Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.
Project description:To understand how HIV and timing of ART initiation affect the transcriptional profile of Mtb-specific CD4 T cells, we performed 10X single-cell RNA sequencing comparing Mtb-specific CD4 T cell transcriptomes from people without HIV, people with HIV prior to ART, and people with HIV after ART from the Mombasa Cohort in Mombasa, Kenya. PBMCs were stimulated overnight with Mycobacterium tuberculosis whole cell lysate and CD40L+CD69+ Mtb-specifc CD4 T cells were sorted for sequencing.
Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).
Project description:<p>Objective: The gut microbiome plays a pivotal role in human immunodeficiency virus (HIV) infection. However, the associated alterations in the gut microbiome-host interaction remain unclear. This study aims to investigate the gut microbiota and fecal metabolites in people living with HIV (PLWH).</p><p>Method: We collected stool samples from 70 PLWH and 34 healthy controls (HCs) and performed 16S rRNA gene sequencing. Metabolite analysis was conducted using liquid chromatography-mass spectrometry.</p><p>Results: Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the most abundant phyla in both groups. At the genus level, Escherichia Shigella was significantly upregulated in the PLWH group, whereas Bacteroides were upregulated in the HC group. Functional prediction of the microbiota indicated significant reductions in alanine, aspartate, and glutamate metabolism, as well as histidine metabolism. Furthermore, comparison of fecal metabolites between the HC and PLWH groups identified 38 differentially abundant metabolites across four enriched human metabolic pathways. Spearman correlation analysis revealed close relationships between four differentially abundant microbiota members and five differentially abundant fecal metabolites, which may influence specific human metabolic pathways.</p><p>Conclusion: Our findings provide a foundation for further experimental investigations into the contribution of the gut microbiota and its associated metabolites to HIV/AIDS, offering a novel perspective for future studies on HIV/AIDS.</p>
Project description:Background: Although acquired immunodeficiency syndrome-related mortality has decreased since the introduction of antiretroviral therapy, the incidence of lung cancer in patients living with HIV (PLWH) remains high. Understanding the effects of tobacco smoke on airway gene expression in PLWH may provide insight into the elevated lung cancer risk associated with HIV. Methods: Airway epithelial brushings were collected from 12 PLWH who smoke and 19 PLWH who have never smoked and profiled using RNA-seq. Linear models were used to identify genes differentially expressed between people who smoke and have never smoked and between people who previously smoked and have never smoked. Gene set enrichment analysis was used to validate smoking-related gene signatures across datasets. Data was integrated with gene expression data from a cohort of patients without HIV to identify genes differentially modulated by both smoking and HIV status. Results: We found that previous smoking-related gene signatures are similarly associated with smoking in PLWH, including the persistent differential expression of a subset of "irreversibly altered" genes in people who previously smoked compared to people who have never smoked. We also identified and validated two gene signatures specifically modulated in people who smoke without HIV. Conclusions: Many of the effects of smoking on bronchial gene expression are shared between PLWH and non-HIV individuals. Of the subset of genes that differ between PLWH and non-HIV individuals, it appears that the effect of smoking on gene expression is more attenuated in PLWH. This includes genes related to oxidative stress and epithelial integrity, and suggests potential mechanisms that may contribute to smoking-related outcomes that are more prevalent in PLWH, such as lung cancer.
Project description:People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
Project description:Genome-wide DNA methylation profiling of blood samples from people living with HIV HIV-1 infection impacts biological ageing, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating sex differences in clinical, immunological, and virological measures, females have been underrepresented in most HIV epigenetic studies. Hence, we generated a more representative epigenetic dataset to examine sex differences in epigenetic ageing and relationships to clinical phenotypes.