A role for Epstein–Barr viral BALF1 in facilitating tumor formation and metastasis potential

Epstein–Barr virus (EBV) is a ubiquitous human herpesvirus that triggers transformation and tumorigenesis of latently infected B cells in vitro. BALF1, a Bcl-2-like EBV gene expressed in both latent and lytic stages, was recently characterized in EBV-infected cells; however, the role and function of BALF1 has remained elusive. Here, we demonstrate that BALF1 expression alters cellular morphology. Importantly, BALF1 promotes cellular transformation, with tumorigenicity assays showing larger and substantially greater numbers of tumors in BALF1 transfectant-injected mice compared to mice injected with pcDNA control transfectants. In addition, BALF1 expression increases cell survival under low-serum conditions, an effect that is attributable to suppression of apoptosis, not to promotion of cell-cycle progression. Furthermore, BALF1 transfectants exhibit markedly increased tumor metastasis in vitro and in vivo. Taken together, these findings suggest that BALF1 may be a new tumor marker for EBV diagnosis and provide a new direction for research on treatments of EBV-associated tumors.

► BALF1 alters cellular morphology. ► BALF1 promotes cellular transformation, larger and substantially greater numbers of tumors in mice. ► BALF1 expression increases cell survival under low-serum conditions, due to suppression of apoptosis, not to promotion of cell-cycle progression. ► BALF1 exhibits markedly increased tumor metastasis in vitro and in vivo. ► BALF1 may be a new tumor marker for EBV diagnosis and a new direction for research on treatments of EBV-associated tumors.