Epstein-Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells

The Epstein-Barr virus (EBV) BARF1 gene encodes a soluble colony-stimulatin g factor 1 (CSF-1) receptor that neutralizes the effects of CSF-1 in vitro. To study the effect of BARF1 on EBV-induced transformation, we added recom binant BARF1 to B cells in the presence of EBV. BARF1 did not enhance trans formation of B cells by EBV in vitro. To study the role of BARF1 in the con text of EBV infection, we constructed a recombinant EBV mutant with a large deletion followed by stop codons in the BARF1 gene as well as a recombinan t virus with a wild-type BARF1 gene. While BARF1 has previously been shown to act as an oncogene in several cell lines, the EBV BARF1 deletion mutant transformed B cells and initiated latent infection, and the B cells transfo rmed with the BARF1 mutant virus induced tumors in SCID mice with an effici ency similar to that of the wild-type recombinant virus. Since human CSF-1 stimulates secretion of alpha interferon from mononuclear cells and BARF1 e ncodes a soluble CSF-1 receptor, we examined whether recombinant BARF1 or B ARF1 derived from EBV-infected B cells could inhibit alpha interferon secre tion. Recombinant BARF1 inhibited alpha interferon secretion by mononuclear cells in a dose-dependent fashion. The B cells transformed with mutant BAR F1 EBV showed reduced inhibition of alpha interferon secretion by human mon onuclear cells when compared with the B cells transformed with wild-type re combinant virus. These experiments indicate that BARF1 expressed from the E BV genome directly inhibits alpha interferon secretion, which may modulate the innate host response to the virus.