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

Lee, Byeong-Jae; Matsunaga, Hidenori; Ikuta, Kazuyoshi; Tomonaga, Keizō

doi:10.1016/j.antiviral.2008.08.001

Cited by 12 publications

(12 citation statements)

References 29 publications

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“…Our results confirmed that, like the mammalian bornavirus BoDV-1 (Jordan et al, 1999;Lee et al, 2008;Mizutani et al, 1998Mizutani et al, , 1999, parrot bornaviruses are susceptible to ribavirin treatment in cell culture. Interestingly, we found that continuous ribavirin treatment of infected avian QM7 cell cultures resulted in a marked decrease of viral RNA levels and bornavirus-positive cells as assessed by indirect immunofluorescence, but complete virus elimination was not achieved, even when ribavirin was combined with IFNa.…”

supporting

confidence: 79%

“…The nucleoside analogue ribavirin is active against a broad range of RNA viruses (Day et al, 2005;Graci et al, 2007;Gu et al, 2006;Leyssen et al, 2005;Moreno et al, 2011;Pauly & Lauring, 2015;Severson et al, 2003), including the mammalian Borna disease virus 1 (BoDV-1), which is a close relative of the avian bornaviruses (Kuhn et al, 2015). Several studies demonstrated that ribavirin can inhibit BoDV-1 in mammalian cell lines (Jordan et al, 1999;Mizutani et al, 1998Mizutani et al, , 1999 as well as in experimentally infected gerbils (Lee et al, 2008). More recently, a similar antiviral effect was described also for duck embryo fibroblast (DEF) cultures freshly infected with PaBV-4 (Musser et al, 2015).…”

mentioning

confidence: 99%

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Synergistic antiviral activity of ribavirin and interferon-α against parrot bornaviruses in avian cells

Reuter

Horie

Höper

et al. 2016

Journal of General Virology

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Avian bornaviruses are the causative agents of proventricular dilatation disease (PDD), a widely distributed and often fatal disease in captive psittacines. Because neither specific prevention measures nor therapies against PDD and bornavirus infections are currently available, new antiviral strategies are required to improve animal health. We show here that the nucleoside analogue ribavirin inhibited bornavirus activity in a polymerase reconstitution assay and reduced viral load in avian cell lines infected with two different parrot bornaviruses. Furthermore, we observed that ribavirin enhanced type I IFN signalling in avian cells. Combined treatment of avian bornavirus-infected cells with ribavirin and recombinant IFN-a strongly enhanced the antiviral efficiency compared to either drug alone. The combined use of ribavirin and type I IFN might represent a promising new strategy for therapeutic treatment of captive parrots persistently infected with avian bornaviruses.

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supporting

confidence: 79%

mentioning

confidence: 99%

Synergistic antiviral activity of ribavirin and interferon-α against parrot bornaviruses in avian cells

Reuter

Horie

Höper

et al. 2016

Journal of General Virology

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“…Intracerebrally administered ribavirin interferes with BDV replication and results in clinical improvement, although not in viral clearance in rodents (Jordan et al, 1999;Solbrig et al, 2002;Lee et al, 2008). However, its use is compromised by side effects.…”

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 has been reported to suppress bornavirus both in in vitro (10) and in vivo (11,12) conditions. Partial and complete suppression of bornavirus can be obtained with ribavirin at a concentration of 1 μg/mL and 10 μg/mL, respectively (10) In both cases, symptoms improved 2 weeks after the initiation of ribavirin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Ribavirin-a broad spectrum anti-viral agent-has been reported to suppress bornavirus infections both in in vitro (10) and in vivo (11,12) conditions. We therefore previously performed a clinical trial of oral ribavirin administration in nine patients, and reported significant improvement in two of the patients (13,14).…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Two Neuropsychiatric Cases Seropositive for Bornavirus Improved by Ribavirin

et al. 2018

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A c c e p t e d M a n u s c r i p t While we had previously detected anti-bornavirus antibodies via radioligand assay in psychiatric patients, we had not examined the viral pathogenicity in these individuals.Herein, we present two psychiatric patients who were seropositive for bornavirus and whose treatment-resistant symptoms improved by oral administration of ribavirin, a broad-spectrum antiviral agent. Cerebrospinal fluid analysis indicated that the ribavirin affected the central nervous system of these patients. Ribavirin ameliorated intermittent involuntary head shaking, which is reminiscent of a symptom observed in bornavirus-infected animals. Using radioligand assays to examine the serial sera of these patients, we found a relationship between the titers of anti-bornavirus antibodies and the change in the patients' symptoms. Our findings suggest there is a relationship between bornavirus and human symptoms and that ribavirin may be useful in suppressing chronic bornavirus infection in some neuropsychiatric patients. However, the possibility remains that some other known or unknown virus other than bornavirus, which is sensitive to ribavirin, may have caused the symptoms. Additional evidence that directly indicates the causative relationship between bornavirus and human symptoms is needed before establishing the pathogenesis and treatment for human bornavirus infection. .

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

Cited by 12 publications

References 29 publications

Synergistic antiviral activity of ribavirin and interferon-α against parrot bornaviruses in avian cells

Synergistic antiviral activity of ribavirin and interferon-α against parrot bornaviruses in avian cells

Epidemiology and host spectrum of Borna disease virus infections

Two Neuropsychiatric Cases Seropositive for Bornavirus Improved by Ribavirin

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