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The BDLF2/BMRF2 complex of EBV affects the cellular morphology

¹ UK Aachen;
² RWTH Aachen;
³ Fraunhofer Institute for Molecular Biology

⁴ E-mail: mkleines{at}ukaachen.de

Herpesvirus glycoproteins often form specific heterodimers which can fulfil functions that cannot be carried out by either of the partners acting alone. Here, we show that interactions between the Epstein-Barr virus (EBV) multi-span transmembrane envelope protein BMRF2 and type II membrane protein BDLF2 influence the way in which the proteins are trafficked in the cell, and hence the subcellular compartment in which they accumulate. When expressed transiently in mammalian cells, BDLF2 accumulates in the endoplasmic reticulum (ER), whereas BMRF2 accumulates in the ER and Golgi apparatus. However, when the two proteins are co-expressed, BDLF2 is transported with BMRF2 to the Golgi apparatus and from there to the plasma membrane, where the proteins co-localize extensively. The distribution of the two proteins at the plasma membrane was reproducibly associated with dramatic changes in cellular morphology, including the formation of enlarged membrane protrusions and cellular processes whose adhesion extremities were organized by the actin cytoskeleton. A dominant active form of the small GTPase RhoA was epistatic to this morphological phenotype, suggesting that RhoA is a central component of the signalling pathway which reorganizes the cytoskeleton in response to BDLF2/BMRF2. We conclude that EBV produces a glycoprotein heterodimer that induces changes in cellular morphology through reorganization of the actin cytoskeleton, and may facilitate virion spreading between cells.

Received 10 December 2008; accepted 18 February 2009.