Novel gene sequencing approaches to understand immune dysfunction in HIV

HIV infection has a substantial impact on immune cells, and whilst many of these effects are improved after starting anti-HIV therapy, they are often not completely restored. People living with HIV therefore experience chronic inflammation and immune dysfunction that drives an increased risk of co-morbidities such as cancers, heart disease and neurocognitive impairment. Monocytes are a type of immune cell which are key mediators of inflammation and we have shown that monocytes from people with HIV have an altered look and function, including a heightened inflammatory state and an increased ability to drive processes which cause atherosclerosis and heart disease. Markers of monocyte dysfunction are associated with an increased risk of disease and death in people with HIV, so these observations are clinically relevant. To better understand why monocytes remain altered in people with HIV despite effective therapy, we are using exciting single cell RNA Sequencing technologies to thoroughly map changes to gene expression which may be driving these changes. The aim of this work is to identify novel therapeutic strategies to address immune dysfunction in people with HIV and prevent related disease and death. This work may also uncover mechanisms relevant to other chronic viral infections and indeed immune ageing, which show a similar pattern of monocyte changes. This project involves laboratory techniques including cell culture, immunophenotyping/flow cytometry, single cell RNA sequencing as well as bioinformatics and next generation sequencing analysis.