Imperial College London

Dr Rob White

Faculty of MedicineDepartment of Medicine

Non-Clinical Lecturer in Virology
 
 
 
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Contact

 

+44 (0)20 7594 1124robert.e.white Website

 
 
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Location

 

308Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

35 results found

Bridges R, Correia S, Wegner F, Venturini C, Palser A, White RE, Kellam P, Breuer J, Farrell PJet al., 2019, Essential role of inverted repeat in Epstein–Barr virus IR-1 in B cell transformation; geographical variation of the viral genome, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 374, Pages: 20180299-20180299, ISSN: 0962-8436

JOURNAL ARTICLE

Correia S, Bridges R, Wegner F, Venturini C, Palser A, Middeldorp JM, Cohen JI, Lorenzetti MA, Bassano I, White RE, Kellam P, Breuer J, Farrell PJet al., 2018, Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and Diseases, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

JOURNAL ARTICLE

Styles CT, Paschos K, White RE, Farrell PJet al., 2018, The Cooperative Functions of the EBNA3 Proteins Are Central to EBV Persistence and Latency, PATHOGENS, Vol: 7, ISSN: 2076-0817

JOURNAL ARTICLE

Szymula A, Palermo RD, Bayoumy A, Groves IJ, Abdulla MB, Holder B, White REet al., 2018, Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naive B cells, and facilitates recruitment of transcription factors to the viral genome, PLOS PATHOGENS, Vol: 14, ISSN: 1553-7366

JOURNAL ARTICLE

Abdullah MMB, Palermo RD, Palser AL, Grayson NE, Kellam P, Correia S, Szymula A, White REet al., 2017, Heterogeneity of the Epstein-Barr Virus (EBV) Major Internal Repeat Reveals Evolutionary Mechanisms of EBV and a Functional Defect in the Prototype EBV Strain B95-8, JOURNAL OF VIROLOGY, Vol: 91, ISSN: 0022-538X

JOURNAL ARTICLE

Szymula A, Palermo R, Groves I, Ba abdullah M, Holder B, White Ret al., 2017, Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naive B cells, and facilitates recruitment of transcription factors to the viral genome.

The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it is reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated two sets of EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of IR1. Intronic mutations in the first of these knockouts suggested a role for the EBV sisRNAs in transformation. LPKOs with intact introns established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but umbilical cord B cells, and naive (IgD+, CD27-) adult B cells consistently died approximately two weeks after infection with LPKO, failing to establish LCLs. Quantitative PCR analysis of virus gene expression after infection identified both an altered ratio of the EBNA genes, and a dramatic reduction in transcript levels of both EBNA2-regulated virus genes (LMP1 and LMP2) and the EBNA2-independent EBER genes, particularly in the first 1-2 weeks. By 30 days post infection, these levels had equalised. In contrast, EBNA2-regulated host genes were induced efficiently by LPKO viruses. Chromatin immunoprecipitation revealed that recruitment of EBNA2 and the host factors EBF1 and RBPJ to all latency promoters tested was severely delayed, whereas these same factors were recruited efficiently to several host genes, some of which exhibited increased EBNA2 recruitment. We conclude that EBNA-LP does not simply co-operate with EBNA2 in activating gene transcription, but rather facilitates the recruitment of several transcription factors to the viral genome, to enable transcription of virus latency genes. Additionally, our findings suggest that different properties of EBV may have differing importance in transforming different B cell subsets.

WORKING PAPER

Styles CT, Bazot Q, Parker GA, White RE, Paschos K, Allday MJet al., 2017, EBV epigenetically suppresses the B cell-to-plasma cell differentiation pathway while establishing long-term latency, PLOS BIOLOGY, Vol: 15, ISSN: 1545-7885

JOURNAL ARTICLE

Correia S, Palser A, Karstegl CE, Middeldorp JM, Ramayanti O, Cohen JI, Hildesheim A, Fellner MD, Wiels J, White RE, Kellam P, Farrell PJet al., 2017, Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA, JOURNAL OF VIROLOGY, Vol: 91, ISSN: 0022-538X

JOURNAL ARTICLE

McHugh D, Caduff N, Barros MHM, Ramer PC, Raykova A, Murer A, Landtwing V, Quast I, Styles CT, Spohn M, Fowotade A, Delecluse H-J, Papoudou-Bai A, Lee Y-M, Kim J-M, Middeldorp J, Schulz TF, Cesarman E, Zbinden A, Capaul R, White RE, Allday MJ, Niedobitek G, Blackbourn DJ, Grundhoff A, Munz Cet al., 2017, Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression, CELL HOST & MICROBE, Vol: 22, Pages: 61-+, ISSN: 1931-3128

