Mechanism of the Antiviral Action of 1-β-
            <scp>d</scp>
            -Arabinofuranosylcytosine on Borna Disease Virus

Volmer, Romain; Bajramović, Jeffrey J.; Schneider, Urs; Ufano, Sandra; Pochet, Sylvie; Gonzalez–Dunia, Daniel

doi:10.1128/jvi.79.7.4514-4518.2005

Cited by 7 publications

(2 citation statements)

References 30 publications

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“…As BDV is able to infect a wide variety of cell types in vitro, even those of nonneuronal origin, we next asked whether this histone acetylation decrease was also observed in other cell types. To this end, histone acetylation levels were evaluated in Vero cells persistently infected by BDV (Vero-BV [24]). We observed that histone acetylation levels were also decreased in Vero-BV cells and that, remarkably, the histone acetylation occurred on exactly the same lysine residues as in the primary neuronal cultures (Fig.…”

Section: Resultsmentioning

confidence: 99%

Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication

Bonnaud

Szelechowski

Bétourné

et al. 2015

J Virol

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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. This has led to our hypothesis that such an interaction may trigger epigenetic changes in the host cell. Here, we focused on histone acetylation, which plays key roles in epigenetic regulation of gene expression, notably for neurons. We performed a comparative analysis of histone acetylation patterns of neurons infected or not infected by BDV, which revealed that infection decreases histone acetylation on selected lysine residues. We showed that the BDV phosphoprotein (P) is responsible for these perturbations, even when it is expressed alone independently of the viral context, and that this action depends on its phosphorylation by protein kinase C. We also demonstrated that BDV P inhibits cellular histone acetyltransferase activities. Finally, by pharmacologically manipulating cellular acetylation levels, we observed that inhibiting cellular acetyl transferases reduces viral replication in cell culture. Our findings reveal that manipulation of cellular epigenetics by BDV could be a means to modulate viral replication and thus illustrate a fascinating example of virus-host cell interaction. IMPORTANCEPersistent DNA viruses often subvert the mechanisms that regulate cellular chromatin dynamics, thereby benefitting from the resulting epigenetic changes to create a favorable milieu for their latent and persistent states. Here, we reasoned that Borna disease virus (BDV), the only RNA virus known to durably persist in the nucleus of infected cells, notably neurons, might employ a similar mechanism. In this study, we uncovered a novel modality of virus-cell interaction in which BDV phosphoprotein inhibits cellular histone acetylation by interfering with histone acetyltransferase activities. Manipulation of cellular histone acetylation is accompanied by a modulation of viral replication, revealing a perfect adaptation of this "ancient" virus to its host that may favor neuronal persistence and limit cellular damage.

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Section: Resultsmentioning

confidence: 99%

Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication

Bonnaud

Szelechowski

Bétourné

et al. 2015

J Virol

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“…However, its use is compromised by side effects. Some other antivirals have also been developed against BDV, but these trials have so far remained in the initial phase (Planz et al, 2001;Bajramovic et al, 2004;Volmer et al, 2005;Qian et al, 2010).…”

Section: Treatment and Prevention Of Bdmentioning

confidence: 99%

Epidemiology and host spectrum of Borna disease virus infections

Kinnunen

Palva

Vaheri

et al. 2013

Journal of General Virology

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Borna disease virus (BDV) has gained lot of interest because of its zoonotic potential, ability to introduce cDNA of its RNA transcripts into host genomes, and ability to cause severe neurobehavioural diseases. Classical Borna disease is a progressive meningoencephalomyelitis in horses and sheep, known in central Europe for centuries. According to current knowledge, BDV or a close relative also infects several other species, including humans at least occasionally, in central Europe and elsewhere, but the existence of potential ‘human Borna disease’ with its suspected neuropsychiatric symptoms is highly controversial. The recent detection of endogenized BDV-like genes in primate and various other vertebrate genomes confirms that at least ancient bornaviruses did infect our ancestors. The epidemiology of BDV is largely unknown, but accumulating evidence indicates vectors and reservoirs among small wild mammals. The aim of this review is to bring together the current knowledge on epidemiology of BDV infections. Specifically, geographical and host distribution are addressed and assessed in the critical light of the detection methods used. We also review some salient clinical aspects.

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Ribavirin inhibits Borna disease virus proliferation and fatal neurological diseases in neonatally infected gerbils

Lee¹,

Matsunaga²,

Ikuta³

et al. 2008

Antiviral Research

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Mechanism of the Antiviral Action of 1-β- d -Arabinofuranosylcytosine on Borna Disease Virus

Cited by 7 publications

References 30 publications

Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication

Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication

Epidemiology and host spectrum of Borna disease virus infections

Ribavirin inhibits Borna disease virus proliferation and fatal neurological diseases in neonatally infected gerbils

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