Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity.

Borna disease viruses (BoDV) have recently emerged as zoonotic neurotropic pathogens. These persistent RNA viruses assemble nuclear replication centers (vSPOT) in close interaction with the host chromatin. However, the topology of this interaction and its consequences on neuronal function remain unexplored.

HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons.

Mortalin is a mitochondrial chaperone protein involved in quality control of proteins imported into the mitochondrial matrix, which was recently described as a sensor of neuronal stress. Mortalin is down-regulated in neurons of patients with neurodegenerative diseases and levels of Mortalin expression are correlated with neuronal fate in animal models of Alzheimer's disease or cerebral ischemia. To date, however, the links between Mortalin levels, its impact on mitochondrial function and morphology and, ultimately, the initiation of neurodegeneration, are still unclear.

Hippocampal expression of a virus-derived protein impairs memory in mice.

The analysis of the biology of neurotropic viruses, notably of their interference with cellular signaling, provides a useful tool to get further insight into the role of specific pathways in the control of behavioral functions. Here, we exploited the natural property of a viral protein identified as a major effector of behavioral disorders during infection. We used the phosphoprotein (P) of Borna disease virus, which acts as a decoy substrate for protein kinase C (PKC) when expressed in neurons and disrupts synaptic plasticity.

Effect of tryptase inhibition on joint inflammation: a pharmacological and lentivirus-mediated gene transfer study.

Background: Increasing evidences indicate that an unbalance between tryptases and their endogenous inhibitors, leading to an increased proteolytic activity, is implicated in the pathophysiology of rheumatoid arthritis. The aim of the present study was to evaluate the impact of tryptase inhibition on experimental arthritis.

Methods: Analysis of gene expression and regulation in the mouse knee joint was performed by RT-qPCR and in situ hybridization.

Neuronal retrograde transport of Borna disease virus occurs in signalling endosomes.

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.

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

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.

Borna disease virus phosphoprotein modulates epigenetic signaling in neurons to control viral replication.

Unlabelled: Understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. Borna disease virus (BDV) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. It is now established that BDV ensures its long-term maintenance in infected cells through a stable interaction of viral components with the host cell chromatin, in particular, with core histones.

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease.

Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death.

Conserved aromatic residues of the hepatitis B virus Precore propeptide are involved in a switch between distinct dimeric conformations and essential in the formation of heterocapsids.

The Hepatitis B virus Precore protein, present in the secretory pathway as the HBeAg precursor, can associate in the cytoplasm with the Core protein to form heterocapsids, likely to favor viral persistence. Core and Precore proteins share their primary sequence except for ten additional aminoacids at the N-terminus of Precore. To address the role of this propeptide sequence in the formation of Precore heterocapsids, we designed a Precore mutant in which the two propeptide tryptophans are replaced by glycines.

Ribosome can resume the translation in both +1 or -1 frames after encountering an AGA cluster in Escherichia coli.

In Escherichia coli the rare codons AGG, AGA and CGA are reported to have a detrimental effect on protein synthesis, especially during the expression of heterologous proteins. In the present work, we have studied the impact of successive clusters of these rare codons on the accuracy of mRNA translation in E. coli.