JOURNAL ARTICLE

Palser AL, Grayson NE, White RE, Corton C, Correia S, Abdullah MMB, Watson SJ, Cotten M, Arrand JR, Murray PG, Allday MJ, Rickinson AB, Young LS, Farrell PJ, Kellam Pet al., 2015, Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection, JOURNAL OF VIROLOGY, Vol: 89, Pages: 5222-5237, ISSN: 0022-538X

JOURNAL ARTICLE

Allday MJ, Bazot Q, White RE, 2015, The EBNA3 Family: Two Oncoproteins and a Tumour Suppressor that Are Central to the Biology of EBV in B Cells, EPSTEIN BARR VIRUS, VOL 2: ONE HERPES VIRUS: MANY DISEASES, Vol: 391, Pages: 61-117, ISSN: 0070-217X

JOURNAL ARTICLE

Skalska L, White RE, Parker GA, Turro E, Sinclair AJ, Paschos K, Allday MJet al., 2013, Correction: Induction of p16INK4a Is the Major Barrier to Proliferation when Epstein-Barr Virus (EBV) Transforms Primary B Cells into Lymphoblastoid Cell Lines., PLoS pathogens, Vol: 9, ISSN: 1553-7366

JOURNAL ARTICLE

Skalska L, White RE, Parker GA, Sinclair AJ, Paschos K, Allday MJet al., 2013, Induction of p16(INK4a) Is the Major Barrier to Proliferation when Epstein-Barr Virus (EBV) Transforms Primary B Cells into Lymphoblastoid Cell Lines, PLOS PATHOGENS, Vol: 9, ISSN: 1553-7374

JOURNAL ARTICLE

Paschos K, Parker GA, Watanatanasup E, White RE, Allday MJet al., 2012, BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV, NUCLEIC ACIDS RESEARCH, Vol: 40, Pages: 7233-7246, ISSN: 0305-1048

JOURNAL ARTICLE

White RE, Raemer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C, Savoldo B, Coutinho R, Boedoer C, Gribben J, Ibrahim HA, Bower M, Nourse JP, Gandhi MK, Middeldorp J, Cader FZ, Murray P, Muenz C, Allday MJet al., 2012, EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors, JOURNAL OF CLINICAL INVESTIGATION, Vol: 122, Pages: 1487-1502, ISSN: 0021-9738

JOURNAL ARTICLE

Yee J, White RE, Anderton E, Allday MJet al., 2011, Latent Epstein-Barr Virus Can Inhibit Apoptosis in B Cells by Blocking the Induction of NOXA Expression, PLOS ONE, Vol: 6, ISSN: 1932-6203

JOURNAL ARTICLE

Gregorovic G, Bosshard R, Karstegl CE, White RE, Pattle S, Chiang AKS, Dittrich-Breiholz O, Kracht M, Russ R, Farrell PJet al., 2011, Cellular Gene Expression That Correlates with EBER Expression in Epstein-Barr Virus-Infected Lymphoblastoid Cell Lines, JOURNAL OF VIROLOGY, Vol: 85, Pages: 3535-3545, ISSN: 0022-538X

JOURNAL ARTICLE

Nikitin PA, Yan CM, Forte E, Bocedi A, Tourigny JP, White RE, Allday MJ, Patel A, Dave SS, Kim W, Hu K, Guo J, Tainter D, Rusyn E, Luftig MAet al., 2010, An ATM/Chk2-Mediated DNA Damage-Responsive Signaling Pathway Suppresses Epstein-Barr Virus Transformation of Primary Human B Cells, CELL HOST & MICROBE, Vol: 8, Pages: 510-522, ISSN: 1931-3128

JOURNAL ARTICLE

White RE, Groves IJ, Turro E, Yee J, Kremmer E, Allday MJet al., 2010, Extensive Co-Operation between the Epstein-Barr Virus EBNA3 Proteins in the Manipulation of Host Gene Expression and Epigenetic Chromatin Modification, PLOS ONE, Vol: 5, ISSN: 1932-6203

JOURNAL ARTICLE

Skalska L, White RE, Franz M, Ruhmann M, Allday MJet al., 2010, Epigenetic Repression of p16(INK4A) by Latent Epstein-Barr Virus Requires the Interaction of EBNA3A and EBNA3C with CtBP, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366

