RETROVIRAL RETARGETING BY ENVELOPES EXPRESSING AN N-TERMINAL BINDING DOMAIN

We have engineered ecotropic Moloney murine leukemia virus-derived env elopes targeted to cell surface molecules expressed on human cells by the N-terminal insertion of polypeptides able to bind either Ram-1 pho sphate transporter (the first 208 amino acids of amphotropic murine le ukemia virus surface protein) or epidermal growth factor receptor (EGF R) (the 53 amino acids of EGF). Both envelopes were correctly processe d and incorporated into viral particles. Virions carrying these envelo pes could specifically bind the new cell surface receptors. Virions ta rgeted to Ram-1 could infect human cells, although the efficiency was reduced compared with that of virions carrying wild-type amphotropic m urine leukemia virus envelopes. The infectivity of virions targeted to EGFR was blocked at a postbinding step, and our results suggest that EGFR-bound virions were rapidly trafficked to lysosomes. These data su ggest that retroviruses require specific properties of cell surface mo lecules to allow the release of viral cores into the correct cell comp artment.