CELL-SPECIFIC VIRAL TARGETING MEDIATED BY A SOLUBLE RETROVIRAL RECEPTOR-LIGAND FUSION PROTEIN

TVA, the cellular receptor for subgroup A avian leukosis viruses (ALV- A) can mediate viral entry when expressed as a transmembrane protein o r as a glycosylphos phatidylinositol-linked protein on the surfaces of transfected mammalian cells. To determine whether mammalian cells tan be rendered susceptible to ALV-A infection by attaching a soluble for m of TVA to their plasma membranes, the TVA-epidermal growth factor (E GF) fusion protein was generated. TVA-EGF is comprised of the extracel lular domain of TVA Linked to the mature form of human EGF, Flow cytom etric analysis confirmed that TVA-EGF is a bifunctional reagent capabl e of binding simultaneously to cell surface EGF receptors and to an AL V-A surface envelope-Ig fusion protein. TVA-EGF prebound to transfecte d mouse fibroblasts expressing either wild-type or kinase-deficient hu man EGF receptors, rendered these cells highly susceptible to infectio n by ALV-A vectors. Viral infection was blocked specifically in the pr esence of a recombinant human EGF protein, demonstrating that the bind ing of TVA-EGF to EGF receptors was essential for infectivity, These s tudies have demonstrated that a soluble TVA-ligand fusion protein can mediate viral infection when attached to specific cell surfaces, sugge sting an approach for targeting retroviral infection to specific cell types.