Targeting HIV in macrophages to help achieve HIV cure

HIV remains a global health priority with approximately 39 million people currently living with HIV and 28 million of these on life-long anti-HIV therapy. 

HIV can persist in a reversibly latent state in infected cells despite effective treatment and viral replication can ‘rebound’ from these cells upon therapy-cessation, precluding HIV cure. 

While CD4+ T cells are a primary target of HIV in the blood, HIV also infects myeloid cells including macrophages in tissues. These reservoirs are an important source of resurgent HIV replication when therapy is stopped and can contribute to complications such as cardiovascular disease and neurocognitive impairment in people with HIV on therapy. Despite their importance, our knowledge of HIV infection outcomes in macrophages is incomplete and there is a dearth of knowledge regarding how HIV+ macrophages can be eliminated.

The objective of this work is to characterise HIV infection outcomes in different types of tissue macrophages and identify strategies to facilitate elimination to help achieve a HIV cure.

This exciting project will use a novel, primary cell model of latent HIV-infection in macrophages we have developed in combination with high content microscopy imaging to explore the following aims:

·       Identify agents which can sensitise HIV+ macrophages to cell death

·       Analyse latent HIV infection in different types of tissue macrophages.

·       Analyse novel single cell RNASeq data to characterise cellular processes driving latent HIV infection in macrophages and identify novel therapeutic targets.

Techniques involved: cell culture, immunophenotyping/flow cytometry, in vitro HIV infection, fluorescence microscopy, single cell RNAseq analysis/bioinformatics.