TARGETED INFECTION OF HUMAN-CELLS VIA MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES BY MOLONEY MURINE LEUKEMIA VIRUS-DERIVED VIRUSES DISPLAYING SINGLE-CHAIN ANTIBODY FRAGMENT-ENVELOPE FUSION PROTEINS

As an approach to cell targeting by retroviruses, the lack of which co nstitutes one major limitation of retroviral vector technology, we eng ineered the Moloney murine leukemia virus ecotropic envelope glycoprot ein. When inserted between amino acids 6 and 7 of the latter, a single -chain antibody fragment (ScFv) specific for human major histocompatib ility complex class I molecules was shown to be able to redefine the t ropism of ecotropic Moloney murine leukemia virus-derived retroviral p articles by allowing infection of major histocompatibility complex cla ss I-positive human cells. At variance with other recently described e xperimental systems, the type of modification adopted here allowed tar geted infection in the absence of coexpressed wild-type env-encoded pr otein molecules. Interestingly, the chimeric ScFv-env protein also ret ained the ability to recognize the ecotropic receptor and allowed infe ction of murine cells, albeit at a reduced efficiency.