The study of host-virus interactions has provided key insights into both viral pathogenesis and critical aspects of cell biology. To identify novel proteins and processes targeted by viruses, I use Stable Isotope Labelling by Amino Acids in Cell Culture (SILAC) and Tandem Mass Tag (TMT)-based functional proteomics to compare the expression of intracellular and cell surface proteins during viral infection.
Human Immunodeficiency Virus (HIV) infects almost 40 million people worldwide and causes more than 1 million AIDS-related deaths every year. In addition to the Gag, Pol and Env polyproteins common to all retroviruses, HIV encodes the so-called “accessory proteins” Vif, Vpr/Vpx, Nef and Vpu, dispensable for viral replication in vitro, but essential for viral pathogenesis in vivo.
Vpu and Nef are multifunctional adaptors which downregulate cell surface proteins. As well as their canonical substrates CD4, MHC-I and tetherin, I and others have discovered that they also target nutrient transporters to modulate the flux of metabolites across the plasma membrane of infected cells, such as amino acids and lipids.
Regulation of metabolism shapes the immune response, and my current work therefore aims to (1) understand the importance of the pathways manipulated by HIV for viral pathogenesis and T-cell immunobiology; and (2) identify new host factors manipulated by the virus. I also collaborate on proteomic experiments in a variety of other settings, including different viral infections and cancer.