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Journal of Virology, June 2004, p. 5766-5772, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5766-5772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Complementation of a Binding-Defective Retrovirus by a Host Cell Receptor Mutant

Zhaohui Qian,1 Hongzhe Wang,1 Cyril Empig,2,{dagger} W. French Anderson,2 and Lorraine M. Albritton1*

Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163,1 Gene Therapy Laboratories, Norris Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 900332

Received 8 May 2003/ Accepted 19 February 2004

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.


* Corresponding author. Mailing address: Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Room G01, Memphis, TN 38163. Phone: (901) 448-5521. Fax: (901) 448-7360. E-mail: lalbritton{at}utmem.edu.

{dagger} Present address: VaxGen, South San Francisco, CA 94080.


Journal of Virology, June 2004, p. 5766-5772, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5766-5772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.