DNA methylation analysis of PBMC from HIV and HIV/TB co-infected patients
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ABSTRACT: Genome wide DNA methylation profiling of PBMC from South African patients either infected with HIV only or coinfected with HIV and tuberculosis (TB). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles from PBMC samples. Samples included 19 HIV patients and 20 HIV/TB co-infected patients.
Project description:Genome wide DNA methylation profiling of PBMC from South African patients either infected with HIV only or coinfected with HIV and tuberculosis (TB). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles from PBMC samples. Samples included 19 HIV patients and 20 HIV/TB co-infected patients. Bisulphite converted DNA were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:Diagnosis of TB, especially in the presence of an HIV co-infection, can be challenging when using conventional diagnostic methods. In this study, we analyzed global gene expression data from PBMC of patients that were either mono-infected with HIV or co-infected with HIV and TB in order to identify a TB-specific gene signature. Total RNA obtained from PBMC from a South African cohort. Microarry analysis was performed to compare gene expression in patients either infected with HIV or co-infected with HIV/TB.
Project description:Diagnosis of TB, especially in the presence of an HIV co-infection, can be challenging when using conventional diagnostic methods. In this study, we analyzed global gene expression data from PBMC of patients that were either mono-infected with HIV or co-infected with HIV and TB in order to identify a TB-specific gene signature.
Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray Blood samples were collected during longitudinal observational studies of TB-IRIS patients and controls (both groups HIV-infected patients placed on antiretroviral treatment). PBMC were stimulated with heat killed H37Rv and RNA extracted.
Project description:RNA-sequencing was performed on baseline blood samples from HIV-infected and HIV-uninfected asymptomatic adults with recent household exposure to an index case of infectious pulmonary tuberculosis (TB) and with detectable Mtb DNA in PBMC. Additional sequencing was also performed on follow-up blood samples from HIV-infected participants following completion of isoniazid preventative therapy.
Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray
Project description:Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication in HIV-TB coinfected patients receiving combined antiretroviral therapy (cART). While monocytes/macrophages play major roles in both HIV- and TB-infection individually, a putative contribution of monocytes to the development of TB-IRIS remains unexamined. To investigate the possible functional contribution of monocytes to TB-IRIS pathogenesis, one of our first steps was to apply a genome-wide microarray analysis in monocytes of HIV-TB co-infected patients shortly after cART initiation. Based on the coparison of gene profiles between the TB-IRIS group and the control group, the modulated genes and pathways will be further investigated.
Project description:PolyA-RNA sequencing on Peripheral Blood Mononuclear Cells in patients infected with HIV and healthy donnors. Patients were effectively treated with cART (virological controlled and CD4+ T-cell counts over 500) for an extended period. HIV infected patients were not coinfected with HCV or HBV.
Project description:Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the most common coinfection among people living with HIV-1. This coinfection alters the efficacy of the immune response against both HIV-1 and Mtb, and is associated with accelerated HIV-1 disease progression and reduced survival. Enhanced HIV-1 replication in macrophages induced by Mtb coinfection may contribute to the worsened clinical outcomes observed in HIV-1/TB coinfected individuals. However, the impact of the HIV-1/TB coinfection on HIV-1 replication and latency in CD4+ T cells remains poorly studied. In this study, we used the acellular fraction of tuberculous pleural effusion (TB-PE) as a proxy for the microenvironment generated by Mtb infection. Using this physiologically relevant fluid, we investigated whether viral replication and HIV-1 latency in CD4+ T cells are affected by a TB-associated microenvironment. Interestingly, our results revealed that TB-PE shaped the transcriptional profile of CD4+ T cells impairing T cell receptor-dependent cell activation and decreased HIV-1 replication. Moreover, this immunosuppressive TB microenvironment promoted viral latency and inhibited HIV-1 reactivation in CD4+ T cells from people living with HIV-1. This study indicates that the immune response induced by TB may contribute to the persistence of the viral reservoir by silencing HIV-1 expression in individuals coinfected with both pathogens, allowing the virus to persist undetected by the immune system and increasing the size of the HIV-1 latent reservoir in cells at the site of the coinfection.