Programme 3: Cellular Molecules Critical for Viral Replication

High-throughput screening for host targets influencing viral replication and drug susceptibility

Programme Co-ordinator: Prof Ari Fassati


Recent advances in genomics, proteomics, chemistry and automation allow the investigation of host-pathogens interactions on a global scale by high-throughput approaches. By creating an infrastructure to perform high-throughput screens we can:

  • Discover genes and molecules important for specific steps of the viral life cycle and their broader physiological functions
  • Identify cellular factors influencing viral fitness and ability to replicate in different hosts and cell types
  • Map druggable cellular targets required for viruses replication by chemical genetics
  • Select broadly cross-neutralizable epitopes for vaccine development
chemical structure

The identification of novel host factors necessary for virus replication or the host anti-viral response will expand our knowledge of both basic cellular mechanisms and how these are exploited by viruses. Furthermore, identification of such factors may provide potential targets for therapy that will be less sensitive to virus mutation than current antiviral drugs. Indeed, the only successful case of HIV-1 eradication has been achieved by eliminating the CCR5 co-receptor, a host factor, by bone marrow transplantation. Finally, discovering virus host-dependency factors and understanding their biological function and mapping broadly cross-neutralizable viral epitopes will provide the base knowledge for screenings to determine or predict susceptibility to specific virus infections, response to treatment and likelihood to develop drug resistance.


ari robot

The MRC has recently awarded to the Laboratory for Molecular and Cell Biology (LMCB) and the Wohl Virion Centre, UCL, a ~£2 million Translational Research Centre grant to set up a high-throughput screening and imaging facility. The Centre will be primarily based at the LMCB with one core facility within the category 3 labs of the Wohl Virion Centre, to perform screening work with human pathogenic viruses. This is currently the only facility of its kind in an academic environment in the UK. This facility will allow the screening of libraries of short hairpin RNA (shRNA), siRNAs, small compounds and antibodies against a diverse collection of viruses and primary cells.

The MRC Centre for Medical & Molecular Virology (CMMV) will interact closely with the MRC Translational Research Resource Centre (TRRC), which will provide essential infrastructure for imaging, data analysis, management and storage; the Centre of Biological and Medicinal Chemistry, UCL (Prof. David Selwood), which will provide access to one chemical library of ~30,000 diverse compounds, reformatting and curation services, chemi-informatics, virtual screening and support with focused libraries selection; The Department of Chemistry, UCL (Prof. Steve Caddick), which will provide novel synthetic compounds, not available to external organizations and help with compound optimization for target identification; the MRC Technology section (Dr. Justin Bryans), which will provide access to another chemical library and also links with industrial partners to help streamline commercially exploitable discoveries.

Use of infrastructure The infrastructure will be open to all members of the CM&MV and the TRC for work with viruses and the host response against them. It will also be accessible, on a cost-recovery basis, to the broader UCL community and to other academic institutions and biotech companies. A committee has been set up with members from the CMMV and TRRC Centre and the Departments of Chemistry and Medicinal Chemistry to streamline projects:

Dr Ariberto Fassati (CMMV)

Dr Robin Ketteler (Chair)(TRRC)

Dr Catherine Kettleborough (MRCT)

Prof Mark Marsh (TRRC)

Dr David Selwood (UCL LMCB)


  • Identification of druggable HIV-1 and HIV-2 host-dependency factors by chemical genetics (Ariberto Fassati)
  • Screening for host factors important for HIV latency (Richard Jenner, MRC CDF)
  • Screening for interferon-inducible HIV-1 restriction factors in human macrophages (Mahdad Noursadeghi, Greg Towers)
  • Screening for host factors important in HIV-1 egress from lymphocytic cells and the formation of the virological synapse (Clare Jolly)
  • High-throughput screening for host factors regulating latency and reactivation of KSHV and EBV (Paul Kellam)
  • High-throughput neutralisation assays to identify and characterise broadly neutralizing antibodies (Robin Weiss and Yasu Takeuchi)


Caddick, Prof Stephen

Fassati, Dr Ariberto

Jenner, Dr Richard

Jolly, Dr Clare

Kellam, Dr Paul

Ketteler, Dr Robin

Kettleborough, Dr Catherine

Marsh, Prof Mark

Noursadeghi, Dr Mahdad

Selwood, Dr David

Towers, Prof Greg

Weiss, Prof Robin

Takeuchi, Dr Yasu

Page last modified on 22 jun 12 11:51