Malignant Catarrhal Fever of Cattle Is Associated with Low Abundance of IL-2 Transcript and a Predominantly Latent Profile of Ovine Herpesvirus 2 Gene Expression

Background: Malignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. Ovine gamma herpesvirus 2 (OvHV-2) is a causative agent of MCF, which may trigger the disease throug...

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Bibliographic Details
Published in:PloS one Vol. 4; no. 7; p. e6265
Main Authors: Meier-Trummer, Claudia S, Rehrauer, Hubert, Franchini, Marco, Patrignani, Andrea, Wagner, Ulrich, Ackermann, Mathias
Format: Journal Article
Language:English
Published: United States Public Library of Science 15.07.2009
Public Library of Science (PLoS)
Subjects:
Abundance
Algorithms
Analysis
Animal tissues
Animals
Antigens
Apoptosis
Bioinformatics
Biosynthesis
Bovidae
Cattle
CD4 antigen
CD4-CD8 Ratio
CD4-positive T-lymphocytes
CD8 antigen
CD8-positive T-lymphocytes
Cell activation
Cell proliferation
Cytotoxicity
Deoxyribonucleic acid
disease resistance
DNA
DNA microarrays
Fever
Gene expression
Gene Expression Profiling
Genes
Genes, Viral
genetics
Genomes
Genomics
Herpesvirus
immune response
immunology
Inflammation
Interleukin 2
Interleukin-2 - genetics
Latency
Latency-associated nuclear antigen
Lymph nodes
Lymphocytes
Lymphocytes T
Malignant Catarrh
Malignant Catarrh - immunology
Malignant catarrhal fever
messenger RNA
microarray technology
MicroRNAs
Necrosis
Oligonucleotide Array Sequence Analysis
Open reading frames
Ovine gammaherpesvirus 2
Ovine herpesvirus 2
Pathogenesis
Peripheral blood
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Rhadinovirus
Rhadinovirus - genetics
RNA, Messenger
RNA, Messenger - genetics
Sheep
Transcription
Transcription (Genetics)
Vasculitis
Virology
Virology/Effects of Virus Infection on Host Gene Expression
Virology/Host Antiviral Responses
Virus Latency
Viruses
United States > US
California
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Background: Malignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. Ovine gamma herpesvirus 2 (OvHV-2) is a causative agent of MCF, which may trigger the disease through immunopathogenic pathways. Lymphocytes are the main target of the virus. However, the pathogenic basis of the disease is still mysterious. Methods/Findings: We hypothesized that the gene expression patterns of OvHV-2 and the relative abundances of host cell transcripts in lymphnodes may be used to identify pathways that help to explain the pathogenesis of MCF. Therefore, viral and host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Two regions on the viral genome were transcriptionally active, one encoding an orthologue to the latency-associated nuclear antigen (ORF73) of other gamma herpesviruses, the other with no predicted open reading frame. A vast number of transcripts related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. The ratio between CD4- and CD8-positive T-lymphocytes was decreased in the lymphnodes of animals with MCF compared to healthy controls. In contrast, the same ratio was stable, when peripheral blood lymphocytes were analyzed. Conclusions/Significance: The phenotype of mice with a deficient IL-2-system almost perfectly matches the clinical signs observed in cattle with MCF, which feature a significantly decreased IL-2 transcript abundance, compared to healthy cattle. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process. Therefore, this work opens new avenues for research on MCF.
Bibliography:http://dx.doi.org/10.1371/journal.pone.0006265
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Conceived and designed the experiments: CSMT HR MF MA. Performed the experiments: CSMT MF AP. Analyzed the data: CSMT HR MF MA. Contributed reagents/materials/analysis tools: AP UW MA. Wrote the paper: CSMT HR MF MA. Revised paper: MA CSMT HR MF AP UW.
Current address: Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, California, United States of America
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0006265