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Journal of Virology, February 2002, p. 998-1003, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.998-1003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Phosphorylation of the Epstein-Barr Virus (EBV) DNA Polymerase Processivity Factor EA-D by the EBV-Encoded Protein Kinase and Effects of the L-Riboside Benzimidazole 1263W94

Edward Gershburg1 and Joseph S. Pagano1,2,3*

Lineberger Comprehensive Cancer Center,1 Departments of Medicine,2 Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 275993

Received 9 August 2001/ Accepted 19 October 2001

A member of the family of L-riboside benzimidazole compounds, 1263W94, was shown recently to inhibit replication of Epstein-Barr virus (EBV) (V. L. Zacny, E. Gershburg, M. G. Davis, K. K. Biron, and J. S. Pagano, J. Virol. 73:7271–7277, 1999). In the present report the effect of 1263W94 on the phosphorylation pattern of the EBV DNA polymerase processivity factor, EA-D, during viral reactivation in latently EBV-infected Akata cells is analyzed. This pattern specifically changes with progression of cytolytic infection. In the presence of 1263W94 the appearance of the hyperphosphorylated form of EA-D is mainly affected. Next, coexpression of the cloned EBV-encoded protein kinase (EBV PK), BGLF4, with EA-D demonstrated the ability of EBV PK to phosphorylate EA-D to its hyperphosphorylated form in transient assays. However, the phosphorylation of EA-D was not directly inhibited by 1263W94 in these coexpression assays. The results indicate that the EBV PK appears to be responsible for the hyperphosphorylation of EA-D, imply that the phosphorylation status of EA-D is important for viral replication, and suggest that 1263W94 acts at a level other than direct inhibition of EA-D phosphorylation by EBV PK.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295. Phone: (919) 966-1183. Fax: (919) 966-9673. E-mail: Joseph_Pagano{at}med.unc.edu.

Journal of Virology, February 2002, p. 998-1003, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.998-1003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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