THE EPSTEIN-BARR-VIRUS BARF1 GENE ENCODES A NOVEL, SOLUBLE COLONY-STIMULATING FACTOR-I RECEPTOR

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with i nfectious mononucleosis and several tumors. The BARF1 gene is transcri bed early after EBV infection from the BamHI A fragment of the EBV gen ome. Evidence shown here indicates that the BARF1 protein is secreted into the medium of transfected cells and from EBV-carrying B cells ind uced to allow lytic replication of the virus. Expression cloning ident ified colony-stimulating factor-1 (CSF-1) as a ligand for BARF1, Compu ter-assisted analyses indicated that subtle amino acid sequence homolo gy exists between BARF1 and c-fms, the cellular proto-oncogene that is the receptor for CSF-1. Recombinant BARF1 protein was found to be bio logically active, and it neutralized the proliferative effects of huma n CSF-1 in a dose-dependent fashion when assayed in vitro. Since CSF-1 is a pleiotropic cytokine best known for its differentiating effects on macrophages, these data suggest that BARF1 may function to modulate the host immune response to EBV infection.