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Journal of Virology, May 2009, p. 4616-4623, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.01613-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Primary B-Cell Infection with a {Delta}BALF4 Epstein-Barr Virus Comes to a Halt in the Endosomal Compartment yet Still Elicits a Potent CD4-Positive Cytotoxic T-Cell Response{triangledown}

Bernhard Neuhierl,1,§ Regina Feederle,1,§ Dinesh Adhikary,2 Birgit Hub,1 Karsten Geletneky,3 Josef Mautner,2 and Henri-Jacques Delecluse1*

German Cancer Research Center, Department of Virus Associated Tumours, Heidelberg, Germany,1 Clinical Cooperation Group, Children's Hospital, Hematology-Oncology, Technical University Munich, Munich, Germany,2 Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany3

Received 29 July 2008/ Accepted 16 February 2009

Epstein-Barr virus (EBV) infection is mediated by several viral envelope glycoproteins. We have assessed gp110's functions during the virus life cycle using a mutant that lacks BALF4 ({Delta}BALF4). Exposure of various cell lines and primary cell samples of epithelial or lymphoid lineages to the {Delta}BALF4 mutant failed to establish stable infections. The {Delta}BALF4 virus, however, did not differ from wild-type EBV in its ability to bind and become internalized into primary B cells, in which it elicited a potent T-cell-specific immune reaction against virion constituents. These findings show that {Delta}BALF4 viruses can reach the endosome-lysosome compartment and dovetail nicely with the previously identified contribution of gp110 to virus-cell fusion. Other essential steps of the virus life cycle were unaffected in the viral mutant; DNA lytic replication and viral titers were not altered in the absence of gp110, and {Delta}BALF4 viruses complemented in trans transformed infected B cells with an efficiency indistinguishable from that observed with wild-type viruses. All of the steps of virus maturation could be observed in lytically induced 293/{Delta}BALF4 cells. Induction of lymphoblastoid cells generated with transiently complemented {Delta}BALF4 virus led to the production of rare mature virions. We therefore infer that gp110 is not required for virus maturation and egress in 293 cells or in B cells. The {Delta}BALF4 virus's phenotypic traits, an inability to infect human cells coupled with potent antigenicity, potentially qualify this mutant as a live vaccine. It will provide a useful tool for the detailed study of EBV-cell interactions in a physiological context.

* 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 25 February 2009.

§ Both authors contributed equally to this work.

Journal of Virology, May 2009, p. 4616-4623, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.01613-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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