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Bornavirus: an equine virus implicated in brain diseases in humans?

Scientists in the Joint Research Unit for Virology* and their partners have offered some answers to this question. For the first time, they have demonstrated that a protein in the Borna virus is able to disturb the formation of neurons in the human brain. Their results support the hypothesis that some neuropsychiatric diseases could be of viral origin.  These findings have been published in PLOS Pathogens.

Human neurons. © INRA, Muriel Coulpier
By Delphine Achour, translated by Vicky Hawken
Updated on 12/06/2016
Published on 11/14/2016

A virus that attacks brain cells in animals

The Borna virus mainly affects horses and sheep. It causes bornavirus disease by attacking the nerve cells of animals and causing encephalitis and/or behavioural disorders which may have a fatal outcome.  In infected horses, mortality rates range from 80% to 100%, while in sheep they exceed 50%.

Bornavirus, a controversial subject

A certain number of epidemiological studies in humans, and experimental studies in animals, have suggested that viruses may cause the malfunction of brain cells without necessarily being fatal to them. It has been suggested that such mechanisms may be responsible for chronic diseases of the central nervous system, and thus be at the origin of certain psychiatric or neurological diseases whose causes are not yet known.

This scenario has notably been suggested for Borna virus. Since the 1980s, different studies performed in humans have indeed suggested that patients with psychiatric diseases had been exposed to this virus. But not all research findings agree on this point. On the contrary, other work has revealed a lack of any evidence for the involvement of the Borna virus in schizophrenic patients.  And to date, no formal proof has been provided of the pathogenic potential of this virus.

To evaluate the risk that this virus might be pathogenic, current research efforts are focusing on understanding how it might disturb brain function in animals or humans. Through which mechanisms might viral cells and molecules intervene?  Scientists in the Joint Research Unit for Virology* and their partners have thus studied the interactions that may develop between the Borna virus and specific cells in the human brain. They chose cells whose malfunction is implicated in numerous psychiatric disorders (depression, psychosis, dementia, etc.).

A virus that can infect human brain cells…

The scientists focused on key cells in the human central nervous system: neural stem cells. Indeed, these cells are the source of two important types of brain cells: neurons and astrocytes.  The scientists thus showed that the Borna virus was able to infect human neural stem cells cultivated in vitro. They also observed that the ability of infected cells to generate neurons was impaired. However, the infection of these stem cells did not hamper the formation of astrocytes.

Human brain cells. Neurons (in red) and astrocytes (in green).. © INRA, INRA, Muriel Coulpier
Human brain cells. Neurons (in red) and astrocytes (in green). © INRA, INRA, Muriel Coulpier


…and a viral protein that alters the formation of specific neurons

The scientists then identified a specific protein in the Borna virus that was able to disturb neurogenesis: phosphoprotein P. They showed in particular that it intervened in the maturation of specific neurons produced by stem cells: GABAergic neurons.

These neurons are specialised in the transmission of a particular chemical messenger: gamma-aminobutyric acid, or GABA. Very widespread in the human central nervous system, this inhibits the activity of neurons and regulates their excitability. If it malfunctions, this could constitute an important factor in the development of certain psychiatric diseases.

Results in favour of the viral origin of certain brain disorders

For the first time, this research team has demonstrated that a viral protein is able to alter the process during which human GABAergic neurons are formed.  These findings support the hypothesis that viruses may be involved in the development of psychiatric diseases. They underline the usefulness of pursuing efforts along this research path, as they could ultimately lead to the development of new therapeutic approaches in human neuropsychiatric medicine.

* Joint Research Unit for Virology ( INRA/ANSES/ENVA)

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