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Induction of resistance to herpesvirus and calicivirus in the domestic cat by stimulation of the innate immune system


Rüegger, V L. Induction of resistance to herpesvirus and calicivirus in the domestic cat by stimulation of the innate immune system. 2011, University of Zurich, Vetsuisse Faculty.

Abstract

CpG VR-1, a type A CpG ODN and TLR9 ligand, has been shown to induce effective production of type I IFN in mice. In this study, the potential of this molecule to stimulate the feline innate immune system and temporarily induce unspecific resistance to viral infections in vitro was tested. In feline PBMCs, CpG VR-1 was able to highly up-regulate the gene expression of type I IFNs (IFN?, IFN?, IFN? by mean factors of 1440, 394 and 1908, respectively) and Mx (49x), to induce the proinflammatory cytokines IL-6 (10x) and TNF? (2x) and enhance the expression of IL-12 (7.5x) and IL-15 (7.4x) as well as Granzyme B (2.5x). Also, stimulated PBMCs released soluble factors into the cell culture supernatant, among which biologically active type I IFNs. When CRFK and Fcwf-4 cells were incubated with these supernatants, not only Mx gene expression was highly induced but replication of FCV, FHV and VSV could also be inhibited in these cells. The expression factors of the Mx gene in the target cells correlated directly with those of the type I IFNs in the PBMCs. The survival of the Fcwf-4 cells upon viral challenge (FCV, FHV, or VSV) was correlated to their Mx gene expression induced by the treatment with the same supernatants. In CRFK cells, only the inhibition of VSV was correlated to the Mx gene expression. The potent inhibition of viral replication upon target cell treatment with the supernatants from PBMCs treated with CpG VR-1 represents promising results for further in vivo studies.

CpG VR-1, a type A CpG ODN and TLR9 ligand, has been shown to induce effective production of type I IFN in mice. In this study, the potential of this molecule to stimulate the feline innate immune system and temporarily induce unspecific resistance to viral infections in vitro was tested. In feline PBMCs, CpG VR-1 was able to highly up-regulate the gene expression of type I IFNs (IFN?, IFN?, IFN? by mean factors of 1440, 394 and 1908, respectively) and Mx (49x), to induce the proinflammatory cytokines IL-6 (10x) and TNF? (2x) and enhance the expression of IL-12 (7.5x) and IL-15 (7.4x) as well as Granzyme B (2.5x). Also, stimulated PBMCs released soluble factors into the cell culture supernatant, among which biologically active type I IFNs. When CRFK and Fcwf-4 cells were incubated with these supernatants, not only Mx gene expression was highly induced but replication of FCV, FHV and VSV could also be inhibited in these cells. The expression factors of the Mx gene in the target cells correlated directly with those of the type I IFNs in the PBMCs. The survival of the Fcwf-4 cells upon viral challenge (FCV, FHV, or VSV) was correlated to their Mx gene expression induced by the treatment with the same supernatants. In CRFK cells, only the inhibition of VSV was correlated to the Mx gene expression. The potent inhibition of viral replication upon target cell treatment with the supernatants from PBMCs treated with CpG VR-1 represents promising results for further in vivo studies.

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Additional indexing

Item Type:Dissertation
Referees:Lutz H, Ackermann M
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Language:English
Date:2011
Deposited On:15 Mar 2012 21:49
Last Modified:05 Apr 2016 15:39
Number of Pages:86
Related URLs:http://opac.nebis.ch/F/?local_base=NEBIS&CON_LNG=GER&func=find-b&find_code=SYS&request=006527939
Permanent URL: https://doi.org/10.5167/uzh-59804

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