Virus genomics

The Sanger Institute's Kellam laboratory researches host and virus intereaction, investigating virus genome variation and the metavirome.

Virus infections are one of the major causes of disease. Geographic locations of current infections of humans and other animals are visible through HealthMap.

[Wellcome Photo Library, Wellcome Images]

Background

Viruses that have been controlled in some countries through vaccination still cause devastating disease in other parts of the world. New virus diseases continue to emerge such as Human Immunodeficiency Virus (HIV) infection and viruses long linked with human disease such as Influenza continue to evolve causing new infections each year. The aim of the Virus genomics team is to understand how genetic changes in viruses and hosts influence the biological properties of viral pathogenesis, persistence and host susceptibility to infection.

Research

The Virus genomics team is determining genome diversity in RNA and DNA viruses utilising next generation sequencing technology. We are examining the viral metagenome in human and animal reservoirs and using RNAseq to investigate the patterns of gene expression and transcript processing dynamics in cells infected with human pathogenic viruses. This information is being harnessed through computational methods and data resources directed towards investigating host and viral genetic variation.

Figure 1

Figure 1
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We are interested to hear from post doctoral scientists wishing to pursue career development fellowships and undergraduates looking to pursue a PhD at the Wellcome Trust Sanger Institute.

Genetic variation influences all aspects of host and virus interactions; from the diversity in viral genomes in the 84 families of viruses currently defined by the International Committee on Taxonomy of Viruses (ICTV) to the cell type and species level differences in susceptibility to infection and disease (Fig 1).

Figure 2

Figure 2
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How viruses subvert host defences that have evolved to limit virus replication has been the focus of much virus research. Now with genome-scale views of host and virus gene expression programs during infection (Fig 2) and maps of viral protein interaction with the host we are now able to understand more about the consequences of virus and host genetic variation.

Selected Publications

  • Genome-wide innate immune responses in HIV-1-infected macrophages are preserved despite attenuation of the NF-kappa B activation pathway.

    Noursadeghi M, Tsang J, Miller RF, Straschewski S, Kellam P, Chain BM and Katz DR

    Journal of immunology (Baltimore, Md. : 1950) 2009;182;1;319-28

    PUBMED: 19109163; PMC: 2637478

  • Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection.

    Lopes AR, Kellam P, Das A, Dunn C, Kwan A, Turner J, Peppa D, Gilson RJ, Gehring A, Bertoletti A and Maini MK

    The Journal of clinical investigation 2008;118;5;1835-45

    PUBMED: 18398508; PMC: 2289792; DOI: 10.1172/JCI33402

  • X box binding protein XBP-1s transactivates the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF50 promoter, linking plasma cell differentiation to KSHV reactivation from latency.

    Wilson SJ, Tsao EH, Webb BL, Ye H, Dalton-Griffin L, Tsantoulas C, Gale CV, Du MQ, Whitehouse A and Kellam P

    Journal of virology 2007;81;24;13578-86

    PUBMED: 17928342; PMC: 2168861; DOI: 10.1128/JVI.01663-07

  • Genotyping Hepatitis B virus from whole- and sub-genomic fragments using position-specific scoring matrices in HBV STAR.

    Myers R, Clark C, Khan A, Kellam P and Tedder R

    The Journal of general virology 2006;87;Pt 6;1459-64

    PUBMED: 16690910; DOI: 10.1099/vir.0.81734-0

  • Infectogenomics: insights from the host genome into infectious diseases.

    Kellam P and Weiss RA

    Cell 2006;124;4;695-7

    PUBMED: 16497580; DOI: 10.1016/j.cell.2006.02.003

Team

No team members listed

* quick link - http://q.sanger.ac.uk/virusgen