Characterization of R peptide of murine leukemia virus envelope glycoproteins in syncytium formation and entry.
The C-terminal R peptide of ecotropic murine leukemia virus (MLV) envelope protein (Env) negatively controls membrane fusion activity. The R peptide cleavage during virion maturation activates its fusogenicity and is required for viral entry. We analyzed fusogenicity and transduction efficiency of mutant Env proteins of ecotropic, amphotropic, polytropic, and xenotropic MLVs. As the result, we found that the hydrophobic amino acid residues around the R peptide cleavage site are important for membrane fusion inhibition by the R peptide. In addition, we found that Env complexes with R peptide-truncated and -containing Env proteins have lower fusogenicity and transduction efficiency than those with the R-peptide-truncated Env alone, suggesting that efficient R peptide cleavage is required for efficient MLV vector transduction. The role of R peptide cleavage in amphotropic, polytropic, and xenotropic MLV infection has not been investigated. We found in this study that the R peptide cleavage is required for amphotropic, xenotropic, and polytropic MLV vector transduction, like with ecotropic MLV. The R-peptide-truncated Env proteins of the xenotropic and polytropic MLVs, however, had much lower fusogenicity than those of the ecotropic and amphotropic MLVs. These results provide valuable information for construction of efficient MLV vectors and for understanding the retroviral entry mechanism.
Kubo
Y
Y
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. yoshinao@net.nagasaki-u.ac.jp
Tominaga
C
C
Yoshii
H
H
Kamiyama
H
H
Mitani
C
C
Amanuma
H
H
Yamamoto
N
N
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005822:Genetic Vectors; D015726:Giant Cells / Q000378:metabolism*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008561:Membrane Fusion; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000378:metabolism / Q000472:pathogenicity*; D009154:Mutation; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D009842:Oligopeptides; C080708:R peptide; D014759:Viral Envelope Proteins