PMID- 20631119 OWN - NLM STAT- MEDLINE DCOM- 20100928 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 84 IP - 19 DP - 2010 Oct TI - Two overlapping domains of a lyssavirus matrix protein that acts on different cell death pathways. PG - 9897-906 LID - 10.1128/JVI.00761-10 [doi] AB - 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. FAU - Larrous, Florence AU - Larrous F AD - Institut Pasteur, Unite Dynamique des lyssavirus et adaptation a l'hote, 75724 Paris Cedex 15, France. FAU - Gholami, Alireza AU - Gholami A FAU - Mouhamad, Shahul AU - Mouhamad S FAU - Estaquier, Jerome AU - Estaquier J FAU - Bourhy, Herve AU - Bourhy H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100714 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (DNA Primers) RN - 0 (DNA, Viral) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 0 (Viral Matrix Proteins) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Amino Acid Sequence MH - Amino Acid Substitution MH - Animals MH - Apoptosis/physiology MH - Base Sequence MH - DNA Primers/genetics MH - DNA, Viral/genetics MH - Dogs MH - Electron Transport Complex IV/antagonists & inhibitors MH - HeLa Cells MH - Host-Pathogen Interactions/physiology MH - Humans MH - Lyssavirus/genetics/pathogenicity/*physiology MH - Models, Molecular MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Peptide Fragments/chemistry/genetics/metabolism MH - Protein Structure, Tertiary MH - Rabies virus/genetics/pathogenicity/physiology MH - Recombinant Proteins/chemistry/genetics/metabolism MH - TNF-Related Apoptosis-Inducing Ligand/physiology MH - Viral Matrix Proteins/*chemistry/genetics/*physiology PMC - PMC2937802 EDAT- 2010/07/16 06:00 MHDA- 2010/09/30 06:00 PMCR- 2011/04/01 CRDT- 2010/07/16 06:00 PHST- 2010/07/16 06:00 [entrez] PHST- 2010/07/16 06:00 [pubmed] PHST- 2010/09/30 06:00 [medline] PHST- 2011/04/01 00:00 [pmc-release] AID - JVI.00761-10 [pii] AID - 0761-10 [pii] AID - 10.1128/JVI.00761-10 [doi] PST - ppublish SO - J Virol. 2010 Oct;84(19):9897-906. doi: 10.1128/JVI.00761-10. Epub 2010 Jul 14.