Imperial College London
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ProfessorPaulFarrell

Faculty of Medicine, Department 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{Romero-Masters:2020:10.1371/journal.ppat.1008365,
author = {Romero-Masters, JC and Huebner, SM and Ohashi, M and Bristol, JA and Benner, BE and Barlow, EA and Turk, GL and Nelson, SE and Baiu, DC and Van, Sciver N and Ranheim, EA and Gumperz, J and Sherer, NM and Farrell, PJ and Johannsen, EC and Kenney, SC},
doi = {10.1371/journal.ppat.1008365},
journal = {PLoS Pathogens},
title = {B cells infected with Type 2 Epstein-Barr virus (EBV) have increased NFATc1/NFATc2 activity and enhanced lytic gene expression in comparison to Type 1 EBV infection},
url = {http://dx.doi.org/10.1371/journal.ppat.1008365},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Humans are infected with two distinct strains (Type 1 (T1) and Type 2 (T2)) of Epstein-Barr virus (EBV) that differ substantially in their EBNA2 and EBNA 3A/B/C latency genes and the ability to transform B cells in vitro. While most T1 EBV strains contain the “prototype” form of the BZLF1 immediate-early promoter (“Zp-P”), all T2 strains contain the “Zp-V3” variant, which contains an NFAT binding motif and is activated much more strongly by B-cell receptor signalling. Whether B cells infected with T2 EBV are more lytic than cells infected with T1 EBV is unknown. Here we show that B cells infected with T2 EBV strains (AG876 and BL5) have much more lytic protein expression compared to B cells infected with T1 EBV strains (M81, Akata, and Mutu) in both a cord blood-humanized (CBH) mouse model and EBV-transformed lymphoblastoid cell lines (LCLs). Although T2 LCLs grow more slowly than T1 LCLs, both EBV types induce B-cell lymphomas in CBH mice. T1 EBV strains (M81 and Akata) containing Zp-V3 are less lytic than T2 EBV strains, suggesting that Zp-V3 is not sufficient to confer a lytic phenotype. Instead, we find that T2 LCLs express much higher levels of activated NFATc1 and NFATc2, and that cyclosporine (an NFAT inhibitor) and knockdown of NFATc2 attenuate constitutive lytic infection in T2 LCLs. Both NFATc1 and NFATc2 induce lytic EBV gene expression when combined with activated CAMKIV (which is activated by calcium signaling and activates MEF2D) in Burkitt Akata cells. Together, these results suggest that B cells infected with T2 EBV are more lytic due to increased activity of the cellular NFATc1/c2 transcription factors in addition to the universal presence of the Zp-V3 form of BZLF1 promoter.
AU  - Romero-Masters,JC
AU  - Huebner,SM
AU  - Ohashi,M
AU  - Bristol,JA
AU  - Benner,BE
AU  - Barlow,EA
AU  - Turk,GL
AU  - Nelson,SE
AU  - Baiu,DC
AU  - Van,Sciver N
AU  - Ranheim,EA
AU  - Gumperz,J
AU  - Sherer,NM
AU  - Farrell,PJ
AU  - Johannsen,EC
AU  - Kenney,SC
DO  - 10.1371/journal.ppat.1008365
PY  - 2020///
SN  - 1553-7366
TI  - B cells infected with Type 2 Epstein-Barr virus (EBV) have increased NFATc1/NFATc2 activity and enhanced lytic gene expression in comparison to Type 1 EBV infection
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1008365
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000518637800042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008365
UR  - http://hdl.handle.net/10044/1/109211
VL  - 16
ER  -
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