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Article Dans Une Revue FASEB Journal Année : 2016

Manipulation of the N-terminal sequence of the Borna disease virus X protein improves its mitochondrial targeting and neuroprotective potential

Cecile A. Ferre
  • Fonction : Auteur
Noelie Davezac
  • Fonction : Auteur
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Anne Thouard
  • Fonction : Auteur
Pascale Belenguer
Marie-Christine Miquel
Daniel Gonzalez-Dunia
Marion Szelechowski
  • Fonction : Auteur

Résumé

To favor their replication, viruses express proteins that target diverse mammalian cellular pathways. Due to the limited size of many viral genomes, such proteins are endowed with multiple functions, which require targeting to different subcellular compartments. One salient example is the X protein of Borna disease virus, which is expressed both at the mitochondria and in the nucleus. Moreover, we recently demonstrated that mitochondrial X protein is neuroprotective. In this study, we sought to examine the mechanisms whereby the X protein transits between subcellular compartments and to define its localization signals, to enhance its mitochondrial accumulation and thus, potentially, its neuroprotective activity. We transfected plasmids expressing fusion proteins bearing different domains of X fused to enhanced green fluorescent protein (eGFP) and compared their subcellular localization to that of eGFP. We observed that the 5-16 domain of X was responsible for both nuclear export and mitochondrial targeting and identified critical residues for mitochondrial localization. We next took advantage of these findings and constructed mutant X proteins that were targeted only to the mitochondria. Such mutants exhibited enhanced neuroprotective properties in compartmented cultures of neurons grown in microfluidic chambers, thereby confirming the parallel between mitochondrial accumulation of the X protein and its neuroprotective potential.-Ferre C. A., Davezac, N., Thouard, A., Peyrin, J. M., Belenguer, P., Miquel, M.-C., Gonzalez-Dunia, D., Szelechowski, M. Manipulation of the N-terminal sequence of the Borna disease virus X protein improves its mitochondrial targeting and neuroprotective potential. FASEB J. 30, 1523-1533 (2016). www.fasebj.org
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Dates et versions

hal-01542857 , version 1 (20-06-2017)

Identifiants

Citer

Cecile A. Ferre, Noelie Davezac, Anne Thouard, Jean-Michel Peyrin, Pascale Belenguer, et al.. Manipulation of the N-terminal sequence of the Borna disease virus X protein improves its mitochondrial targeting and neuroprotective potential. FASEB Journal, 2016, 30 (4), pp.1523-1533. ⟨10.1096/fj.15-279620⟩. ⟨hal-01542857⟩
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