Matrix protein of Vesicular stomatitis virus harbours a cryptic mitochondrial-targeting motif.
Vesicular stomatitis virus (VSV) is a rhabdovirus that has attracted attention of late as an oncolytic virus and as a vaccine vector. Mutations in the matrix (M) gene of VSV yield attenuated strains that may be very useful in both settings. As a result of this interest in the M protein, this study analysed various M-green fluorescent protein (GFP) fusion constructs. Remarkably, fusion of the N terminus of the M protein to GFP targeted the fluorescent protein to the surface of mitochondria. Mutational analysis indicated that a mitochondrial-targeting motif exists within aa 33-67. Expression of these fusion proteins led to loss of mitochondrial membrane permeability and to an alteration in mitochondrial organization mirroring that seen during viral infection. In addition, a portion of the M protein present in infected cells co-purified with mitochondria. This work may indicate a novel function for this multifunctional viral protein.
Lichty
Brian D
BD
Centre for Gene Therapeutics, McMaster University, 1200 Main Street W MDCL-5023, Hamilton, ON L8N 3Z5, Canada.
McBride
Heidi
H
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada.
Hanson
Stephen
S
Centre for Gene Therapeutics, McMaster University, 1200 Main Street W MDCL-5023, Hamilton, ON L8N 3Z5, Canada.
Bell
John C
JC
Ottawa Regional Cancer Centre, University of Ottawa, 503 Smyth Road, Ottawa, ON, Canada.
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D010539:Permeability; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C094460:M protein, Vesicular stomatitis virus; D014763:Viral Matrix Proteins