An interview with Professor Paul Farrell

June 2020

Professor Paul Farrell is based at Imperial College London, UK. In this interview, he tell us more about his research which focuses on the molecular biology of Epstein-Barr virus (EBV) and why this research is important to microbiology.

Paul Farrell
© Paul Farrell

Tells us more about your research.

I work on the molecular biology of Epstein-Barr virus (EBV), particularly how natural variation of the virus genome affects its biology and its role in human diseases. Most people are infected with EBV without symptoms, but EBV also causes infectious mononucleosis (glandular fever), several types of human cancer (lymphomas and carcinomas) and may contribute to multiple sclerosis. The incidence of these EBV associated diseases varies greatly in different parts of the world.

Why is this research important?

Our work is important for understanding the disease mechanisms, new approaches to early diagnosis and treatment of the cancers, and possible immunisation to prevent disease associated with EBV. In 1981, I became involved in the first sequencing of the 172kb genome of EBV. I brought analysis of the genetic content and gene expression to the sequencing team. Since then I have spent many years working out the genetic map and functions of some of the important viral genes.

Virologists often worry about whether they are working with the right strain of their virus. It was only recently that a new technique enabled us to sequence EBV directly from clinical samples. Now we have hundreds of EBV genome sequences, and we can make mutant viruses to analyse gene functions. This has given us an understanding of geographic variation and some indications of variants that are found more frequently in the cancers.

The cancer-associated EBV variation currently points to strains that may activate the virus replication program better or to certain deletions in the viral genome, which may alter the normal control of gene expression. There are also two main types of EBV (type 1 and type 2); we know some functional differences between these, but we are now trying to understand their in vivo significance.

I think immunisation could prevent infectious mononucleosis and some of the cancers associated with EBV; our knowledge of virus variation helps the current EBV vaccine projects. The new PCR-based diagnostic tests for early stage (i.e. treatable) nasopharyngeal carcinoma and current efforts to identify novel drugs that target specific EBV proteins in EBV-associated cancers also rely on our characterisation of the virus genes.

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