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Suppression of feline coronavirus replication in vitro by cyclosporin A.

Tanaka Y, Sato Y, Osawa S, Inoue M, Tanaka S, Sasaki T - Vet. Res. (2012)

Bottom Line: Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells.Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway.In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan. ytanaka@nvlu.ac.jp.

ABSTRACT
The feline infectious peritonitis virus (FIPV) is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP) but not CyP) did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.

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Cyclosporin A inhibits cytopathic effects of FIPV on fcwf-4 cells. (A) WST-8 assay of fcwf-4 cells cultured with indicated concentrations of CsA. Error bars indicate means ± 2SD. *P, **P < 0.05. (B) Plaques counted in FIPV-infected fcwf-4 cells incubated with or without CsA. Cells infected with FIPV were incubated with various concentrations of CsA.
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Figure 1: Cyclosporin A inhibits cytopathic effects of FIPV on fcwf-4 cells. (A) WST-8 assay of fcwf-4 cells cultured with indicated concentrations of CsA. Error bars indicate means ± 2SD. *P, **P < 0.05. (B) Plaques counted in FIPV-infected fcwf-4 cells incubated with or without CsA. Cells infected with FIPV were incubated with various concentrations of CsA.

Mentions: We initially assessed the effects of CsA on FIPV RNA replication using cytotoxicity assays. Cyclosporin A at concentrations of 0–6.3 μM (cytotoxic dose50, 14.1 ± 1.72 μM) did not affect fcwf-4 cell viability (Figure 1A) and dose-dependently reduced the numbers of FIPV plaques (Figure 1B), whereas 10 μM CsA was slightly cytotoxic. Cyclosporin A blocks both the enzymatic activities of CyP that lead to the calcineurin (CN)-NF-AT and the P-glycoprotein pathway. We therefore assessed the effect of various concentrations of FK506, which also blocks the NF-AT pathway, on cell viability to confirm that CsA inhibited FIPV through this pathway. The cytopathic inhibitory effects did not significantly differ in the presence or absence of 0.08 - 10 μM FK506 (Figure 2B) and cell viability was not affected by 10 μM FK506 (Figure 2A).


Suppression of feline coronavirus replication in vitro by cyclosporin A.

Tanaka Y, Sato Y, Osawa S, Inoue M, Tanaka S, Sasaki T - Vet. Res. (2012)

Cyclosporin A inhibits cytopathic effects of FIPV on fcwf-4 cells. (A) WST-8 assay of fcwf-4 cells cultured with indicated concentrations of CsA. Error bars indicate means ± 2SD. *P, **P < 0.05. (B) Plaques counted in FIPV-infected fcwf-4 cells incubated with or without CsA. Cells infected with FIPV were incubated with various concentrations of CsA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403912&req=5

Figure 1: Cyclosporin A inhibits cytopathic effects of FIPV on fcwf-4 cells. (A) WST-8 assay of fcwf-4 cells cultured with indicated concentrations of CsA. Error bars indicate means ± 2SD. *P, **P < 0.05. (B) Plaques counted in FIPV-infected fcwf-4 cells incubated with or without CsA. Cells infected with FIPV were incubated with various concentrations of CsA.
Mentions: We initially assessed the effects of CsA on FIPV RNA replication using cytotoxicity assays. Cyclosporin A at concentrations of 0–6.3 μM (cytotoxic dose50, 14.1 ± 1.72 μM) did not affect fcwf-4 cell viability (Figure 1A) and dose-dependently reduced the numbers of FIPV plaques (Figure 1B), whereas 10 μM CsA was slightly cytotoxic. Cyclosporin A blocks both the enzymatic activities of CyP that lead to the calcineurin (CN)-NF-AT and the P-glycoprotein pathway. We therefore assessed the effect of various concentrations of FK506, which also blocks the NF-AT pathway, on cell viability to confirm that CsA inhibited FIPV through this pathway. The cytopathic inhibitory effects did not significantly differ in the presence or absence of 0.08 - 10 μM FK506 (Figure 2B) and cell viability was not affected by 10 μM FK506 (Figure 2A).

Bottom Line: Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells.Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway.In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo, 180-8602, Japan. ytanaka@nvlu.ac.jp.

ABSTRACT
The feline infectious peritonitis virus (FIPV) is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP) but not CyP) did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.

Show MeSH
Related in: MedlinePlus