Sequences in the Cytoplasmic Tail of the Gibbon Ape Leukemia Virus Envelope Protein That Prevent Its Incorporation into Lentivirus Vectors

• DOI: 10.1128/jvi.75.9.4129-4138.2001
• Publication Date: 2002-07-27T09:55:53Z
• Authors: Ilias Christodoul...; Paula M. Cannon
• Keywords: Ectodomain

ABSTRACT Pseudotyping retrovirus and lentivirus vectors with different viral fusion proteins is a useful strategy to alter the host range of vectors. Although are efficiently pseudotyped by Env from several subtypes murine leukemia virus (MuLV), related protein gibbon ape (GaLV) does not form functional pseudotypes. We have determined that this arises because an inability GaLV be incorporated into vector particles. By exploiting homology between MuLV proteins, we mapped determinants incompatibility in Env. Three modifications allowed pseudotype human immunodeficiency type 1 particles were identified: removal R peptide (C-terminal half cytoplasmic domain), replacement whole tail corresponding region, mutation two residues upstream cleavage site. In addition, previously proposed enhances their fusogenicity transmitting conformational change ectodomain (Y. Zhao et al., J. Virol. 72:5392–5398, 1998). Our analysis chimeric MuLV/GaLV provides further evidence support model suggests proper function involves both interactions within more long-range tail, membrane-spanning protein.