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Journal of Virology, November 2006, p. 10942-10949, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00907-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Multivalent Sequence Recognition by Epstein-Barr Virus Zta Requires Cysteine 171 and an Extension of the Canonical B-ZIP Domain{triangledown}

Pu Wang, Latasha Day, and Paul M. Lieberman*

The Wistar Institute, Philadelphia, Pennsylvania 19104

Received 3 May 2006/ Accepted 24 August 2006

Epstein-Barr virus (EBV) immediate-early protein Zta is a member of the basic-leucine zipper (B-ZIP) family of DNA binding proteins that has an unusual capacity to recognize multiple DNA recognition sites, including AP-1 and C/EBP binding sites. To better understand the structure and function of Zta, we have mutagenized cysteine residues within or adjacent to the B-ZIP domain. We found that serine substitution for cysteine 171 (C171S), which lies outside and amino terminal to the B-ZIP basic region, completely abrogates Zta capacity to initiate lytic cycle replication. C171S disrupted Zta transcription activation function of several EBV lytic cycle promoters, including the BMRF1 gene (EA-D) and the other lytic activator, Rta. Overexpression of Rta could not rescue the C171S defect for transcription reactivation or viral DNA replication. Zta C171S was defective for binding to these promoters in vivo, as measured by chromatin immunoprecipitation assay. Purified Zta C171S bound AP-1 sites similar to wild-type Zta, but it was incapable of binding several degenerate Zta sites, including a consensus C/EBP site. Zta truncation mutations reveal that residues N terminal to the B-ZIP (amino acids 156 to 178) confer C/EBP binding capacity to the otherwise AP-1-restricted DNA recognition function. Comparison among viral orthologues of Zta suggest that a conserved N-terminal extension of the consensus B-ZIP domain is required for this multivalent DNA recognition capacity of Zta and is essential for viral reactivation.

* Corresponding author. Mailing address: The Wistar Institute, 3601 Spruce St., Philadelphia, Pennsylvania 19104-4268. Phone: (215) 898-9491. Fax: (215) 898-0663. E-mail: lieberman{at}wistar.org.

{triangledown} Published ahead of print on 13 September 2006.

Journal of Virology, November 2006, p. 10942-10949, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00907-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wiedmer, A., Wang, P., Zhou, J., Rennekamp, A. J., Tiranti, V., Zeviani, M., Lieberman, P. M. (2008). Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication. J. Virol. 82: 4647-4655 [Abstract] [Full Text]  


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