Viral and cellular regulation of immunometabolism
Nicholas Matheson is accepting applications for PhD students.
- Department of Medicine:
- MRC Clinician Scientist Fellow and Honorary Consultant
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.
helper T cells ; plasma membrane profiling ; host-pathogen interaction ; proteomics ; retrovirus ; immunobiology ; SILAC ; metabolism
Matheson NJ*, Greenwood EJD*, Wals K, Antrobus R, Williamson JC, Lehner PJ. Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants. eLife. 2016;5:e18296 * joint first authors
Matheson NJ, Greenwood EJD, Lehner PJL. Manipulation of immunometabolism by HIV – accessories to the crime? Curr Opin Virol. 2016;19:65-70
Matheson NJ, Sumner J, Wals K, Rapiteanu R, Weekes MP, Vigan R, Weinelt J, Schindler M, Antrobus R, Costa AS, Frezza C, Clish CB, Neil SJ, Lehner PJ. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell Host Microbe. 2015;18(4):409-23
Tchasovnikarova IA, Timms RT, Matheson NJ, Wals K, Antrobus R, Göttgens B, Dougan G, Dawson MA, Lehner PJ. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science. 2015;348(6242):1481-5
Matheson NJ, Peden AA, Lehner PJ. Antibody-Free Magnetic Cell Sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification. PLoS One. 2014;9(10):e111437