The Epstein-Barr Virus BARF1 Gene Encodes a Novel, Soluble Colony-Stimulating Factor-1 Receptor

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with infectious mononucleosis and several tumors. The BARF1 gene is transcribed early after EBV infection from the BamHI A fragment of the EBV genome. Evidence shown here indicates that the BARF1 protein is secreted into the medium of transfected cells and from EBV-carrying B cells induced to allow lytic replication of the virus. Expression cloning identified colony-stimulating factor-1 (CSF-1) as a ligand for BARF1. Computer-assisted analyses indicated that subtle amino acid sequence homology exists between BARF1 and c-fms, the cellular proto-oncogene that is the receptor for CSF-1. Recombinant BARF1 protein was found to be biologically active, and it neutralized the proliferative effects of human 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.

EB病毒（Epstein-Barr virus，EBV）是一种普遍存在的疱疹病毒，与传染性单核细胞增多症及多种肿瘤密切相关。EB病毒基因组的BamHI A片段可在病毒感染后早期转录出BARF1基因。本研究展示的证据表明，BARF1蛋白可分泌至转染细胞的培养基中，同时也可从经诱导以支持病毒裂解复制的携带EB病毒的B细胞中分泌。通过表达克隆技术，研究人员鉴定出集落刺激因子1（colony-stimulating factor-1，CSF-1）是BARF1的配体。计算机辅助分析结果显示，BARF1与c-fms——一种作为CSF-1受体的细胞原癌基因——之间存在细微的氨基酸序列同源性。研究发现，重组BARF1蛋白具有生物学活性，在体外实验中可呈剂量依赖性方式中和人CSF-1的增殖效应。鉴于CSF-1是一种以对巨噬细胞的分化效应最为人熟知的多效性细胞因子，上述数据提示BARF1可能通过调节宿主对EB病毒感染的免疫应答发挥功能。