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Journal articles
Two overlapping domains of a lyssavirus matrix protein that acts on different cell death pathways.
Abstract : The lyssavirus matrix (M) protein induces apoptosis. The regions of the M protein that are essential for triggering cell death pathways are not yet clearly defined. We therefore compared the M proteins from two viruses that have contrasting characteristics in terms of cellular apoptosis: a genotype 3 lyssavirus, Mokola virus (MOK), and a genotype 1 rabies virus isolated from a dog from Thailand (THA). We identified a 20-amino-acid fragment (corresponding to positions 67 to 86) that retained the cell death activities of the full-length M protein from MOK via both the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and inhibition of cytochrome c oxidase (CcO) activity. We found that the amino acids at positions 77 and 81 have an essential role in triggering these two cell death pathways. Directed mutagenesis demonstrated that the amino acid at position 77 affects CcO activity, whereas the amino acid at position 81 affects TRAIL-dependent apoptosis. Mutations in the full-length M protein that compromised induction of either of these two pathways resulted in delayed apoptosis compared with the time to apoptosis for the nonmutated control.
Keywords :
Mutagenesis
Molecular
Molecular Sequence Data
Amino Acid Sequence
Amino Acid Substitution
Animals
Apoptosis
Base Sequence
DNA Primers
DNA
Viral
Dogs
Electron Transport Complex IV
HeLa Cells
Host-Pathogen Interactions
Humans
Lyssavirus
Models
Site-Directed
Peptide Fragments
Protein Structure
Tertiary
Rabies virus
Recombinant Proteins
TNF-Related Apoptosis-Inducing Ligand
Viral Matrix Proteins
https://hal-pasteur.archives-ouvertes.fr/pasteur-01491943
Contributor : Anne Lassailly-Bondaz <>
Submitted on : Friday, March 17, 2017 - 4:27:01 PM
Last modification on : Tuesday, June 16, 2020 - 3:34:02 PM
Long-term archiving on: : Sunday, June 18, 2017 - 1:31:14 PM
Contributor : Anne Lassailly-Bondaz <>
Submitted on : Friday, March 17, 2017 - 4:27:01 PM
Last modification on : Tuesday, June 16, 2020 - 3:34:02 PM
Long-term archiving on: : Sunday, June 18, 2017 - 1:31:14 PM
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J. Virol.-2010-Larrous-9897-90...
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