Imperial College London

ProfessorPaulFarrell

Faculty of MedicineDepartment of Infectious Disease

Professor of Tumour Virology
 
 
 
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Contact

 

+44 (0)20 7594 2005p.farrell Website

 
 
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Location

 

Section of VirologyNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cancian:2011:10.1371/journal.ppat.1002164,
author = {Cancian, L and Bosshard, R and Lucchesi, W and Karstegl, CE and Farrell, PJ},
doi = {10.1371/journal.ppat.1002164},
journal = {PLoS Pathog},
title = {C-terminal region of EBNA-2 determines the superior transforming ability of type 1 Epstein-Barr virus by enhanced gene regulation of LMP-1 and CXCR7.},
url = {http://dx.doi.org/10.1371/journal.ppat.1002164},
volume = {7},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Type 1 Epstein-Barr virus (EBV) strains immortalize B lymphocytes in vitro much more efficiently than type 2 EBV, a difference previously mapped to the EBNA-2 locus. Here we demonstrate that the greater transforming activity of type 1 EBV correlates with a stronger and more rapid induction of the viral oncogene LMP-1 and the cell gene CXCR7 (which are both required for proliferation of EBV-LCLs) during infection of primary B cells with recombinant viruses. Surprisingly, although the major sequence differences between type 1 and type 2 EBNA-2 lie in N-terminal parts of the protein, the superior ability of type 1 EBNA-2 to induce proliferation of EBV-infected lymphoblasts is mostly determined by the C-terminus of EBNA-2. Substitution of the C-terminus of type 1 EBNA-2 into the type 2 protein is sufficient to confer a type 1 growth phenotype and type 1 expression levels of LMP-1 and CXCR7 in an EREB2.5 cell growth assay. Within this region, the RG, CR7 and TAD domains are the minimum type 1 sequences required. Sequencing the C-terminus of EBNA-2 from additional EBV isolates showed high sequence identity within type 1 isolates or within type 2 isolates, indicating that the functional differences mapped are typical of EBV type sequences. The results indicate that the C-terminus of EBNA-2 accounts for the greater ability of type 1 EBV to promote B cell proliferation, through mechanisms that include higher induction of genes (LMP-1 and CXCR7) required for proliferation and survival of EBV-LCLs.
AU - Cancian,L
AU - Bosshard,R
AU - Lucchesi,W
AU - Karstegl,CE
AU - Farrell,PJ
DO - 10.1371/journal.ppat.1002164
PY - 2011///
TI - C-terminal region of EBNA-2 determines the superior transforming ability of type 1 Epstein-Barr virus by enhanced gene regulation of LMP-1 and CXCR7.
T2 - PLoS Pathog
UR - http://dx.doi.org/10.1371/journal.ppat.1002164
UR - https://www.ncbi.nlm.nih.gov/pubmed/21857817
UR - http://hdl.handle.net/10044/1/21221
VL - 7
ER -