Identification of R-peptides in envelope proteins of C-type retroviruses.
Activation of the murine leukaemia virus (MLV) envelope protein (Env) requires proteolytic cleavage of the R-peptide, a 16 amino acid C-terminal part of the cytoplasmic tail (C-tail) of Env. This paper demonstrates the presence of R-peptides in Env proteins of C-type retroviruses of simian, avian and porcine origin. Sequence alignment with the MLV C-tail led to the identification of a conserved hydrophobic protease cleavage motif located in the centre of retroviral Env protein C-tails. Expression of Env proteins, truncated at the predicted cleavage sites, of spleen necrosis virus (SNV), gibbon ape leukaemia virus and porcine endogenous retroviruses resulted in cell-cell fusion as monitored by microscopy and reporter gene fusion assays. Western blot analysis of MLV particles pseudotyped with the SNV Env protein demonstrated proteolytic cleavage of the SNV R-peptide by the MLV protease. Our data suggest that activation of membrane fusion by R-peptide cleavage is a common mode in C-type retroviruses.
Bobkova
Maria
M
Department of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany1.
Stitz
Joern
J
Department of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany1.
Engelstädter
Martin
M
Department of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany1.
Cichutek
Klaus
K
Department of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany1.
Buchholz
Christian J
CJ
Department of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany1.
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004285:Dogs; D010450:Endopeptidases; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D011995:Recombination, Genetic; D012190:Retroviridae / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity*; D012192:Retroviridae Infections / Q000821:virology; D016415:Sequence Alignment; D013155:Spleen Focus-Forming Viruses; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*; D014774:Virulence
D010455:Peptides; D014759:Viral Envelope Proteins; D010450:Endopeptidases