JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01953-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Epstein-Barr viruses which express a CD21 antibody provide evidence that gp350's functions extend beyond B cell surface binding

Clemens Busse, Regina Feederle, Martina Schnölzer, Uta Behrends, Josef Mautner, and Henri-Jacques Delecluse^*

German Cancer Research Center, Heidelberg, Germany; Clinical Cooperation Group, Helmholtz Center Munich, Institute of Clinical Molecular Biology and Tumour Genetics and Children's Hospital, University of Technology, Munich, Germany

^* To whom correspondence should be addressed. Email: h.delecluse{at}dkfz.de.

The gp350 glycoprotein encoded by BLLF1 is crucial for efficient Epstein-Barr virus (EBV) infection of resting B cells. Gp350 binds to CD21 but whether this interaction sums up its functions remains unknown. We have generated gp350-null EBVs that display CD19-, CD21- or CD22-specific antibodies at their surface (designated as BLLF1-Ab). Gp350-complemented (BLLF1-C) and BLLF1-Ab were found to bind equally well to B cells. Surprisingly, BLLF1 binding was reduced only 1.7-fold relative to its complemented counterparts. Furthermore, B cells exposed to BLLF1-Ab or BLLF1 viruses presented structural antigens with comparable efficiency and achieved 25 to 80% of the T-cell activation elicited by BLLF1-C. These findings show that the gp350-CD21 interaction pair plays only a modest role during virus transfer to the endosomal compartment. However, primary B cells or Raji B cells infected with BLLF1-C viruses displayed a 35- to 70-fold higher infection rates than those exposed to BLLF1, BLLF1-CD22Ab or BLLF1-CD19Ab viruses. Complementation of the gp350 knock-out phenotype with CD21Ab substantially enhanced infection rates relative to BLLF1 but remained seven (Raji B cell line) to sixfold (primary B cells) less efficient than with gp350. We therefore infer that gp350 mainly exerts its functions after the internalization step, presumably during release of the viral capsid from the endosomal compartment, and that CD21-dependent but also CD21-independent molecular mechanisms are involved in this process. The latter appear to be characteristic of B cell infection as transfection of CD21 in 293 cells improved infection rates with both BLLF1-CD21Ab and BLLF1-C to a similar extent.