JOURNAL ARTICLE

Paschos K, Smith P, Anderton E, Middeldorp JM, White RE, Allday MJet al., 2009, Epstein-Barr Virus Latency in B Cells Leads to Epigenetic Repression and CpG Methylation of the Tumour Suppressor Gene Bim, PLOS PATHOGENS, Vol: 5, ISSN: 1553-7366

JOURNAL ARTICLE

Macnab S, White R, Hiscox J, Whitehouse Aet al., 2008, Production of an infectious Herpesvirus saimiri-based episomally maintained amplicon system, JOURNAL OF BIOTECHNOLOGY, Vol: 134, Pages: 287-296, ISSN: 0168-1656

JOURNAL ARTICLE

Young P, Anderton E, Paschos K, White R, Allday MJet al., 2008, Epstein-Barr virus nuclear antigen (EBNA) 3A induces the expression of and interacts with a subset of chaperones and co-chaperones, JOURNAL OF GENERAL VIROLOGY, Vol: 89, Pages: 866-877, ISSN: 0022-1317

JOURNAL ARTICLE

Macnab S, White R, Hiscox J, Whitehouse Aet al., 2008, Production of an infectious herpesvirus saimiri-based episomally maintained amplicon system, 5th Annual Conference of the British-Society-for-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 416-416, ISSN: 1043-0342

CONFERENCE PAPER

Anderton E, Yee J, Smith P, Crook T, White RE, Allday MJet al., 2008, Two Epstein-Barr virus (EBV) oncoproteins cooperate to repress expression of the proapoptotic tumour-suppressor Bim: clues to the pathogenesis of Burkitt's lymphoma, ONCOGENE, Vol: 27, Pages: 421-433, ISSN: 0950-9232

JOURNAL ARTICLE

White RE, Carline L, Aday MJ, 2007, Mutagenesis of the herpesvirus saimiri terminal repeat region reveals important elements for virus production, JOURNAL OF VIROLOGY, Vol: 81, Pages: 6765-6770, ISSN: 0022-538X

JOURNAL ARTICLE

Amon W, White RE, Farrell PJ, 2006, Epstein-Barr virus origin of lytic replication mediates association of replicating episomes with promyelocytic leukaemia protein nuclear bodies and replication compartments, JOURNAL OF GENERAL VIROLOGY, Vol: 87, Pages: 1133-1137, ISSN: 0022-1317

JOURNAL ARTICLE

Calderwood M, White RE, Griffiths RA, Whitehouse Aet al., 2005, Open reading frame 73 is required for herpesvirus saimiri A11-S4 episomal persistence, JOURNAL OF GENERAL VIROLOGY, Vol: 86, Pages: 2703-2708, ISSN: 0022-1317

JOURNAL ARTICLE

Calderwood MA, White RE, Whitehouse A, 2004, Development of herpesvirus-based episomally maintained gene delivery vectors., Expert Opin Biol Ther, Vol: 4, Pages: 493-505, ISSN: 1471-2598

Successful gene therapy aims to deliver and express therapeutic genes to cure or slow the progression of disease. However, a major obstacle in the application of gene therapy has been the development of the vectors used to deliver heterologous DNA to the cell or tissue of choice. A number of viral- and non-viral-based vector systems have undergone clinical trials with varying success. However, at present, no vector system possesses the full complement of properties that are generally believed necessary in an ideal gene delivery system. Therefore, alongside attempts to improve current gene delivery vectors, the identification and evaluation of new viral vectors is crucial for the long-term success of gene therapy. Herpesviruses are large DNA viruses which possess a number of advantages as gene delivery vectors. These relate to an ability to package large DNA insertions and establish lifelong latent infections in which the genomic material exists as a stable episome. This review aims to highlight the potential of herpesvirus vectors, in particular an alternative vector system based on herpesvirus saimiri (HVS). HVS is capable of infecting a range of human cell lines with high efficiencies, and the viral genome persists as high copy number, circular, non-integrated episomes which segregate to progeny following cell division. This allows the virus-based vector to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Moreover, the insertion of a bacterial artificial chromosome cassette into the HVS genome simplifies the incorporation of large amounts of heterologous DNA for gene delivery. These properties offer characteristics similar to an artificial chromosome combined with an efficient delivery system and merit its continual development as a possible gene delivery vector for the future.

JOURNAL ARTICLE

White RE, Calderwood MA, Whitehouse A, 2003, Generation and precise modification of a herpesvirus salmiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence, JOURNAL OF GENERAL VIROLOGY, Vol: 84, Pages: 3393-3403, ISSN: 0022-1317

JOURNAL ARTICLE

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