ESR 15: Uncovering how HIV hides in immune cells: metabolic reprogramming of CD4 T cells during infection – POSITION FILLED

PhD research

Host:

Dr. Jeroen den Dunnen

PI | Assistant Professor | PhD

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology

Experimental Immunology

Location AMC | K0-105 | Meibergdreef 9 1105 AZ Amsterdam

T: +31205668043  |  E: j.dendunnen@amsterdamumc.nl

Duration: 48 months

Background

Human immunodeficiency virus (HIV) causes a persistent infection that results in acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy was introduced in 1997 and has saved millions of lives by suppressing virus replication and preventing the development of AIDS. However, this therapy is not curative and has to be taken lifelong. Therefore, the goal of the international HIV research community now is to develop a lasting cure. The main obstacle for establishing a cure for HIV is the so-called viral reservoir. HIV is able to ‘hide’ in certain cells of infected individuals, where it persists despite decades of therapy. Characterization of the viral reservoir is thus central to HIV cure research. It has recently become clear that a family of receptors known as Fc receptors (FcRs) may contribute to the formation of the HIV reservoir. By combining the expertise of two groups, one on FcRs and the other one on HIV, we identified that FcRs indeed play a key role of HIV reservoir formation. The main focus of this project will be to unravel the responsible molecular mechanisms, in order to identify new avenues for therapeutic targeting of the viral reservoir.

Approach 

To identify the molecular mechanisms that underlie HIV reservoir formation, we will combine techniques of various different disciplines, including virology, molecular and cellular immunology, and (immuno)metabolism, such as CRISPR-Cas, RNA interference, flow cytometry, RNAseq, ChIPseq, Seahorse analysis, and fluxomics (a metabolomics technique). The project is divided in three key objectives. First, extensive characterization of the HIV reservoir by using our large patient cohort. Second, identification of the cell signaling and metabolic pathways that are essential for HIV reservoir formation. And third, inhibition of these key pathways by therapeutic inhibitors, in order to find new ways to deplete the HIV reservoir.

Our research team

The research team consists of two PI groups in the Amsterdam Medical Center (AMC) in Amsterdam. One group, led by dr. Jeroen den Dunnen of the Department of Rheumatology, who is an expert in the field of molecular immunology, particularly on signaling and metabolic reprogramming on immune cells by Fc receptors. The other group, led by prof. Ben Berkhout of the Department of Medical Microbiology, who is an expert in the field of HIV, particularly of HIV cure research and HIV reservoir formation. The complementary expertise of these two groups in this project will allow us to perform cutting-edge research at the cross-roads of immunology and virology.