title: Neuronal retrograde transport of Borna disease virus occurs in signalling endosomes.
abstract: Long-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuroinvasive viruses, such as Borna disease virus (BDV), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. Although BDV is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. In this work, we combined different methodological approaches, such as confocal microscopy and biochemical purification of endosomes, to study BDV retrograde transport. We demonstrate that BDV ribonucleoparticles (composed of the viral genomic RNA, nucleoprotein and phosphoprotein), as well as the matrix protein, are transported towards the nucleus into endocytic carriers. These specialized organelles, called signalling endosomes, are notably used for the retrograde transport of neurotrophins and activated growth factor receptors. Signalling endosomes have a neutral luminal pH and thereby offer protection against degradation during long-range transport. This particularity could allow the viral particles to be delivered intact to the cell body of neurons, avoiding their premature release in the cytoplasm.
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Charlier
authors.affiliation: Molecular Neuropathobiology Laboratory, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Solène
authors.initials: S
authors.lastname: Debaisieux
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Foret
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thouard
authors.affiliation: Molecular Neuropathobiology Laboratory, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez-Dunia
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Cécile E
authors.initials: CE
authors.lastname: Malnou
mesh_terms: D000818:Animals; D001890:Borna Disease / Q000378:metabolism / Q000821:virology*; D001891:Borna disease virus / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D011992:Endosomes / Q000378:metabolism / Q000821:virology*; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D012367:RNA, Viral; D014764:Viral Proteins