Stimulation with a class A CpG oligonucleotide enhances resistance to infection with feline viruses from five different families

Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-pho...

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Published in:	Veterinary research (Paris) Vol. 43; no. 1; pp. 60 - 197
Main Authors:	Robert-Tissot, Céline, Rüegger, Vera L, Cattori, Valentino, Meli, Marina L, Riond, Barbara, Moore, Peter F, Engels, Monika, Franchini, Marco, Hofmann-Lehmann, Regina, Lutz, Hans
Format:	Journal Article
Language:	English
Published:	London BioMed Central 20.08.2012 BioMed Central Ltd BMC
Subjects:	Animals B cells Caliciviridae Cat Diseases - immunology Cat Diseases - prevention & control Cat Diseases - virology Cats Cell Line Cell Proliferation Coronaviridae epithelial cells Feline leukemia virus Flow Cytometry - veterinary Gene expression Gene Expression Regulation gene targeting Genetic aspects Health aspects Herpesviridae Immune response immunity Immunity, Innate Immunology Infection Leukocytes, Mononuclear - immunology Male Medicine Medicine & Public Health Microbiology mononuclear leukocytes Myxovirus Resistance Proteins - genetics Myxovirus Resistance Proteins - metabolism Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - pharmacology Oligonucleotides Parvoviridae pathogens Phosphates Physiological aspects Random Allocation Real-Time Polymerase Chain Reaction - veterinary Retroviridae Species Specificity subcutaneous injection Veterinary Medicine/Veterinary Science Virology Virus Diseases - immunology Virus Diseases - prevention & control Virus Diseases - veterinary Virus Diseases - virology Virus Replication viruses Viruses - classification Viruses - immunology Switzerland Feline Cell Viral Inhibition Assay Vesicular Stomatitis Virus Proviral Load CrFK Cell
ISSN:	1297-9716, 0928-4249, 1297-9716
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Abstract	Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae , Herpesviridae , Caliciviridae , Parvoviridae , and Retroviridae . Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro . Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.
AbstractList	Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections. Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections. Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae , Herpesviridae , Caliciviridae , Parvoviridae , and Retroviridae . Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro . Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections. Abstract Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.
Audience	Academic
Author	Engels, Monika Franchini, Marco Hofmann-Lehmann, Regina Moore, Peter F Rüegger, Vera L Robert-Tissot, Céline Meli, Marina L Riond, Barbara Lutz, Hans Cattori, Valentino
AuthorAffiliation	1 Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland 2 Department of Pathology, Microbiology and Immunology, 3315 Vet Med 3A, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA 3 Institute of Virology, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 266a, 8057, Zürich, Switzerland
AuthorAffiliation_xml	– name: 3 Institute of Virology, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 266a, 8057, Zürich, Switzerland – name: 1 Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057, Zurich, Switzerland – name: 2 Department of Pathology, Microbiology and Immunology, 3315 Vet Med 3A, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA
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Keywords	Feline Cell Viral Inhibition Assay Vesicular Stomatitis Virus Proviral Load CrFK Cell
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SubjectTerms	Animals B cells Caliciviridae Cat Diseases - immunology Cat Diseases - prevention & control Cat Diseases - virology Cats Cell Line Cell Proliferation Coronaviridae epithelial cells Feline leukemia virus Flow Cytometry - veterinary Gene expression Gene Expression Regulation gene targeting Genetic aspects Health aspects Herpesviridae Immune response immunity Immunity, Innate Immunology Infection Leukocytes, Mononuclear - immunology Male Medicine Medicine & Public Health Microbiology mononuclear leukocytes Myxovirus Resistance Proteins - genetics Myxovirus Resistance Proteins - metabolism Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - pharmacology Oligonucleotides Parvoviridae pathogens Phosphates Physiological aspects Random Allocation Real-Time Polymerase Chain Reaction - veterinary Retroviridae Species Specificity subcutaneous injection Veterinary Medicine/Veterinary Science Virology Virus Diseases - immunology Virus Diseases - prevention & control Virus Diseases - veterinary Virus Diseases - virology Virus Replication viruses Viruses - classification Viruses - immunology
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Title	Stimulation with a class A CpG oligonucleotide enhances resistance to infection with feline viruses from five different families
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