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Journal of Virology, May 2009, p. 4952-4962, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.00170-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Epstein-Barr Virus Alkaline Exonuclease BGLF5 Serves Pleiotropic Functions in Virus Replication{triangledown}

R. Feederle,1 H. Bannert,1 H. Lips,1 N. Müller-Lantzsch,2 and H.-J. Delecluse1*

German Cancer Research Center, Department of Virus Associated Tumours, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany,1 Department of Virology, Universitätsklinikum, Haus 47, 66421 Homburg/Saar, Germany2

Received 25 January 2009/ Accepted 24 February 2009

The Epstein-Barr virus (EBV) alkaline exonuclease BGLF5 has previously been recognized to contribute to immune evasion by downregulating production of HLA molecules during virus replication. We have constructed a BGLF5-null virus mutant to determine BGLF5's functions during EBV viral replication. Quantification of virus production in permissive 293 cells carrying a {Delta}BGLF5 genome identified a 17- to 21-fold reduction relative to complemented or wild-type controls. Detailed monitoring of {Delta}BGLF5 replication evidenced an impaired virus nucleocapsid maturation, a reduced primary egress and a 1.4-fold reduction in total viral DNA synthesis. {Delta}BGLF5 single-unit-length viral genomes were not only less abundant but also migrated faster than expected in gel electrophoresis. We concluded that BGLF5 pertained both to the generation and to the processing of viral linear genomes. {Delta}BGLF5 phenotypic traits were reminiscent of those previously identified in a mutant devoid of UL12, BGLF5's homolog in herpes simplex virus type 1, and indeed UL12 was found to partially complement the {Delta}BGLF5 phenotype. However, BGLF5-specific functions could also be identified; the nuclear membrane of replicating cells displayed images of reduplication and complex folding that could be completely corrected by BGLF5 but not UL12. Similar nuclear abnormalities were previously observed in cells transfected with BFLF2 and BFRF1, two viral proteins crucial for EBV nuclear egress. Interestingly, {Delta}BGLF5 cells produced more BFLF2 than wild-type or complemented counterparts. The present study provides an overview of BGLF5's functions that will guide future molecular studies. We anticipate that the 293/{Delta}BGLF5 cell line will be instrumental in such developments.

* Corresponding author. Mailing address: German Cancer Research Center, ATV-F100, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49-6221-424870. Fax: 49-6221-424852. E-mail: h.delecluse{at}dkfz-heidelberg.de

{triangledown} Published ahead of print on 4 March 2009.

Journal of Virology, May 2009, p. 4952-4962, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.00170-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Feederle, R., Mehl-Lautscham, A. M., Bannert, H., Delecluse, H.-J. (2009). The Epstein-Barr Virus Protein Kinase BGLF4 and the Exonuclease BGLF5 Have Opposite Effects on the Regulation of Viral Protein Production. J. Virol. 83: 10877-10891 [Abstract] [Full Text]  
  • Covarrubias, S., Richner, J. M., Clyde, K., Lee, Y. J., Glaunsinger, B. A. (2009). Host Shutoff Is a Conserved Phenotype of Gammaherpesvirus Infection and Is Orchestrated Exclusively from the Cytoplasm. J. Virol. 83: 9554-9566 [Abstract] [Full Text]  


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