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Cambridge Immunology Network

Innate immune evasion by intracellular pathogens


Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects 60-90% of individuals. Following primary infection, HCMV establishes a latent infection under the control of a healthy immune system. Reactivation from viral latency to productive infection causes serious disease in immunocompromised individuals, such as transplant recipients and AIDS patients.


Our aim is to understand how human cytomegalovirus and other intracellular pathogens evade innate immunity. We combine cutting-edge tandem mass tag-based multiplexed proteomics with detailed molecular studies to focus on novel cellular targets.


We previously developed ‘Quantitative Temporal Viromics’ (QTV), a proteomic technique that provides a systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection. Applied to human cytomegalovirus infection, this technology provided a slew of novel data, detailing how HCMV orchestrates the expression of >8,000 cellular proteins to manipulate intrinsic, innate, and adaptive immune defences in addition to host signalling and metabolism (Science 2013; Cell 2014). A key question has been how to determine which of the >900 host proteins HCMV downregulates may have antiviral function. We have applied QTV to lytic Epstein Barr Virus lytic infection, in order to identify molecules commonly targeted by multiple viruses as a measure of importance (Ersing et al. Cell Reports 2017). We have also developed approaches to determine which viral gene targets a given host factor (eLife 2017) and have applied multiplexed proteomics to subcellular fractionation (Itzhak et al. Cell Reports 2017). Most recently, a key advance has been our development of three orthogonal screens to identify molecules not only downregulated but also proteasomally or lysosomally degraded by HCMV. These enabled us to identify the SWI/SNF ATPase helicase-like transcription factor as a key target of the HCMV protein UL145, and a novel antiviral restriction factor (Cell Host&Microbe 2018). Applying the same approach to vaccinia virus infection in collaboration with Professor Geoff Smith, we identified histone deacetylase 5 as another novel antiviral factor (Cell Reports 2019).


Our research currently focuses on the following areas:


Determining which proteins that are degraded by one or more viruses have antiviral function, then performing detailed molecular studies to determine the mechanism of action.

Development of innovative proteomic screens to identify new facets of innate immunity.

Application of our technology to study other intracellular pathogens, for example: Malaria (collaboration with Professor Manoj Duraisingh, Harvard School of Public Health); vaccinia virus (collaboration with Professor Geoff Smith, Department of Pathology, Cambridge); Herpes Simplex and BK viruses (collaboration with Dr Colin Crump, Department of Virology, Cambridge).


Key publications: 

Ravenhill BJ, Kanjee U, Ahouidi A, Nobre L, Williamson J, Goldberg JM, Antrobus R, Dieye T, Duraisingh MT, Weekes MP. Quantitative comparative analysis of human erythrocyte surface proteins between individuals from two genetically distinct populations. 2019. Commun Biol. 350:1-9.

Wei Wang L, Wang Z, Ersing I, Nobre L, Trudeau S, Zhao B, Weekes MP, Gewurz BE. Epstein-Barr Virus Subverts Mevalonate and Fatty Acid Pathways to Promote Infected B-cell Proliferation and Survival. 2019. Plos Pathogens. 15: 1-35.

Wang LW, Shen h, Nobre L, Ersing I, Paulo JA, Trudeau S, Sommermann T, Ma Y, Reinstadler B, Nomburg J, Cahir-McFarland E, Gygi SP, Mootha VK, Weekes MP*, Gewurz BE*. Epstein-Barr Virus Induced One-Carbon Metabolism Drives B-Cell Transformation. 2019. Cell Metabolism. doi: 10.1016/j.cmet.2019.06.003. *Joint last authorship.

Caller LG, Davies CTR, Antrobus R, Lehner PJ, Weekes MP*, Crump CM*. Temporal proteomic analysis of BK polyomavirus infection reveals virus-induced G2 arrest and highly effective evasion of innate immune sensing. 2019. J. Virol. 93:e00595-19 *Joint last authorship.

Soday L, Lu Y, Albarnaz JD, Antrobus R, Smith GL*, Weekes MP*. Quantitative temporal proteomic analysis of vaccinia virus infection reveals regulation of histone deacetylases by an interferon antagonist. 2019. Cell Reports. 7: 1920-1933. *Joint last authorship.

Nightingale K, Lin KM, Ravenhill B, Ruckova E, Davies C, Nobre L, Fielding CA, Fletcher-Etherington A, Soday L, Nichols H, Sugrue D, Wang ECY, Moreno P, Umrania Y, Antrobus R, Davison AJ, Wilkinson GWG, Stanton RJ , Tomasec P, Weekes MP. High definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms. 2018. Cell, Host & Microbe. 24:447-460.

Wang ECY, Pjechova M, Nightingale K, Vlahava V, Patel M, Ruckova E, Forbes S, Nobre L, Antrobus R, Roberts D, Fielding CA, Seirafian S, Davies J, Murrell I, Lau B, Wilkie GS, Suárez NM, Stanton RJ, Vojtesek B, Davison A, Lehner PJ, Weekes MP*, Wilkinson GWG*, Tomasec P*. Suppression of co-stimulation by human cytomegalovirus promotes evasion of cellular immune defences. 2018. PNAS. 115:4998-5003. *Joint last authors.

Itzhak DN, Davies C, Tyanova S, Mishra A, Williamson J, Antrobus R, Cox J, Weekes MP*, Borner GHH*. A Mass Spectrometry-Based Approach for Mapping Protein Subcellular Localization Reveals the Spatial Proteome of Mouse Primary Neurons. 2017. Cell Reports. 20:2706-2718. *Joint last authors

Ersing I, Nobre L, Wang LW, Soday L, Ma Y, Paulo JA, Narita Y, Ashbaugh CW, Jiang C, Grayson NE, Kieff E, Gygi SP, Weekes MP*, Gewurz BE*. A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells. 2017. Cell Reports. 19:1479-1493. *Joint last authors

Weekes MP, Tomasec P, Huttlin EL, Nusinow D, Stanton RJ, Fielding C, Murrell I, Wilkinson GWG, Lehner PJ, Gygi SP. Quantitative temporal viromics: a new approach to investigate host-pathogen interaction. 2014. Cell.157:1460-72.

Weekes MP, Tan SYL, Poole E, Talbot S, Antrobus R, Smith DL, Montag C, Gygi SP, Sinclair JH, Lehner PJ. Latency-associated degradation of the MRP1 drug transporter during latent Human Cytomegalovirus infection. 2013. Science. 340:199-202.


Other publications: 

For a complete list of publications, see:

Dr Michael  Weekes
Takes PhD students
Available for consultancy


Departments and institutes: 
Person keywords: 
immune evasion
host-pathogen interaction
innate immunity
mass spectrometry
viral restriction
viral immune evasion
DNA viruses