Functional interactions between monomers of the retroviral envelope protein complex.

Retroviral vectors have been widely used in human gene therapy protocols. Entry into target cells is directed by the retroviral envelope protein, with receptor binding and postbinding fusion functions contributed mainly by the SU and TM subunits, respectively. We have generated mutants of the Moloney murine leukemia virus (MoMuLV) envelope protein with mutations in both the receptor binding domain of SU and throughout the TM subunit that are functionally inactive when expressed individually. However, the coexpression of these two classes of mutants partially restores envelope protein function and allows transduction. Several lines of evidence indicate that this complementation occurs in trans within envelope protein heterooligomers. The finding that the binding and postbinding functions of a retroviral envelope protein can be contributed by two different monomers should assist in the engineering of envelope proteins for tissue-specific gene delivery.