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Journal of Virology, January 2005, p. 834-840, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.834-840.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Directed Evolution of Retrovirus Envelope Protein Cytoplasmic Tails Guided by Functional Incorporation into Lentivirus Particles

Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany,¹ Department of Molecular Pharmacology, School of Medicine, Stanford University, Stanford, California,² Molecular Medicine Program, Departments of Immunology and Medicine, Mayo Medical School, Rochester, Minnesota³

Received 3 March 2004/ Accepted 3 September 2004

In contrast to most gammaretrovirus envelope proteins (Env), the Gibbon ape leukemia virus (GaLV) Env protein does not mediate the infectivity of human immunodeficiency virus type 1 (HIV-1) particles. We made use of this observation to set up a directed evolution system by creating a library of GaLV Env variants diversified at three critical amino acids, all located around the R-peptide cleavage site within the cytoplasmic tail. This library was screened for variants that were able to functionally pseudotype HIV-1 vector particles. All selected Env variants mediated the infectivity of HIV-1 vector particles and encoded novel cytoplasmic tail motifs. They were efficiently incorporated into HIV particles, and the R peptide was processed by the HIV protease. Interestingly, in some of the selected variants, the R-peptide cleavage site had shifted closer to the C terminus. These data demonstrate a valuable approach for the engineering of chimeric viruses and vector particles.

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