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The virus host and virus genetics of severe influenza infection

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Paul Kellam, hosted by Stephen Bentley

Paul Kellam is the Viral Genomics group leader and Senior Investigator at the Wellcome Trust Sanger Institute and a Professor of Viral Pathogenesis at UCL . Paul has a degree in Microbiology from Reading University and a PhD investigating HIV drug resistance from the Wellcome Foundation laboratories and Imperial College, London. At the Wellcome Foundation, Paul’s research on HIV identified essential reverse transcriptase (RT) mutations conferring drug resistance to zidovudine (AZT) leading to determining how the combinatorial development of multiple mutations leads to high-level resistance to antiviral drug regimes. This also led to the first use of capillary sequencing of HIV to detect minority drug resistance variants in patients. In 1996 Paul joined Robin Weiss’s laboratory at the Institute of Cancer Research to work on Kaposi’s sarcoma associated herpesvirus (KSHV). There Paul’s KSHV research identified the virus Latent Nuclear Antigen (LANA) and developed a monoclonal antibody to LANA that is marketed worldwide, being used for the identification of KSHV latently infected cells. This antibody was used to show definitively that KSHV is associated with all forms of Kaposi’s sarcoma, Primary Effusion Lymphoma (PEL) and a plasmablastic variant of Multicentric Castleman’s disease. Paul’s laboratory developed the first KSHV gene expression microarray to explore virus lytic replication and pioneered the use of virus bioinformatics and host gene expression arrays to characterise herpesvirus driven B-cell tumours. This identified the B-cell differentiation transcription factor, X-box binding protein-1 (XBP-1) as the host transcription factor that switches KSHV from latency to the virus lytic cycle. In 2009 Paul established the Virus Genomics laboratory at the Wellcome Trust Sanger Institute which investigates genetic variation of host and virus to determine the molecular and pathogenic outcomes of virus infections. In particular the laboratory uses next generation sequencing of virus and human genomes in people infected with HIV , influenza virus, norovirus, and human herpesviruses. Recently, we identified the first human influenza disease severity determining allele, IFITM3 in people hospitalised with pandemic influenza A H1N1 . Paul’s laboratory combines molecular biology and virology with computational research to address basic biological questions in infection and immunity and has worked closely with the Kingdom of Saudi Arabia in characterising the genetics of MERS -CoV.

This talk is part of the Immunology and Medicine Seminars series.

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