The disclosure provides methods and compositions for identifying agents
that inhibit a neoplastic cellular phenotype mediated by the NS4B protein
nucleotide binding motif (NBM) of hepatitis C virus (HCV). In general,
the methods involve contacting a candidate agent with a mammalian cell
expressing an NS4B NBM polypeptide of an HCV virus, wherein expression of
the NS4B NBM polypeptide in the absence of candidate agent promotes a
neoplastic cellular phenotype, and detecting the presence or absence of
an effect of said candidate agent on NS4B-mediated promotion of a
neoplastic cellular phenotype. The disclosed methods and compositions
find use in a variety of therapeutic and screening applications.