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Journal of Virology, April 2008, p. 4042-4051, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02436-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Deletion of Epstein-Barr Virus BFLF2 Leads to Impaired Viral DNA Packaging and Primary Egress as Well as to the Production of Defective Viral Particles{triangledown}

Marisa Granato,1,{dagger} Regina Feederle,2,{dagger} Antonella Farina,1 Roberta Gonnella,1 Roberta Santarelli,1 Birgit Hub,2 Alberto Faggioni,1 and Henri-Jacques Delecluse2*

Instituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Rome, Italy,1 Department of Virus Associated Tumors, German Cancer Research Center, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany2

Received 13 November 2007/ Accepted 7 February 2008

Previous genetic and biochemical studies performed with several members of the Alphaherpesvirus subfamily have shown that the UL31 and UL34 proteins are essential components of the molecular machinery that mediates the primary egress of newly assembled capsids across the nuclear membrane. Further, there is substantial evidence that BFLF2 and BFRF1, the respective positional homologs of UL31 and UL34 in the Epstein-Barr virus (EBV) genome, are also their functional homologs, i.e., that the UL31/UL34 pathway is common to distant herpesviruses. However, the low degree of protein sequence identity between UL31 and BFLF2 would argue against such a hypothesis. To further clarify this issue, we have constructed a recombinant EBV strain devoid of BFLF2 ({Delta}BFLF2) and show that BFLF2 is crucial for efficient virus production but not for lytic DNA replication or B-cell transformation. This defective phenotype could be efficiently restored by trans complementation with a BFLF2 expression plasmid. Detailed analysis of replicating cells by electron microscopy revealed that, as expected, {Delta}BFLF2 viruses not only failed to egress from the nucleus but also showed defective DNA packaging. Nonfunctional primary egress did not, however, impair the production and extracellular release of enveloped but empty viral particles that comprised L particles containing tegument-like structures and a few virus-like particles carrying empty capsids. The {Delta}BFLF2 and {Delta}UL31 phenotypes therefore only partly overlap, from which we infer that BFLF2 and UL31 have substantially diverged during evolution to fulfil related but distinct functions.

* 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.de

{triangledown} Published ahead of print on 20 February 2008.

{dagger} M.G. and R.F. contributed equally to this work.

Journal of Virology, April 2008, p. 4042-4051, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02436-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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