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J Virol, May 1998, p. 4015-4021, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Laura D. Strockbine,1 Jeffrey I. Cohen,2 Terry Farrah,1,dagger Stewart D. Lyman,1 Felecia Wagener,1 Robert F. DuBose,1 Richard J. Armitage,1 and Melanie K. Spriggs1,*

Immunex Corporation, Seattle, Washington 98101,1 and Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208922

Received 29 October 1997/Accepted 29 January 1998

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.

* Corresponding author. Mailing address: Molecular Biology, Immunex Corporation, 51 University St., Seattle, WA 98101. Phone: (206) 587-0430. Fax: (206) 624-7496. E-mail: spriggs{at}immunex.com.

dagger Present address: ZymoGenetics, Seattle, WA 98105.

J Virol, May 1998, p. 4015-4021, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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