EBV-positive human sera contain antibodies against the EBV BMRF-2 protein

We previously showed that the EBV glycoprotein BMRF-2 contains a functional integrin-binding Arg-Gly-Asp (RGD) domain that plays an important role in viral infection and cell-to-cell spread of progeny virions in oral epithelial cells. In this study, we found that EBV-seropositive human sera contain antibodies against BMRF-2. The inhibitory effect of EBV-positive sera on EBV infection of oral epithelial cells was substantially reduced by pre-incubation of serum samples with the BMRF-2 RGD peptide, suggesting that anti-BMRF-2 human antibodies possess neutralizing activity. EBV-specific sera reacted strongly with the BMRF-2 extracellular domain (170–213 aa) containing the RGD motif, whereas they reacted only weakly or not at all with a mutated form of the BMRF-2 extracellular domain containing AAA instead of RGD. These data indicate that RGD motif of BMRF-2 is part of an immunodominant antigenic determinant within the extracellular domain of BMRF-2 that may contribute to EBV neutralization during EBV reactivation.