HIV and immunometabolism
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.
COVID-19 pandemic response
During the pandemic, we have applied our knowledge and skills in molecular virology to understanding and combating COVID-19. In particular, we have developed luminescent ‘reporter cells’, which emit light when they are infected with SARS-CoV-2. These allow us to test antiviral drugs, and measure ‘neutralising antibodies’ in blood samples from patients.
This work has led to numerous collaborations, such as the SARS-CoV-2 vaccine ResPonse In Obesity (SCoRPIO) study. One of five COVID-19 vaccine research projects funded by UK Research and Innovation, this will allow us to investigate the effect of obesity on COVID-19 vaccine effectiveness.
As a clinician scientist, Nick has also been closely involved with the pandemic response at Addenbrooke’s Hospital, and leads the Asymptomatic COVID-19 Screening Programme at the University of Cambridge. You can read more about this on the Stay Safe Cambridge Uni website, including how it was set up, the evidence it has worked, and the impact of mass testing for COVID-19 on the wider university sector.
Warne B, University of Cambridge Asymptomatic COVID-19 Screening Programme Consortium, Weekes MP†, McFarlane D†, Maxwell PH†, Matheson NJ†. Feasibility and efficacy of mass testing for SARS-CoV-2 in a UK university using swab pooling and PCR. Research Square. 2021. doi: 10.21203/rs.3.rs-520626/v1 †joint senior authors
Aggarwal D, The Cambridge COVID-19 Testing Centre, University of Cambridge Asymptomatic Screening Programme Consortium, COG-UK, Weekes MP†, Illingworth C†, Harrison EM†, Matheson NJ†, Goodfellow IG†. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission. Research Square. 2021. doi: 10.21203/rs.3.rs-520627/ †joint senior authors
Pereyra Gerber P, Duncan LM, Greenwood EJD, Marelli S, Naamati A, Teixeira-Silva A, Crozier TWM, Gabaev I, Zhan JR, Mulroney TE, Horner EC, Doffinger R, Willis AE, Thaventhiran JED, Matheson NJ. Protease-activatable biosensors of SARS-CoV-2 infection for cell-based drug, neutralisation and general virological assays. bioRxiv. 2021. doi: 10.1101/2021.03.22.435957
Matheson NJ, Warne B, Weekes MP, Maxwell PH. What have we learnt from mass testing for COVID-19 in universities? BMJ. 2021;375:n2388
Buckland MS, Galloway JB, Fhogartaigh CN, …, Lehner PJ†, Matheson NJ†, Thaventhiran JED†. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nat Commun. 2020;11(1):6385 †joint senior authors
Matheson NJ, Lehner PJ. How does SARS-CoV-2 cause COVID-19? Science. 2020;369(6503):510-1
Marelli S, Williamson JC, Protasio AV, Naamati A, Greenwood EJ, Deane JE, Lehner PJ, Matheson NJ. Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest. eLife. 2020;9:e53036
Javid B, Weekes MP, Matheson NJ. Covid-19: should the public wear face masks? BMJ. 2020;369:m1442
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