title: Complementation of a binding-defective retrovirus by a host cell receptor mutant.
abstract: The entry of ecotropic murine leukemia virus (MLV) into cells requires the interaction of the envelope protein (Env) with its receptor, mouse cationic amino acid transporter 1 (mATRC1). An aspartic acid-to-lysine change at position 84 (D84K) of ecotropic Moloney MLV Env abolishes virus binding and infection. We recently identified lysine 234 (rK234) in mATRC1 as a residue that influences virus binding and infection. Here we show that D84K virus infection increased 3,000-fold on cells expressing receptor with an rK234A change and 100,000-fold on cells expressing an rK234D change. The stronger complementation of D84K virus infection by rK234D than by the rK234A receptor suggests that although the major reason for loss of infection of D84K and D84R virus is due to steric hindrance and charge repulsion, the loss of an interaction of D84 with receptor appears to contribute as well. Taken together, these results indicate that D84 is very close to rK234 of mATRC1 in the bound complex and there is likely an interaction between them. The definitive localization of the receptor binding site on SU should facilitate the design of chimeric envelope proteins that target infection to new receptors by replacing the receptor binding site with an exogenous ligand sequence.
authors.affiliation: Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Room G01, Memphis, TN 38163, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qian
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Wang
authors.forename: Cyril
authors.initials: C
authors.lastname: Empig
authors.forename: W French
authors.initials: WF
authors.lastname: Anderson
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Albritton
mesh_terms: D000818:Animals; D015686:Gene Products, env / Q000502:physiology; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D011991:Receptors, Virus / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D015686:Gene Products, env; D011991:Receptors, Virus