Imperial College London
Alternate

Dr Rob White

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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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

Citation

BibTex format

@unpublished{Szymula:2017:10.1101/176099,
author = {Szymula, A and Palermo, RD and Groves, IJ and Ba, abdullah M and Holder, BS and White, RE},
doi = {10.1101/176099},
title = {Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naive B cells, and facilitates recruitment of transcription factors to the viral genome},
url = {http://dx.doi.org/10.1101/176099},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:p>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.</jats:p><jats:p>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.</jats:p><jats:p>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 d
AU  - Szymula,A
AU  - Palermo,RD
AU  - Groves,IJ
AU  - Ba,abdullah M
AU  - Holder,BS
AU  - White,RE
DO  - 10.1101/176099
PY  - 2017///
TI  - Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naive B cells, and facilitates recruitment of transcription factors to the viral genome
UR  - http://dx.doi.org/10.1101/176099
ER  -
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