Emeritus ProfessorPaul Farrell, FMedSci
Emeritus Professor of Tumour Virology
Department of Infectious Disease - Faculty of Medicine
Orcid identifier0000-0002-6754-9351 (opens in a new tab)
- Emeritus Professor of Tumour VirologyDepartment of Infectious Disease - Faculty of Medicine
- 020 7594 2005 (Work)
- Imperial College London, Dept of Infectious Disease, Section of Virology, SAF Building, Exhibition Road, London, SW7 2AZ, United Kingdom
RESEARCH
Research
Download a copy of the EBV genetic map (link in side bar)
We have studied the mechanisms by which EBV causes human cells to grow, the role of the virus in human cancers and the regulation of the switch between latent persistence and virus replication. The virus proteins EBNA-1, EBNA-2, EBNA-3A, EBNA-3C, EBNA-LP and LMP-1 are required for EBV to cause permanent growth of human B lymphocytes and expression of the virus protein BZLF1 is the key switch from latency to the replicative cycle.
The unusual geographic distribution of some diseases associated with EBV links some natural variation of the virus genome with disease incidence. We analysed the sequences of many isolates of EBV from various parts of the world. EBV strains are classified as type 1 or type 2 based on their EBNA2 and EBNA3 sequences. Type 1 strains are much better at producing proliferating human B cell lines upon infection than type 2 strains. We developed a new assay for EBNA2 in cell proliferation that distinguishes a mechanism for this natural functional difference in EBV types. We also found that induction of the cell RUNX3 (AML-2) gene by EBNA2 is one of the key steps required for B cell proliferation.
Although EBV mainly infects B lymphocytes, we have now shown that some T lymphocytes from cord blood or young children (but not adults) can also be infected. Since infectious mononucleosis and multiple sclerosis are linked to primary infection of teenagers or adults, we are interested in the possibility that the additional T cell infection in infants somehow avoids that disease risk.
Download a copy of the EBV genetic map (link in side bar)
We have studied the mechanisms by which EBV causes human cells to grow, the role of the virus in human cancers and the regulation of the switch between latent persistence and virus replication. The virus proteins EBNA-1, EBNA-2, EBNA-3A, EBNA-3C, EBNA-LP and LMP-1 are required for EBV to cause permanent growth of human B lymphocytes and expression of the virus protein BZLF1 is the key switch from latency to the replicative cycle.
The unusual geographic distribution of some diseases associated with EBV links some natural variation of the virus genome with disease incidence. We analysed the sequences of many isolates of EBV from various parts of the world. EBV strains are classified as type 1 or type 2 based on their EBNA2 and EBNA3 sequences. Type 1 strains are much better at producing proliferating human B cell lines upon infection than type 2 strains. We developed a new assay for EBNA2 in cell proliferation that distinguishes a mechanism for this natural functional difference in EBV types. We also found that induction of the cell RUNX3 (AML-2) gene by EBNA2 is one of the key steps required for B cell proliferation.
Although EBV mainly infects B lymphocytes, we have now shown that some T lymphocytes from cord blood or young children (but not adults) can also be infected. Since infectious mononucleosis and multiple sclerosis are linked to primary infection of teenagers or adults, we are interested in the possibility that the additional T cell infection in infants somehow avoids that disease risk.
GRANTS
- GRANTImperial CoA MRCMedical Research Council (MRC)1 Sep 2020 - 1 Dec 2023