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Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

Musser JM, Heatley JJ, Koinis AV, Suchodolski PF, Guo J, Escandon P, Tizard IR - PLoS ONE (2015)

Bottom Line: We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells.The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition.This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

View Article: PubMed Central - PubMed

Affiliation: Schubot Exotic Bird Health Center, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America; Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

No MeSH data available.


Related in: MedlinePlus

Guanosine inhibition of ribavirin antiviral activity on PaBV-4.(A) qRT-PCR results reported as mean (±SD) relative change in P gene mRNA expression, compared to control group (neither guanosine nor ribavirin added). *, compared with no guanosine within ribavirin treatment group (P <0.05, ANOVA with Holm-Sidak method). (B) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles positive stained cell foci. (C) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles of the percentage area of infected cells.
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pone.0134080.g006: Guanosine inhibition of ribavirin antiviral activity on PaBV-4.(A) qRT-PCR results reported as mean (±SD) relative change in P gene mRNA expression, compared to control group (neither guanosine nor ribavirin added). *, compared with no guanosine within ribavirin treatment group (P <0.05, ANOVA with Holm-Sidak method). (B) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles positive stained cell foci. (C) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles of the percentage area of infected cells.

Mentions: To test whether depletion of GTP pools was a mechanism of action contributing to the antiviral activity of ribavirin, 3 to 28 μg/mL guanosine was added to infected cells treated with ribavirin. The addition of guanosine reduced the antiviral activity of ribavirin in a dose-dependent manner. The relative expression of the P gene mRNA was significantly (P≤ 0.05) increased, between 3 to 5 fold increase, with the addition of 14 and 28 μg/mL of guanosine when compared to when ribavirin was present without guanosine (Fig 6A).


Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

Musser JM, Heatley JJ, Koinis AV, Suchodolski PF, Guo J, Escandon P, Tizard IR - PLoS ONE (2015)

Guanosine inhibition of ribavirin antiviral activity on PaBV-4.(A) qRT-PCR results reported as mean (±SD) relative change in P gene mRNA expression, compared to control group (neither guanosine nor ribavirin added). *, compared with no guanosine within ribavirin treatment group (P <0.05, ANOVA with Holm-Sidak method). (B) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles positive stained cell foci. (C) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles of the percentage area of infected cells.
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getmorefigures.php?uid=PMC4519282&req=5

pone.0134080.g006: Guanosine inhibition of ribavirin antiviral activity on PaBV-4.(A) qRT-PCR results reported as mean (±SD) relative change in P gene mRNA expression, compared to control group (neither guanosine nor ribavirin added). *, compared with no guanosine within ribavirin treatment group (P <0.05, ANOVA with Holm-Sidak method). (B) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles positive stained cell foci. (C) Indirect immunocytochemistry results presented as median ± 25th and 75th percentiles of the percentage area of infected cells.
Mentions: To test whether depletion of GTP pools was a mechanism of action contributing to the antiviral activity of ribavirin, 3 to 28 μg/mL guanosine was added to infected cells treated with ribavirin. The addition of guanosine reduced the antiviral activity of ribavirin in a dose-dependent manner. The relative expression of the P gene mRNA was significantly (P≤ 0.05) increased, between 3 to 5 fold increase, with the addition of 14 and 28 μg/mL of guanosine when compared to when ribavirin was present without guanosine (Fig 6A).

Bottom Line: We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells.The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition.This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

View Article: PubMed Central - PubMed

Affiliation: Schubot Exotic Bird Health Center, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America; Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

No MeSH data available.


Related in: MedlinePlus