Core-binding factor influences the disease specificity of Moloney murine leukemia virus

The core site in the Moloney murine leukemia virus (Moloney MLV) enhancer w as previously shown to be an important determinant of the T-cell disease sp ecificity of the virus. Mutation of the core site resulted in a significant shift in disease specificity of the Moloney virus from: T-cell leukemia to erythroleukemia. We and others have since determined that a protein that b inds the core site, one of the core-binding factors (CBF) is highly express ed in thymus and is essential for hematopoiesis. Here we test the hypothesi s that CBF plays a critical role in mediating pathogenesis of Moloney MLV i n vivo. We measured the affinity of CBE for most core sites found in MLV en hancers, introduced sites with different affinities for CBF into the Molone y MLV genome, and determined the effects of these sites on viral pathogenes is. We found a correlation between CBF affinity and the latent period of di sease onset, in that Moloney MLVs with high-affinity CBF binding sites indu ced leukemia following a shorter latent period than viruses with lower-affi nity sites. The T-cell disease specificity of Moloney MLV also appeared to correlate with the affinity of CBF for its binding site. The data support a role for CBF in determining the pathogenic properties of Moloney MLV.