIV-1 eradication is the development of latent infection in a subset of long lived cells, including CD4+ T cells and macrophages, which resist HIV-induced cell death. Understanding the potential mechanisms of how HIV-1 induces lymphocyte cell death is critical to the "kick and kill" cure strategy, which relies on the effective killing of reactivated, HIV-1-infected cells.


Asunto(s)
Muerte Celular/inmunología , Infecciones por VIH/inmunología , Interacciones Microbiota-Huesped/inmunología , Linfocitos/patología , Linfocitos/virología , Apoptosis/inmunología , Autofagia/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , VIH-1 , Humanos , Linfocitos/inmunología , Macrófagos/inmunología , Macrófagos/virología , Necroptosis/inmunología
2.
AIDS ; 33(11): 1757-1763, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31149947

RESUMEN

OBJECTIVE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) dependent apoptosis has been implicated in CD4 T-cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression. DESIGN: Cohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations. METHODS: TRAILshort and TRAIL gene expression in peripheral blood mononuclear cells (PBMCs) was determined by RNA-seq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively. RESULTS: HIV-1 elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P < 0.001) than viremic progressors. CONCLUSION: Reduced TRAILshort expression in PBMCs and plasma is associated with HIV-1 elite controller status.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/sangre , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Viremia/genética , Adulto , Anciano , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , Femenino , Infecciones por VIH/inmunología , VIH-1/crecimiento & desarrollo , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Replicación Viral , Adulto Joven
3.
J Immunol ; 203(3): 718-724, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31189571

RESUMEN

CD4 T cells from HIV-1 infected patients die at excessive rates compared to those from uninfected patients, causing immunodeficiency. We previously identified a dominant negative ligand that antagonizes the TRAIL-dependent pathway of cell death, which we called TRAILshort. Because the TRAIL pathway has been implicated in CD4 T cell death occurring during HIV-1 infection, we used short hairpin RNA knockdown, CRISPR deletion, or Abs specific for TRAILshort to determine the effect of inhibiting TRAILshort on the outcome of experimental acute HIV infection in vitro. Strikingly, all three approaches to TRAILshort deletion/inhibition enhanced HIV-induced death of both infected and uninfected human CD4 T cells. Thus, TRAILshort impacts T cell dynamics during HIV infection, and inhibiting TRAILshort causes more HIV-infected and uninfected bystander cells to die. TRAILshort is, therefore, a host-derived, host-adaptive mechanism to limit the effects of TRAIL-induced cell death. Further studies on the effects of TRAILshort in other disease states are warranted.


Asunto(s)
Apoptosis/genética , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/patología , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Anticuerpos/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , Línea Celular Tumoral , Supervivencia Celular , Técnicas de Inactivación de Genes , VIH-1/crecimiento & desarrollo , Humanos , Células Jurkat , Interferencia de ARN , ARN Interferente Pequeño/genética , Ligando Inductor de Apoptosis Relacionado con TNF/inmunología
5.
Am J Med ; 131(9): 1126-1129, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29605416

RESUMEN

BACKGROUND: Valvular involvement as a manifestation of Lyme carditis is rare. The first case describing a possible association between Lyme disease and cardiac valvular disease in the United States was published in 1993. Since that time there have been 2 cases of Lyme endocarditis confirmed by Borrelia-positive 16S ribosomal RNA polymerase chain reaction and sequencing from valvular tissue and reported from Europe. Here we describe a case of Lyme endocarditis that, to our knowledge, is the first reported case confirmed by molecular diagnostics in the United States. METHODS: We present the case of a 68-year-old man with progressive dyspnea who had mitral valve perforation with severe mitral valve insufficiency seen on transesophageal echocardiogram. RESULTS: Subsequently resected valve tissue had signs of acute inflammation without organisms seen. Although blood and valve tissue cultures were negative, 16S ribosomal RNA polymerase chain reaction and sequencing demonstrated Borrelia burgdorferi. CONCLUSION: Lyme endocarditis can be a challenging diagnosis to confirm, given the rarity of cases and the need for molecular tools of resected valve tissue. It should be included among diagnostic possibilities in patients with culture-negative endocarditis who have exposure to ticks in endemic and emerging areas of Lyme disease.


Asunto(s)
Endocarditis Bacteriana/microbiología , Enfermedad de Lyme/diagnóstico , Anciano , Borrelia burgdorferi/genética , Disnea/etiología , Endocarditis Bacteriana/diagnóstico , Humanos , Masculino , Insuficiencia de la Válvula Mitral/microbiología , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S
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