Jun 25, 2018

Paul Farrell

Paul Farrell (Imperial College London, United Kingdom)
–"EBV Genome Sequence Variation: Geography, Function and Disease"


J Virol. 2017 Jul 12;91(15). Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA.   (PubMed Link)
  • 138 new EBV genomes, 125 of these combined with 116 others = 241
  • Analysis of 241 aligned EBV genomes in multiple sequence alignment
  • Type1/Type2 variation and geographic
  • What genes harbour the variation
  • Genetic linkage in the EBV genome
  • Gp350, gp42
  • EBNA1
  • Codon usage
  • Heterogeneity
  • Chronic active EBV infection
  • Variation linked to NPC

  • Functional variation in EBV is related to disease
  • EBV genome deletions in BL (about 10% of African BL cell lines
  • Increase vBCL2 (BFRF1) expression from Wp
  • EBNA-3B as a tumor suppressor gene in EBV
  • E3B null is more tumorigeneic, DLBCL:

  • M81 EBV (Hong Kong NPC) has different properties from B95-8
  • More epithelial cell infection
  • EBVNA1 surviving binding
  • Chronic active EBV infection
    Sequenced saliva EBV from 8 cases (NIH)
  • No evidence of WZhet in saliva EBV genomes
  • Most heterogenous regions linked to NPC is Zp V3
    • SNPs in NPC Chinese vs Indonesia (27)
    • G155391A RPMS1 (Feng et al 2015, Wu et al 2018)
    • EBER2 (Wang e tal 2010)
    • ZpV3 (Tong et al 2003)


















  • Type differences in gp42
  • T1 and T2 differences also extends to Zp
  • T2 is not a good transforming virus unless change EBNA2!

- Additional BS69 binding site in type 2 EBNA2
- 28 days
- BS69 protein binds EBNA2 and can acts as trnascription repressor (binds to promoter motif)
- BS69 dimerization
  MYND/PELSP, PQLSP, PxLxP
  MYND/PILFPD/PFLPPSDWY
- PLoS Pathogens (2016, e1005414)


EBNA2-EBNA3 genetic linkage (241 EBV genomes)

  • EBNA2 T1 with EBNA3 T2 (212)
  • EBNA2 T2 with EBNA3 T2 ( 22)
  • EBNA2 T1 with EBNA3 T2 (  2)
  • EBNA2 T2 with EBNA3 T1 (  0)
  • Type 2 EBNA2 mutants work better with type 2 EBNA3


-miRNAs













EBNA1
- DNA replication
- plasmid maintence
- transcriptional enhancer
- NOX (ROS)
- USP7 (p53, MDM2)
- Survivin (apoptosis)





- differences in codon usage between latent (more uniform) than lytic genes (codon usages more variable)
- NKTLY97.1 contains a mixture of EBV genome, the major sequence is rearranged






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