Targeting HIV-infected macrophages to facilitate HIV cure

Anti-HIV therapy suppresses HIV replication and prevents AIDS. However, HIV currently cannot be cured and continuous life-long therapy is required. HIV cure is possible, but extremely challenging, and a much better understanding of mechanisms that govern maintenance and elimination of HIV-infected cells is required to achieve this goal.

HIV can persist in a reversibly latent state in infected cells despite treatment and viral replication ‘rebounds’ upon therapy-cessation, precluding HIV cure. While CD4+ T cells contain most of this latent reservoir in blood, HIV also infects myeloid cells including macrophages in tissues and these reservoirs are an important, clinically relevant source of resurgent HIV replication when therapy is stopped. Despite their importance, HIV cure strategies rarely consider HIV-infected macrophages and there is a dearth of knowledge regarding this reservoir and how it can be eliminated.

The overall objective of this work is to identify strategies to target latently-infected HIV+ macrophages and facilitate their elimination by the immune system 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 our lab to explore some of the following aims:

• identify agents which can sensitise HIV+ macrophages to cell death
• analyse latent HIV infection in different macrophage subtypes (gut, lung, others)
• use novel single cell RNASeq technology 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 (under PC3 conditions), fluorescence microscopy, single cell RNA Sequencing.