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 or as a glycosylphosphatidylinositol-linked protein on the surfaces of transfected mammalian cells. To determine whether mammalian cells can be rendered susceptible to ALV-A infection by attaching a soluble form of TVA to their plasma membranes, the TVA-epidermal growth factor (EGF) fusion protein was generated. TVA-EGF is comprised of the extracellular domain of TVA linked to the mature form of human EGF. Flow cytometric analysis confirmed that TVA-EGF is a bifunctional reagent capable of binding simultaneously to cell surface EGF receptors and to an ALV-A surface envelope-Ig fusion protein. TVA-EGF prebound to transfected mouse fibroblasts expressing either wild-type or kinase-deficient human EGF receptors, rendered these cells highly susceptible to infection by ALV-A vectors. Viral infection was blocked specifically in the presence of a recombinant human EGF protein, demonstrating that the binding of TVA-EGF to EGF receptors was essential for infectivity. These studies have demonstrated that a soluble TVA-ligand fusion protein can mediate viral infection when attached to specific cell surfaces, suggesting an approach for targeting retroviral infection to specific cell types.
Snitkovsky
S
S
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Young
J A
JA
D000818:Animals; D001354:Avian Leukosis Virus / Q000502:physiology*; D030161:Avian Proteins; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D051379:Mice; D011991:Receptors, Virus / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
D030161:Avian Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C088745:Tva receptor; D004815:Epidermal Growth Factor