Evolution has produced an ‘arms race’ between viruses and the cells they infect. Studying host-virus interactions therefore provides key insights into both viral pathogenesis and cell biology, and suggests novel therapeutic approaches.
To discover processes and pathways targeted by viruses, we use Stable Isotope Labelling by Amino Acids in Cell Culture (SILAC) and Tandem Mass Tag (TMT)-based functional proteomics to characterise changes in intracellular and cell surface proteins during viral infection.
Human Immunodeficiency Virus (HIV) infects almost 40 million people worldwide and causes approximately 1 million AIDS-related deaths every year. We have identified dysregulation of hundreds of proteins in HIV-infected T cells, including cell surface amino acid transporters.
Amino acid metabolism is increasingly recognised to shape the immune response, and our current research therefore aims to (1) understand the importance of the pathways regulated by HIV for viral pathogenesis and T cell immunobiology, and (2) identify new host factors targeted by the virus.
As well as amino acid transport, we have broad expertise in manipulating and analysing primary human CD4+ T cells, and collaborate on experiments in proteomics and metabolism in other related settings, including different viral infections and cancer.
Greenwood EJD, Williamson JC, Sienkiewicz A, Naamati A, Matheson NJ, Lehner PJ. Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection. Cell Rep. 2019; 27, 1579-96
Naamati A, Williamson JC, Greenwood EJD, Marelli S, Lehner PJ, Matheson NJ. Functional proteomic atlas of HIV infection in primary human CD4+ T cells. eLife. 2019; 8, e41431
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, 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, 1481-1485
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, e111437