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The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein.
Biochem Soc Trans. 2008 Aug; 36(Pt 4):637-9.BS

Abstract

EBV (Epstein-Barr virus) alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and in the switch to the lytic cycle this epigenetic silencing is overturned. A key event is the activation of the viral protein Zta with three ZREs (Zta-response elements) from the BRLF1 promoter (referred to as Rp). Two of these ZREs contain CpG motifs and are methylated in the latent genome. Biochemical analyses and molecular modelling of Zta bound to methylated RpZRE3 indicate the precise contacts made between a serine and a cysteine residue of Zta with methyl cytosines. A single point mutant of Zta, C189S, is defective in binding to the methylated ZREs both in vitro and in vivo. This was used to probe the functional relevance of the interaction. ZtaC189S was not able to activate Rp in a B-cell line, demonstrating the relevance of the interaction with methylated ZREs. This demonstrates that Zta plays a role in overturning the epigenetic control of viral latency.

Authors+Show Affiliations

School of Life Sciences, University of Sussex, Brighton, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18631132

Citation

Karlsson, Questa H., et al. "The Reversal of Epigenetic Silencing of the EBV Genome Is Regulated By Viral bZIP Protein." Biochemical Society Transactions, vol. 36, no. Pt 4, 2008, pp. 637-9.
Karlsson QH, Schelcher C, Verrall E, et al. The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein. Biochem Soc Trans. 2008;36(Pt 4):637-9.
Karlsson, Q. H., Schelcher, C., Verrall, E., Petosa, C., & Sinclair, A. J. (2008). The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein. Biochemical Society Transactions, 36(Pt 4), 637-9. https://doi.org/10.1042/BST0360637
Karlsson QH, et al. The Reversal of Epigenetic Silencing of the EBV Genome Is Regulated By Viral bZIP Protein. Biochem Soc Trans. 2008;36(Pt 4):637-9. PubMed PMID: 18631132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein. AU - Karlsson,Questa H, AU - Schelcher,Celine, AU - Verrall,Elizabeth, AU - Petosa,Carlo, AU - Sinclair,Alison J, PY - 2008/7/18/pubmed PY - 2008/9/26/medline PY - 2008/7/18/entrez SP - 637 EP - 9 JF - Biochemical Society transactions JO - Biochem. Soc. Trans. VL - 36 IS - Pt 4 N2 - EBV (Epstein-Barr virus) alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and in the switch to the lytic cycle this epigenetic silencing is overturned. A key event is the activation of the viral protein Zta with three ZREs (Zta-response elements) from the BRLF1 promoter (referred to as Rp). Two of these ZREs contain CpG motifs and are methylated in the latent genome. Biochemical analyses and molecular modelling of Zta bound to methylated RpZRE3 indicate the precise contacts made between a serine and a cysteine residue of Zta with methyl cytosines. A single point mutant of Zta, C189S, is defective in binding to the methylated ZREs both in vitro and in vivo. This was used to probe the functional relevance of the interaction. ZtaC189S was not able to activate Rp in a B-cell line, demonstrating the relevance of the interaction with methylated ZREs. This demonstrates that Zta plays a role in overturning the epigenetic control of viral latency. SN - 0300-5127 UR - https://www.unboundmedicine.com/medline/citation/18631132/The_reversal_of_epigenetic_silencing_of_the_EBV_genome_is_regulated_by_viral_bZIP_protein_ L2 - https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST0360637 DB - PRIME DP - Unbound Medicine ER -