Paul Farrell, United Kingdom

Imperial College London Section of Virology
During his PhD in Cambridge, working with Tim Hunt and Richard Jackson, Paul Farrell discovered the phosphorylation of eIF-2 by PKR in response to dsRNA. As a post-doc at Yale with Peter Lengyel, he was the first to demonstrate a specific mRNA and protein induced by interferon. Returning to Cambridge, he applied transcription and RNA mapping methods to the Epstein-Barr virus genome, which was starting to be sequenced in Fred Sanger’s group. Farrell then helped to complete the B95-8 EBV genome sequence and interpretation of the EBV genetic map. Moving to London, he identified many of the EBV mRNAs including several novel spliced genes, (LMP2A and BZLF1). He showed that BZLF1 was a sequence specific DNA binding protein similar to the AP-1 transcription factor and characterised the early activation of the EBV lytic cycle by BZLF1. He identified cell genes that are regulated by EBNA2 and by the EBER RNAs and identified the growth regulatory roles of RUNX proteins in human B cells infected by EBV. Recently he has coordinated sequencing of a large collection of EBV genomes to understand natural variation of the viral genome, the mechanisms that cause type 1 EBV strains to immortalise human B cells more efficiently than type 2 EBV and likely roles for EBV genome sequence variation in human cancer. He is Professor of Tumour Virology at Imperial College London.

Presenter of 1 Presentation

 Conference Calendar
Plenary Session No Topic Needed

BIOLOGY OF EBV AND ITS RELATIONSHIP TO HUMAN CANCERS

Lecture Time
09:40 - 10:05
Presenter
Room
Bozar
Date
20.09.2019, Friday
Session Time
08:50 - 10:30
Presentation Topic
No Topic Needed

Abstract

Abstract Body

Epstein-Barr Virus (EBV) EBNA and LMP proteins and the viral miRNAs cause growth of infected human B lymphocytes, giving cells which resemble some lymphomas observed in immunodeficient patients. Infection of human T lymphocytes may also occur with some strains of EBV. EBV associated cancers in immunocompetent patients involve altered expression or mutation of cell genes in combination with some EBV gene functions. Immune evasion mechanisms play important roles in the normal virus life cycle and in cancers of immunocompetent patients.

The EBV genome can express over 100 gene products. After sequencing the EBV from many normal and cancer cell infections worldwide, we analysed a multiple sequence alignment of 241 EBV genomes. The largest variation is between type 1 and type 2 EBV, mediated by sequence difference in the EBNA2 and EBNA3 regions of the genome. Although type 1 EBV is much more effective at transforming B cells than type 2 EBV, both types can be involved in cancers. The greater ability of type 1 EBV to transform human B lymphocytes is partly due to a weaker interaction of type 1 EBNA2 with the cell BS69 protein. BS69 can obstruct the transcription factor activity of EBNA2. Searching for virus sequence variation that is linked to cancer development has identified a single nucleotide variation which creates an additional NFAT site in the promoter for the EBV BZLF1 virus replication activator. Strains with this variation activate virus replication more strongly and are enriched in EBV associated cancers.

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