Modular organization of the Friend murine leukemia virus envelope protein underlies the mechanism of infection

Retrovirus infection is initiated by receptor-dependent fusion of the envel ope to the cell membrane. The modular organization of the envelope protein of C type retroviruses has been exploited to investigate how binding of the surface subunit (SU) to receptor triggers fusion mediated by the transmemb rane (TM) subunit, We show that deletion of the receptor-binding domain (RB D) from SU of Friend murine leukemia virus (Fr-MLV) abolishes infection tha t is restored by supplying RED as a soluble protein, Infection by this mech anism remains dependent on receptor expression. When membrane attachment of the virus lacking RED is reestablished by inserting the hormone erythropoi etin, infection remains dependent on the RBD/receptor complex. However, inf ection increases 50-fold to 5 x 10(5) units/ml on cells that also express t he erythropoietin receptor. Soluble RED from Fr-MLV also restores infection by amphotropic and xenotropic MLVs in which RBD is deleted. These experime nts demonstrate that RED has two functions: mediating virus attachment and activating the fusion mechanism. In addition, they indicate that receptor e ngagement triggers fusion by promoting a subgroup-independent functional in teraction between RED and the remainder of SU and/or TM.