Inhibition of murine leukemia virus envelope protein (env) processing by intracellular expression of the env N-terminal heptad repeat region.
A conserved structural motif in the envelope proteins of several viruses consists of an N-terminal, alpha-helical, trimerization domain and a C-terminal region that refolds during fusion to bind the N-helix trimer. Interaction between the N and C regions is believed to pull viral and target membranes together in a crucial step during membrane fusion. For several viruses with type I fusion proteins, C regions pack as alpha-helices in the grooves between N-helix monomers, and exogenously added N- and C-region peptides block fusion by inhibiting the formation of the six-helix bundle. For other viruses, including influenza virus and murine leukemia virus (MLV), there is no evidence for comparably extended C-region alpha-helices, although a short, non-alpha-helical interaction structure has been reported for influenza virus. We tested candidate N-helix and C-region peptides from MLV for their ability to inhibit cell fusion but found no inhibitory activity. In contrast, intracellular expression of the MLV N-helix inhibited fusion by efficiently blocking proteolytic processing and intracellular transport of the envelope protein. The results highlight another mechanism by which the N-helix peptides can inhibit fusion.
Ou
Wu
W
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 336, Bethesda, MD 20892, USA.
Silver
Jonathan
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020449:Repetitive Sequences, Amino Acid; D014162:Transfection
D017931:DNA Primers; D015686:Gene Products, env; D010446:Peptide Fragments